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| GENERAL INFORMATION DISEASE INFORMATION | Breast Cancer Breast cancer is the most common cancer in women in the United States. According to the American Cancer Society, it's estimated that About 178,480 women in the United States will be found to have invasive breast cancer in 2007. About 40,460 women will die from the disease this year. Right now there are slightly over 2 million women living in the United States who have been treated for breast cancer. If you're worried about developing breast cancer, or if you know someone who has been diagnosed with the disease, one way to deal with your concerns is to get as much information as possible. In this section you'll find important background information about what breast cancer is and how it develops. Breast cancer is a malignant tumor that grows in one or both of the breasts. Breast cancer usually develops in the ducts or lobules, also known as the milk-producing areas of the breast. Breast cancer is the second leading cause of cancer death in women (after lung cancer). Although African-American women have a slightly lower incidence of breast cancer after age 40 than Caucasian women, they have a slightly higher incidence rate of breast cancer before age 40. However, African-American women are more likely to die from breast cancer at every age. Breast cancer is much less common in males; by comparison, the disease is about 100 times more common among women. The American Cancer Society estimates that in 2007 some 2,030 new cases of invasive breast cancer will be diagnosed among men in the United States. Types of breast cancer There are several different types of breast cancer that can be divided into two main categories - noninvasive cancers and invasive cancers. Noninvasive cancer may also be called "carcinoma in situ." Noninvasive breast cancers are confined to the ducts or lobules and they do not spread to surrounding tissues. The two types of noninvasive breast cancers are ductal carcinoma in situ (referred to as DCIS) and lobular carcinoma in situ (referred to as LCIS). It is known that hormones in a woman's body, such as estrogen and progesterone, can play a role in the development of breast cancer. In breast cancer, estrogen causes a doubling of cancer cells every 36 hours. The growing tumor needs to increase its blood supply to provide food and oxygen. Progesterone seems to cause stromal cells (the woman's own cells to send out signals for more blood supply to feed the tumor. (Source: Dr. V. Craig Jordan, vice president and scientific director for the medical science division at Fox Chase Cancer Center in Philadelphia as quoted in NY Times, Hormones And Cancer: By Gina Kolata, Published: December 26, 2006) Non-invasive breast cancer. The majority of non-invasive breast cancers are DCIS. In DCIS, the cancer cells are found only in the milk duct of the breast. If DCIS is not treated, it may progress to invasive cancer. In LCIS, the abnormal cells are found only in the lobules of the breast. Unlike DCIS, LCIS is not considered to be a cancer. It is more like a warning sign of increased risk of developing an invasive breast cancer in the same or opposite breast. While LCIS is a risk factor for invasive cancer, it doesn't actually develop into invasive breast cancer in many women. Invasive breast cancer. Invasive or infiltrating breast cancers penetrate through normal breast tissue (such as the ducts and lobules) and invade surrounding areas. They are more serious than noninvasive cancers because they can spread to other parts of the body, such as the bones, liver, lungs, and brain. There are several kinds of invasive breast cancers. The most common type is invasive ductal carcinoma, which appears in the ducts and accounts for about 80 percent of all breast cancer cases. There are differences in the various types of invasive breast cancer, but the treatment options are similar for all of them. Not all breast cancers are alike Not all breast cancers are alike - there are different stages of breast cancer based on the size of the tumor and whether the cancer has spread. For doctor and patient, knowing the stage of breast cancer is the most important factor in choosing among treatment options. Doctors use a physical exam, biopsy, and other tests to determine breast cancer stage. Stages of Breast Cancer The most common system used to describe the stages of breast cancer is the AJCC/TNM (American Joint Committee on Cancer/Tumor-Nodes-Metastases) system. This system takes into account the tumor size and spread, whether the cancer has spread to lymph nodes, and whether it has spread to distant organs (metastasis). All of this information is then combined in a process called stage grouping. The stage is expressed as a Roman numeral. After stage 0 (carcinoma in situ), the other stages are I through IV (1-4). Some of the stages are further sub-divided using the letters A, B, and C. In general, the lower the number, the less the cancer has spread. A higher number, such as stage IV (4), means a more advanced cancer. These are the stages of breast cancer: Stage 0 - Stage 0 is carcinoma in situ, early stage cancer that is confined to the ducts or the lobules, depending on where it started. It has not gone into the tissues in the breast nor spread to other organs in the body. Ductal carcinoma in situ (DCIS): This is the most common type of noninvasive breast cancer, when abnormal cells are in the lining of a duct. DCIS is also called intraductal carcinoma. DCIS sometimes becomes invasive cancer if not treated. Lobular carcinoma in situ (LCIS): This condition begins in the milk-making glands but does not go through the wall of the lobules. LCIS seldom becomes invasive cancer; however, having LCIS in one breast increases the risk of cancer for both breasts. Stage I - Stage I is an early stage of invasive breast cancer. In Stage I, cancer cells have not spread beyond the breast and the tumor is no more than 2 centimeters (three-quarters of an inch) across. Stage II - Stage II is one of the following: The tumor in the breast is no more than 2 centimeters (three-quarters of an inch) across. The cancer has spread to the lymph nodes under the arm. The tumor is between 2 and 5 centimeters (three-quarters of an inch to 2 inches). The cancer may have spread to the lymph nodes under the arm. The tumor is larger than 5 centimeters (2 inches). The cancer has not spread to the lymph nodes under the arm. Stage III - Stage III may be a large tumor, but the cancer has not spread beyond the breast and nearby lymph nodes. It is locally advanced cancer. Stage IIIA - Stage IIIA is one of the following: The tumor in the breast is smaller than 5 centimeters (2 inches). The cancer has spread to underarm lymph nodes that are attached to each other or to other structures. The tumor is more than 5 centimeters across. The cancer has spread to the underarm lymph nodes. Stage IIIB - Stage IIIB is one of the following: The tumor has grown into the chest wall or the skin of the breast. The cancer has spread to lymph nodes behind the breastbone. Inflammatory breast cancer [insert link to page on inflammatory breast cancer] is a rare type of Stage IIIB breast cancer. The breast looks red and swollen because cancer cells block the lymph vessels in the skin of the breast. Stage IIIC - Stage IIIC is a tumor of any size. It has spread in one of the following ways: The cancer has spread to the lymph nodes behind the breastbone and under the arm. The cancer has spread to the lymph nodes under or above the collarbone. Stage IV - Stage IV is distant metastatic cancer. The cancer has spread to other parts of the body. Recurrent cancer - Recurrent cancer is cancer that has come back (recurred) after a period of time when it could not be detected. It may recur locally in the breast or chest wall as another primary cancer, or it may recur in any other part of the body, such as the bone, liver, or lungs, which is generally referred to as metastatic cancer. Resources: American Cancer Society Centers for Disease Control and Prevention National Cancer Institute January 2006 How is breast cancer treated? When breast cancer is detected at an early stage of development, a number of effective treatment options are available. A woman and her physician will choose the treatment that is right for her, based on the location and extent of the cancer, her age and preferences, and the risks and benefits of each treatment. The basic treatment choices for breast cancer are surgery, radiation, chemotherapy, and hormonal therapy. Local treatments such as breast surgery and radiation therapy are focused on the breast itself to remove or destroy the cancer cells confined to the breast. Systemic treatments such as chemotherapy and hormonal therapy aim to destroy the cancer cells that may have spread throughout the body. Breast cancer cells can be estrogen receptor positive or estrogen receptor negative. Estrogen receptor positive cells are those that have a protein to which the hormone estrogen will bind. Cancer cells that are ER+ need estrogen to grow, and may stop growing when treated with hormones that block estrogen from binding. Estrogen receptor negative refers to cells that do not have a protein to which the hormone estrogen will bind. Cancer cells that are ER- do not need estrogen to grow, and usually do not stop growing when treated with hormones that block estrogen from binding. Surgery has an important role in breast cancer treatment. Most women have the option to choose between breast-conserving surgery (lumpectomy, plus radiation) or removal of the breast (mastectomy). Clinical trials have proven that both options provide the same long-term survival rates for most types of early stage breast cancer. Lumpectomy removes a small tumor and a margin of normal tissue around the tumor` The surgeon also removes some of the lymph nodes under the arm to find out if the cancer has spread. Lumpectomy followed by radiation therapy to destroy any remaining cancer cells is the standard care. A clinical trial on lumpectomy and radiation is currently underway. Modified radical mastectomy is surgery to remove the entire breast, some of the lymph nodes under the arm, and the lining over the chest muscles. It may be appropriate when the breast tumor is large or if cancer is found in more than one part of the breast. Radical mastectomy involves removal of the breast, chest muscles, and all lymph nodes under the arm. It was the standard treatment many years ago, but it is used now only when a tumor has spread to the chest muscles. Radiation therapy uses high-energy x-rays to destroy cancer cells. It is usually used after lumpectomy to destroy any cancer cells that still may remain in the breast after surgery. It is sometimes used to shrink tumors before surgery. Chemotherapy uses drugs, usually a combination of drugs, that travel through the body to slow the growth of cancer cells or to kill them. Hormonal therapy prevents cancer cells from getting the hormones they need to grow. If a breast tumor relies on the body's natural hormones to grow, it is described as estrogen receptor-positive or progesterone-positive. This means that any cancer cells that remain after surgery may continue to grow when these hormones are present in the body. Hormonal therapy can reduce the amount of the body's natural hormones or block the hormones from reaching any remaining cancer cells. Questions to Ask Your Doctor Learning about the diagnosis and treatment options available may help you to make decisions about your care. The first step in the learning process is a conversation with your physician. Every woman's breast cancer diagnosis is different. What a physician recommends for one woman may not be right for another. Developing a list of questions to ask is a good first start to addressing concerns and getting information. Here is a list of basic questions on advanced breast cancer to get the conversation started. You can easily print this page, which includes space to write down the answers your doctor gives you. ABOUT BREAST CANCER What stage is my breast cancer? What does this mean? What are my chances of responding to treatment? ADVANCED BREAST CANCER Is my breast cancer hormone receptor positive? Why has my breast cancer recurred? Does this mean my treatment will have to change? What are my chances of responding to treatment? TREATMENT OPTIONS What are the treatment options for my stage of breast cancer? Why or why not would these treatments help me? Surgery Radiation Chemotherapy Hormonal therapy Biologically targeted therapy Clinical trial participation What treatment options, oral or injectable, are available for me as an advanced breast cancer patient? What treatment do you feel will work best for me? Why are you recommending this treatment? What are the possible side effects of this treatment? Will it make me feel sick? What kinds of food will help me? Or where can I get advice on meal planning? Will this treatment allow me to continue to be involved in my normal daily activities? If not, would another treatment be better for me so I can remain active? Will the treatment affect my family? What do they need to know? Will the treatment affect my appearance? If so, are there other options that will not change the way that I look? What if my current therapy does not continue to benefit me? Are there any other options? What types of hormonal therapies are available to me? Will it be beneficial? Is there any treatment I could be prescribed that does not have to be taken daily? What are the latest advances in hormonal therapies? How often will I be able to see my health care professional? How will I know if the treatment is working? What are the side effects? How can I manage side effects? What side effects should I tell you about? Will I need follow-up care? OTHER CONSIDERATIONS What studies are currently under way for women with advanced stage breast cancer? Do you recommend a clinical trial for me? How can it help? Where can I get further information on my stage of breast cancer? Where can I find additional support? Please be sure to let your doctor know all the medications (prescription, over-the-counter, and herbal supplements) you currently take. Also, check with your doctor before starting any other medication. One in three of us will get cancer at some point in our lives. Once so feared its name was whispered, the disease is no longer an inevitable death sentence. Today, almost two-thirds of those who develop cancer will still be alive five years later, compared with just half in the 1970s. Cancer has turned out to be tougher to crack than everyone hoped when US President Richard Nixon launched the War on Cancer in 1971. But death rates are falling, thanks to earlier detection of tumours and improved use of existing treatments - mainly chemotherapy and radiotherapy. The success has been biggest for children: since the mid-1970s, death rates from cancers of childhood have halved. Of those with the most common childhood cancer, acute lymphocytic leukaemia, 85% are still alive five years later, compared with just 53% in the 1970s. Inner workings A key reason why cancer patients are living longer, is that scientists now understand more clearly what happens when cells turn cancerous. Cancer begins when genes which normally control cell division, growth and repair are damaged through mutation. These genes can then cause cells to grow and divide uncontrollably, destroying neighbouring healthy cells. For example, a gene called p53, which normally acts as a brake on cell division, turns out to be mutated or lost in about half of all tumours. Another proto-oncogene, Myc normally helps healthy cell division, but can become an oncogene if damaged, causing cells to divide unchecked. Mutations can arise by chance errors in DNA replication, and genes can also be damaged by carcinogens - such as tobacco chemicals, benzene, possibly acrylamide and some food additives - or ultraviolet light from sunshine. Certain viruses can also trigger gene mutations, such as the human papilloma virus that can cause cervical cancer. Some mutated genes are inherited: two examples are BRCA1 and BRCA2, which together account for about 5% of all breast cancer cases. Other genes such as DBC2, EMSY and FA have been implicated in ovarian, breast and lung cancer. Once a cell has turned cancerous, it divides until a mass of cells forms a tumour. Diagnostic tests can quickly distinguish between malignant, or cancerous, tumours and those that are benign, or harmless. As a malignant tumour progresses, cells or clumps of cells break off and spread, or metastasise, around the body via the lymphatic system and blood vessels. The latest generation of treatments exploit our knowledge of what happens within cancerous cells. These target proteins and messenger chemicals - such as growth factors or enzymes - that the errant cells need to survive and grow. Glivec (or Gleevec), for example, targets abnormal proteins that help cancerous cells to grow. Dubbed the first "magic bullet" for cancer, it is used to treat one type of leukaemia and a rare cancer of the gut. Another drug, 17AAG, targets cancer cells by suppressing Hsp90 - a protein vital for their growth. The drug is undergoing trials to treat melanoma and other cancers that affect the prostate, kidney and breast. An alternative approach is to persuade the immune system to attack tumours, using vaccines, biological therapies such as alpha interferon or interleukin 2 and genetically altered white blood cells. In the future, scientists hope to target stem-cell-like cells within cancers that may be responsible for most of the growth of some tumours, and evade existing drugs. They also plan to use nano-drugs, nano-bullets and "smart bombs" to deliver molecules with pinpoint precision to tumour cells. Even soil-living or flesh-eating bacteria, engineered viruses, weed extracts, microwaves, chemicals from Antarctic sea squirts and the immune cells of siblings have been recruited to destroy tumours. Prevalence Patterns In developed countries, the cancer most likely to afflict you is non-melanoma skin cancer, often caused by the Sun’s harmful ultraviolet rays. This is usually treated and cured. Melanoma, a deadlier skin cancer, is less common but is increasing by around 3% a year in the US. Though UV light is the cause of many skin cancers, there is some evidence that small amounts may also help prevent other cancers. In the developing world the most common cancers are linked to infectious agents, such as cervical cancer or liver cancer, caused by hepatitis B. The biggest killer in industrialised nations remains lung cancer. For men, lung cancer mortality has been falling since 1990, mirroring a peak in popularity of smoking during the 1960s. For women, who commonly took up smoking later, lung cancer mortality is still rising. Tobacco is also rapidly becoming the leading cause of cancer in Asia. Breast cancer accounts for almost one in three of all cancers diagnosed in women each year. For men, prostate cancer is just as common, with the highest rates in African American men and Caribbean men of African origin. Screening for both of these diseases has improved sharply. Early breast tumours show up on a mammogram long before they can be felt as a lump. More women now survive the disease - three-quarters of women whose breast cancer was diagnosed 10 years ago are still alive today. Similarly, a prostate-specific antigen (PSA) test has revolutionised early diagnosis for this cancer in the US. Some experts argue that screening can be harmful, however. Factoring in risk Dozens of factors affect an individual’s risk of getting cancer. Smoking is the biggest single risk factor - with tobacco linked to about a third of all cancers. Another clearly established risk factor is exposure to ionising radiation. This may be responsible for cancers in people living around Chernobyl in Ukraine, Toikamura in Japan and for people working in nuclear power plants. Radiation may also have led to a high incidence of cancer in those who witnessed early nuclear tests or have been in contact with depleted uranium munitions, though a recent study contests this risk. Risk factors for developing breast cancer include: being childless or delaying childbearing until aged over 30, starting periods early, using hormone replacement therapy, being exposed to oestrogen-like chemicals, and drinking one or more units of alcohol daily. More than one risk factor is usually needed before cancer cells develop. Risks posed by living near overhead power lines or petrol stops, or using cellphones, are less clear. Preventative steps If everyone stopped smoking, cancer deaths could be cut by one-third, researchers estimate. Moves to protect people from passive smoking, in bars for example, are gaining ground in many industrialised countries. Staying out of sunlight and using strong sunscreens could prevent hundreds of thousands of us from developing skin cancer worldwide annually. Foods rich in antioxidants and beneficial fatty acids such as omega-3 and oleic acid found in olive oil - a key ingredient of the healthy Mediterranean diet - seem to protect against some cancers, although the findings are mixed. Doctors can increasingly intervene directly to prevent cancers. For example, vaccines against hepatitis B could soon cut deaths from liver cancer. There are also preventive therapies - such as tamoxifen or the trial drug anastrazole - that interfere with the production of the hormone oestrogen, implicated in many breast cancers. Doctors believe that it could halve the rates of breast cancer in women with a family history of the disease. All this means that, while hopes of total cure for cancer are still unrealistic, the disease is increasingly under control. https://www.cancercenter.com/popup-chat.cfm chat live with someone about your type of cancer Call 800-641-9710 anytime ------------------------------------------------------------------------------------------ Breast cancer cells have to learn to walk before they can run Medical Research News Published: Wednesday, 2-Jan-2008 Early-stage breast cancer that has not yet invaded the surrounding tissues may already contain highly motile cells, bringing the tumor one step closer to metastasis, report researchers at the Salk Institute for Biological Studies. Their study, published in the Dec. 30 issue of the Journal of Cell Biology, suggests that these cells, although not yet invasive, could wander off along milk ducts and seed new tumors within the same breast. "A lack of invasion suggested a lack of motility," says lead author Gray Pearson, Ph.D, a postdoctoral researcher in the Molecular and Cell Biology Laboratory at the Salk, "but that's not so." "This is an exciting finding because it suggests that cells might acquire migratory properties much earlier than expected," says senior author Tony Hunter, Ph.D., a professor in the Molecular and Cell Biology Laboratory. Due to improved screening programs, most breast tumors are discovered at an early stage when they are still small and confined. In such cases, cancer cells have not grown into the surrounding tissues and remain within the borders of a duct, the most common site where invasive breast cancer arises. These tumors are known as DCIS (ductal carcinoma in situ). The standard treatment for DCIS is lumpectomy, the surgical removal of the tumor and surrounding tissue. Approximately 16% of DCIS patients treated with lumpectomy alone develop recurrent breast cancer growth within 5 years of treatment. One of the questions faced by oncologists and patients is whether they should add gamma radiation after undergoing surgery to catch straying tumor cells and reduce the risk of recurrent breast cancer. Currently, the decision is based solely on the size of the tumor. "Our findings suggest that, if a DCIS contains these highly motile cells, the patient may have an increased risk for recurrent growth," says Pearson. "Under these circumstances you would consider adding radiation treatment regardless of tumor size." While the presence of highly motile cells may guide treatment decisions in the future, the researchers have yet to show that wandering cells do indeed influence a patient's outcome, cautions Pearson. In their study, the Salk researchers used a tissue culture model that recreates the duct of the mammary gland. They embedded human cells, isolated from breast tissue, in a three- dimensional matrix that mimics their natural surroundings. These cells spontaneously develop into so called acini, hollow structures resembling tiny milk ducts. Then they turned on the ERK1/2 MAP kinase pathway, a signaling cascade frequently activated during the development of tumors, and watched in real time as breast cancer cells learned how to walk. "We quickly realized that there was a significant cell movement, which was quite surprising," recounts Pearson. "Within 24 hours, a large number of these spheres had lost their organization, and the cells started to dance around." (see movie) While dangerously invasive cells can squeeze through the basement membrane and make a run for the surrounding tissue, motile cells still could not escape the confines of the ERK-activated acini. "But the acquisition of motility prior to invasion presumably lowers the barrier for future invasive growth," explains Pearson. "The advent of live-cell imaging allows us to watch labeled cells move around in tissues and learn a lot about their behavior, which wouldn't be revealed in cultured cells," says Hunter. With the next step, Pearson hopes to identify molecular markers for breast cancer cell motility that will help oncologists to diagnose patients who are at higher risk of metastasis. http://www.salk.edu/ -------------------------------------------------------------------------------------------- Dear OncoLink "Ask The Experts," I read that chemotherapy can cause a Pap smear to be abnormal. How long should I wait to get a Pap after my last chemotherapy treatment for breast cancer (AC-T)? Could radiation have an affect also? Christina S. Chu, MD, Assistant Professor of the Division of Gynecologic Oncology at the University of Pennsylvania Health System, responds: I am unaware of any effect of chemotherapy on Pap tests, specifically any direct effect of chemotherapy drugs that would cause abnormal Pap smears. However, patients who are immunosuppressed for long periods of time because of maintenance chemotherapy may conceivably be more prone to abnormal Paps, just as any other immunosuppressed patients are (such as patients with organ transplants or HIV). Radiation therapy to the pelvis or vagina can certainly affect Pap tests, but radiation to the breast would not be expected to cause Pap test abnormalities. I believe that it should be fine to get a Pap test once you have completed treatment and have recovered from any immediate treatment-related side effects http://www.oncolink.org/experts/article.cfm?c=3&s=16&ss=34&id=2354 ----------------------------------------------------------------------------------------------- ------------------- Public release date: 29-Feb-2008 Contact: NCI Press Officers ncipressofficers@mail.nih.gov 301-496-6641 NIH/National Cancer Institute New study of targeted therapies for breast cancer -- model for global clinical trials Two targeted medications designed to treat an aggressive form of breast cancer are being tested in a new study involving 8,000 participants in 50 countries across six continents -- a clinical trial that investigators hope will provide a new model for global cancer research. This trial, dubbed ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study), will be one of the first global initiatives in which two large, academic breast cancer research networks covering different parts of the world have jointly developed a study in which all care and data collection are standardized, regardless of where patients are treated. The networks are The Breast Cancer Intergroup of North America (TBCI), based in the United States, and the Breast International Group (BIG) in Brussels, Belgium. TBCI consists of six National Cancer Institute (NCI)-funded clinical trials cooperative groups. NCI is part of the National Institutes of Health. ALTTO is designed to answer the most pressing questions regarding use of two widely used cancer agents: whether one agent is more effective, which agent is safer for patients, and what benefit will be derived by taking the drugs separately, in tandem order, or together" The trial is a randomized, Phase III study, which is considered a gold standard method for proving drug effectiveness. The two agents tested in ALTTO are drugs designed to treat HER2-positive tumors, which is a particularly aggressive form of cancer that affects approximately 20 percent to 25 percent of breast cancer patients. Both agents, trastuzumab (Herceptin) and lapatinib (Tykerb), have already been approved by the U.S. Food and Drug Administration for use for treatment of HER2-positive breast cancer. ALTTO will provide the first head-to-head comparison of trastuzumab and lapatinib in the earliest, most treatable stages of cancer. It will also be one of the first large-scale studies to evaluate lapatinib’s effectiveness in treating early breast cancer. HER2-positive breast cancer is caused by an excess of HER2 genes or by over-production of its protein, the HER2 cell surface receptor. Trastuzumab consists of large antibodies that once injected into patients, latch on to the portion of the HER2 protein that sits on the outer surface of the cancer cell whereas lapatinib acts by entering a cancer cell and binding to the part of the HER2 protein that lies beneath the surface of the cell. The trial is unusual in that it has two different designs depending on whether patients with stage I or stage II breast cancer have already been treated with chemotherapy. The study thus will compare four different regimens of targeted therapy administered over a 52-week period. Patients will be randomized to receive either trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib, or the two treatments in combination. “There have been major improvements in the management of patients with early breast cancer in the last few years, so this new study builds on this knowledge and sets an example of the new era: good science, good worldwide collaboration,” said Edith Perez, M.D., an oncologist in the North Central Cancer Treatment Group (NCCTG) at Mayo Clinic in Jacksonville, Fla., who will lead the study for TBCI. “It may be that using two treatments that work in different ways against HER2-positive breast cancer offers a complementary strategy that is more powerful than either drug alone.” ALTTO will be one of the first trials of its scope in which translational research -- taking science from bench to bedside -- plays a critical role, investigators say. In ALTTO, biological material will be collected from thousands of patients in order to determine a tumor profile that responds best to the drugs -- information that could lead to individualized patient care and, possibly, to development of next generation agents. “The difference between this study and many that came before it is that the collection of biological materials occurs as the trial is being conducted, not as an afterthought. While there are exceptions, not many companies or organizations have been willing to invest in that kind of research before,” said Martine J. Piccart, M.D., Ph.D., professor of oncology at the Université Libre de Bruxelles, Belgium, and lead investigator for BIG, which she founded in 1996. “Now we have the chance to optimize therapy with powerful drugs in order to provide the best treatment possible for each of our patients.” Perez and Piccart led the development team of the ALTTO trial and will act as the study’s co- principal investigators. On behalf of BIG and TBCI, these two lead investigators have been working toward collaborative clinical studies for a number of years. The ALTTO study, they say, represents a new paradigm that blends the high standards of both systems in order to test the latest breast cancer treatments as efficiently as possible in thousands of women worldwide. "The NCI greatly appreciates the work that Mayo Clinic, TBCI and BIG are doing to help advance our understanding of the complex mechanisms that underlie different types of breast cancer,” said Jo Anne Zujewski, M.D., a senior investigator in the clinical investigations branch at NCI. “We hope that this model of international collaboration is one which we can build upon in the future." Lapatinib, in combination with the chemotherapy drug capecitabine, was approved by the U.S. Food and Drug Administration in March 2007 for the treatment of advanced or metastatic HER2-positive breast cancer in patients who had received prior therapy with three agents -- an anthracycline, a taxane and Herceptin. GlaxoSmithKline is providing the study drug, as well as additional financial support for the ALTTO trial. All drugs carry potential side effects, and more information of side effects for lapatinib and trastuzumab can be found in the Q&A at http: //www.cancer.gov/newscenter/pressreleases/ALTTOQandA. NCI and GSK also provided comment and input on the design of the study. NCCTG will act as the treatment base for ALTTO in North America. BIG is a network of 41 non-U.S. research groups from around the world. Its Brussels-based BrEAST Data Center is providing centralized data management for the global study (including the United States). The other members of TBCI include the Eastern Cooperative Oncology Group (ECOG), the Cancer and Leukemia Group B (CALGB), the Southwest Oncology Group (SWOG), the American College of Surgeons Oncology Group (ACOSOG), and the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). To date, more than 300 centers around the world have enrolled patients into ALTTO. Full enrollment is expected to involve about 500 centers in the United States and more than 800 centers in Europe and the rest of the world. A complete listing of ALTTO participating sites can be found by searching for ALTTO at http://clinicaltrials.gov. ### A Science Writer’s seminar on International Breast Cancer Trials and ALTTO will take place on Friday, February 29, 2008 in New York City. To register for the seminar, please call (301) 496-6641 or go to www.videocast.nih.gov to view a Webcast of the event. For Broadcasters: Video soundbites from the lead investigators are available through Pathfire’s Digital Media Gateway (DMG) or on the Web at www.TheNewsMarket.com. On the DMG main page, look for the Mayo Clinic branded page in the left navbar, or click on the VNF Master Locator and search for mayoclinic0078. If you have questions or problems in locating the story, contact Pathfire Customer Support at 888-345-0489. If you do not have access to Pathfire’s DMG, and would like access to Mayo Clinic’s video resources by satellite or other means, please call 507-538-0492. For a Q&A on this trial, please go to http://www.cancer. gov/newscenter/pressreleases/ALTTOQandA. For Spanish translations of the press release and Q&A, please go to http://cancer. gov/espanol/noticias/ALTTOSpanishRelease. For more info on BIG, please go to http://www.breastinternationalgroup.org. For more info on Mayo, please go to http://clinicaltrials.mayo.edu or contact the Mayo Clinic Cancer Center Clinical Trials Referral Office at 507-538-7623. For more information about cancer, visit http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4 CANCER. *********************************************************************** ** Law.com Jury Awards $12 Million in Breast Cancer Case Friday February 29, 3:02 am ET Shannon P. Duffy, The Legal Intelligencer A Philadelphia jury on Wednesday awarded $12 million to a woman with terminal breast cancer in her suit against two doctors for allegedly failing to diagnose the disease before it had progressed to an incurable stage. Plaintiffs attorney Donna Lee Jones of Saltz Mongeluzzi Barrett & Bendesky said one of the doctors had settled confidentially prior to trial, and that the jury concluded that the settling doctor was 35 percent responsible for the failure to diagnose. As a result, Jones said, plaintiff Angela Sutherlin stands to recover 65 percent of the verdict, or $7.8 million, from the nonsettling doctor, Arthur D. Magilner, and the Fox Chase Cancer Center. The case is Sutherlin v. Magilner. The verdict was handed up by a unanimous 12-member jury after a weeklong trial before Philadelphia Common Pleas Judge Nitza I. Quinones Alejandro. According to court papers, Sutherlin had a screening mammography in June 2003 in a Fox Chase mobile unit. The suit alleged that, due to Sutherlin's history of breast problems, including a bloody discharge from her nipple that required a prior biopsy, she was not a proper candidate for a "screening" test in the mobile unit and instead should have undergone a "diagnostic" test. Magilner testified in his deposition that Sutherlin's questionnaire, which was completed by Fox Chase technicians, made no mention of Sutherlin's surgical history, nor the fact that she had undergone breast reduction surgery in 2000. The suit alleged that Magilner's report erroneously described a "dilated duct" that was "unchanged" and suggested a follow-up test in one year. But Jones argued in court papers that a comparison of Sutherlin's 2001 and 2003 mammograms showed that the report from the first test made no mention of a dilated duct. "In short, Dr. Magilner missed a clear opportunity to note the change in the left ductal prominence, which is where Angela Sutherlin ultimately developed a palpable lump and breast cancer was found," Jones wrote in her pretrial memo. The suit alleged that when Sutherlin had another mammogram in March 2004 at the Albert Einstein Medical Center, another doctor, Susan Summerton, interpreted the films and noted "several small nodular densities," but found that they "remain stable compared to prior studies." But the suit alleged that no nodular densities had been noted in the prior report, and that Summerton therefore should not have labeled the finding as benign. In court papers, Jones argued that "like Dr. Magilner the previous year, Dr. Summerton missed the opportunity to timely diagnose Angela Sutherlin's breast cancer at a time when it was still Stage I and curable with a complete, simple mastectomy." Jones said Summerton and Albert Einstein Medical Center had settled prior to trial. At trial, Barry Singer, the plaintiff's expert oncologist, testified that Sutherlin's cancer was the type that went from Stage I directly to Stage IV. According to court papers, Sutherlin's surgery was unsuccessful, because the cancer had metastasized to her bones and organs. Jones told the jury that Sutherlin is currently receiving only palliative care, but that the high-dose narcotics cannot control her excruciating pain. Magilner was defended at trial by attorneys Dean F. Murtagh and Chilton G. Goebel III of German Gallagher & Murtagh. In an interview, Murtagh said he was disappointed by the verdict and that he believed his client had a strong defense. In her pretrial memo, Jones had demanded $2 million to settle the suit -- the combined limit for the two doctors' insurance policies -- and warned that "if a jury verdict is rendered, it will well exceed these policy limits, and expose the carriers for Dr. Magilner and Dr. Summerton to claims of bad faith." In an interview, Jones said that Magilner and Fox Chase had offered $125,000 to settle the case and never increased that offer during the trial. Go to Law.com for legal information and services on the web ------------------------------------------------------------------------------------ Breast cancer gene carriers need dual screening By Anthony J. Brown, MD Tue Feb 26, 9:05 PM ET NEW YORK (Reuters Health) - Among women with BRCA1 gene mutations, which are known to increase the risk of breast cancer, annual screening with both mammography and MRI is associated with better survival when compared with screening with either method alone, new research indicates. The trade-offs, however, are a high rate of false-positive results, which lead to unnecessary biopsies. The findings were based on data from 22 studies that included 8,139 women who carried the BRCA1 gene. In addition, the researchers developed a prediction model based on data from the Surveillance Epidemiology and End Results (SEER) Program (1975-1980) and the Breast Cancer Surveillance Consortium. The results indicated that annual combined screening with mammography plus MRI increased the average life expectancy by 1.38 years compared with follow-up only without screening tests (clinical surveillance). The false-positive rate was 84.0 percent. "For women who carry BRCA1 gene mutations, adding annual MRI to annual mammography has a clear benefit in terms of projected life expectancy and breast cancer mortality reduction," lead author Dr. Janie M. Lee told Reuters Health. "Whether the trade-offs related to MRI screening are acceptable to women at increased risk of developing breast cancer is still being investigated." In the general population, the lifetime risk of breast cancer for women is 13 percent. In BRCA1 mutation carriers, by contrast, this risk can be as high as 80 percent. Strategies to reduce this high risk have included preventative mastectomy, removal of the ovaries (to lower levels of estrogen which can encourage breast cancer growth), preventive chemotherapy, and more frequent office visits, according to the report in the journal Radiology. Younger women, especially those of childbearing age, are often reluctant to undergo preventative mastectomy, the investigators point out. Preventative chemotherapy might be a suitable choice, but unfortunately no studies to date have shown it to reduce breast cancer mortality. That leaves increased surveillance. According to the report, mammography is not nearly as sensitive at detecting breast cancers in BRCA1 mutation carriers as it is in the general population. Previous research has shown that MRI can achieve higher sensitivity than mammography, but whether this translates into reduced breast cancer mortality is unclear. Due to the long length of follow-up and the large number of patients required, the authors note that it is unlikely that any trial will ever investigate whether MRI screening can reduce breast cancer mortality. This prompted Lee, from Massachusetts General Hospital in Boston, and colleagues to conduct the current decision analysis. The average life expectancy was 71.15 years, the report indicates, and with clinical surveillance alone, the average diameter of breast cancers at diagnosis was 2.6 centimeters. Using annual screening with mammography, MRI, or both, the average tumor diameter at diagnosis fell to 1.9, 1.3, and 1.1 centimeters, respectively. Compared with clinical surveillance, all three imaging-based screening strategies increased life expectancy and reduced mortality from breast cancer. Again, the most pronounced benefit was with mammography plus MRI. In addition to the high false-positive rate seen with mammography plus MRI screening, nearly one in three women underwent one or more biopsies for what turned out to be benign disease. The false-positive rates and negative biopsy results with the other screening strategies were also increased, but not as high as that seen with the combined approach. More research is required to find the optimal sequence and frequency for screening tests for breast cancer, and to "minimize the potentially negative effects on women's health-related quality of life when screening with increased intensity is pursued," Lee noted. She added that her team is "currently working to extend our model of breast cancer natural history and screening in BRCA1 gene mutation carriers to women who carry BRCA2 mutations, and women whose lifetime risk of breast cancer exceeds 20 percent -- these women are defined by the American Cancer Society as being at 'high-risk' of developing breast cancer." SOURCE: Radiology, March 2008. ----------------------------------------------------------------------------------------- Cost of Breast Cancer Can Include Paycheck Tue Feb 26, 5:01 PM ET TUESDAY, Feb. 26 (HealthDay News) -- In the first year after being diagnosed with breast cancer, working women lose an average of 27 percent of their income, a new study finds. Researchers from Laval University in Quebec interviewed 829 women at one, six and 12 months after their breast cancer diagnosis. The women were asked a number of work-related questions, such as their working status before their diagnosis, the amount of time absent from work due to the disease, and types of compensation received during their work absences. The women were also asked about their perceptions of their financial status, and whether it had changed for the worse at one year after breast cancer diagnosis. Of the 800 women who completed all three interviews, 459 had paying jobs at the time of their diagnosis and 403 of those women had work absences or reduced work hours after their diagnosis. On average, these women lost 27 percent of the wages they would normally have earned if they hadn't been ill, even after all forms of compensation were taken into account. Ten percent of the women lost more than two-thirds of their income. The study found wide variation in the percentage of lost wages. Those most likely to suffer a large loss of income were: less educated; lived farther from the hospital where they had their cancer treatment; had more serious disease; required chemotherapy; or were self-employed, worked part time, or recently hired at their job. "These findings should sensitize clinicians to the real extent to which wage losses resulting from breast cancer can substantially and negatively affect the financial situation of working women and their families," the study authors wrote. The study was published in the Feb. 26 online issue of the Journal of the National Cancer Institute. More information The American Cancer Society offers tips for coping with breast cancer. ----------------------------------------------------------------------------------------------- --- Hormone therapy skews breast cancer diagnosis By Andrew Stern Mon Feb 25, 5:37 PM ET CHICAGO (Reuters) - Women on hormone replacement therapy have only a slightly higher risk of developing breast cancer, but there are much greater chances they will experience the worry of abnormal mammograms or may undergo an avoidable breast biopsy, researchers said on Monday. Mammograms and biopsy exams were also found to be less reliable at detecting breast cancer among women taking hormones, which counteract symptoms of menopause such as hot flashes and vaginal dryness. Originally, the 2002 Women's Health Initiative study involving 16,608 women aged 50 to 79 found breast cancer incidence among women taking the hormones estrogen and progestin projected to an additional one in 1,000 cases compared to women taking an inert placebo. "What this data does is emphasize that yes, the breast cancer risk is still there, but more importantly, instead of that low number of one in 1,000 getting breast cancer, one in 10 women are told they had an abnormal mammogram they'll have to deal with, and probably even more importantly, one in 25 women will have an otherwise avoidable breast biopsy," Dr. Rowan Chlebowski at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center said in a telephone interview. "Both of those less reliably found cancer," he added. Previous research has shown hormone replacement therapy increases breast tissue density, which can make detection of cancerous tumors more difficult, although the current study did not examine this factor. Since the original findings of increased cancer risk, doctors generally have urged women opting for hormone therapy to use it at the lowest effective dose for the shortest possible time. Roughly 25 million U.S. prescriptions for hormone therapy are written yearly, Chlebowski said. The pharmaceutical company Wyeth said in a statement the study's findings did not change what is already known about the breast cancer risk from hormone replacement therapy. DOCTOR'S ADVICE "These findings represent a concern for post-menopausal women who are considering hormone therapy," Chlebowski said in a statement. "They should take the results of this study into consideration and consult with their physicians before undergoing even short-term hormone therapy." In the study published in the Archives of Internal Medicine, 35 percent of women taking hormones had mammograms with abnormal results compared to 23 percent of women taking a placebo. An abnormal test can create emotional as well as financial hardships, the study noted. Ten percent of women taking hormones had breast biopsies ordered by their doctors, compared to 6 percent of women taking a placebo. During the 5-1/2 years of the study, there were 199 breast cancers found in the hormone group and 150 in the placebo group. Women taking hormones had more advanced cancers yet biopsies ordered by their doctors had a lower rate of diagnosis -- 15 percent in the hormone group versus 20 percent in the placebo group. "(A year) after discontinuation (of the therapy) ... the adverse effects on mammogram and breast biopsy performance were seen even in younger women in the fifth decade of life, so the finding may impact women just entering menopause as well," Chlebowski said. (Editing by Eric Walsh)http://news.yahoo. com/s/nm/20080225/ts_nm/cancer_breast_hormones_dc_2 ---------------------------------------------------------------------------------------- Thursday February 28, 03:02 PM Plastic a big worry for cancer researchers Plastic which surrounds us in our daily lives may contribute to New Zealand's high rate of cancer, particularly breast cancer, says a visiting medical expert. Dr Karin Michels, an associate professor in the Department of Epidemiology at Harvard University in Massachusetts, will not eat food wrapped or stored in plastic, nor will she use a plastic shower curtain. Dr Michels, who is visiting New Zealand as guest of the Breast Cancer Research Trust as part of her research into the causes of breast cancer in women, said she and her research colleagues were "really concerned" about plastics and plasticisers used in every day life in many countries. "The plastic bottles we drink from, especially these hard plastic bottles which are reusable, the Tupperware, the baby bottles where we heat up the milk and shower curtains -- all release substances that screw up our hormone system." She said heating lunch in a plastic container in a microwave released substances into the food which entered the body. "You eat these substances that screw up your hormonal system and that has been associated with an increased risk of breast cancer in animals." The substances could also be breathed in when they were released from shower curtains during a hot shower. She said studies had yet to be done on humans because humans could not be fed carcinogenic substances. "But you can feed it to rats and if you give it to rats, they develop breast cancer." Dr Michels said heating plastic caused substances, including the carcinogenic substance, bisthenol A, to be released in greater quantities than eating food stored or wrapped in unheated plastic. "You are exposed to these kind of substances almost everywhere. If you wrap your food in plastic wrap it gets into the food. "It is particularly bad for babies because the baby's small, and you heat up the milk in a plastic body and all that stuff gets into the formula. "The baby gets all these chemicals and who knows what it does to the baby? We don't really know but it is something we are extremely concerned about." Bisthenol A was the substance that most concerned the medical research industry. She said the substances still came out of the plastic even when it was not heated. "It is a very scary thought." Dr Michels said the increasing use of plastic, such as plastic jars in supermarkets was not a good practice. "Good old glass is probably better." She said the potential risk from plastic had only been discovered recently but was hard to study because plastic was so widely used. New Zealand had one of the highest rates of breast cancer in the world. Dr Michels said breast cancer was the most common form of cancer in the world and one in seven women got breast cancer. "That's very scary. We know it is lifestyle but we don't seem to be able to eliminate it or reduce it." In New Zealand it killed more than 600 women a year Dr Michels said many woman gained weight after menopause and that also contributed substantially to their risk of breast cancer. Part of her research into breast cancer was to look at the relationship between diet and the disease. She said while the research had yet to identify the risk factors in breast cancer from food, alcohol had been identified as a risk. "Alcohol consumption like a glass of wine a day already increases your risk of breast cancer by 20 percent." That risk could be countered with a daily folate or B vitamin pill. A low-fat diet and regular exercise for young girls may also lower the cancer risk factor. She said diet before puberty could also affect the risk rate for breast cancer although the research in that area was still very preliminary and more was needed. A high birth weight also increased the risk factor for breast cancer, but the risk factors from the time of conception to puberty or early adulthood had not been considered. "That is something we have totally missed out on before for many years, almost decades, that we have done epidemiologic research which is the research that identifies risk factors for breast cancer." Dr Michels said the rise in the rate of breast cancer must be attributed to lifestyle and environment because women who moved from a country with a low rate of breast cancer to a country with a high rate, adopted the cancer rate of their new country. "It must be lifestyle. It is not genetic," she said. --------------------------------------------------------------------------------- Press Release Source: Interactive Supercomputing Northeastern University and Mass General Hospital Increase the Accuracy, While Reducing the Diagnosis Time, for Breast Cancer Detection Tuesday February 26, 9:00 am ET Research teams solve the computational hurdle using Star-P WALTHAM, Mass., Feb. 26 /PRNewswire/ -- Researchers at the Northeastern University Computer Architecture Research Lab (NUCAR) and the National Science Foundation's (NSF) Center for Subsurface Sensing and Imaging Systems (CenSSIS) are teaming with Massachusetts General Hospital (MGH) on a promising new breast cancer detection technology that improves breast cancer screening accuracy. The team is applying new supercomputing technology to a 30-year-old imaging modality called tomosynthesis, which until now has been relegated to research labs due to its massive and expensive computational requirements. Called Digital Breast Tomosynthesis (DBT), the system creates a 3D image of the breast using a series of x-ray projections collected during a 20- second, 40-degree sweep. It makes cancer lesions easier to detect among dense breast tissue by creating a stack of 1mm spaced high- resolution slices that can be displayed individually, or assembled into a 3D view that can be rendered for more careful examination. DBT also reduces the amount of breast compression required by traditional mammography, which can deter women from getting an annual screening. NUCAR scientists addressed this computational hurdle by creating a DBT reconstruction application on their desktop PCs using MATLAB®, and then running the code on an affordable Linux parallel cluster using Star-P software from Interactive Supercomputing, Inc. (ISC). Reconstructing DBT used to take many hours. With this new Star-P approach, imaging reconstruction can be completed in just a few minutes. The complicated parallel programming task has been dramatically simplified using Star-P, slashing development time from many months to days. General Electric is developing a commercial DBT device that should be generally available in 2009. The Northeastern team has been supported by a NSF Small Business Technology Transfer (STTR) project with ISC, the NSF's CenSSIS, and by Mass General Hospital, which is known worldwide for offering the most advanced breast screening and treatment services available. "The support from Northeastern has radically shifted this paradigm," said Richard Moore, program director for Breast Imaging Research and CenSSIS at MGH. "With this kind of performance, we can realistically rely on 3D methods that were out of the question previously. It's not just the speed, it's the exploratory freedom." "We've been able to take a technology that had an enormous computational barrier and turn it into a commercially viable product by making its underlying parallel computing platform fast, easy and affordable," said Professor David Kaeli, director of NUCAR and thrust leader in CenSSIS. "The multi-dimensional imaging technique involves the processing of up to 15 high resolution x-ray images. This kind of application typically requires a very long time to carry out repetitive operations on large image matrices. Parallelizing these large datasets on affordable hardware can now achieve the performance required for real-world implementations." The parallelization effort was performed by Dana Schaa, a graduate student working with Professor Kaeli. Kaeli said Star-P was a good solution for this challenge because it enabled his team of researchers to easily code algorithms using their familiar desktop environment, automatically transforming the application to run on parallel clusters. Star-P eliminates the need to re- program the applications in complex languages such as C, FORTRAN or MPI (message passing interface) to run on the cluster -- which otherwise requires arcane programming knowledge and months to complete. About Interactive Supercomputing Interactive Supercomputing (ISC) launched in 2004 to commercialize Star-P, an interactive parallel computing platform. With automatic parallelization and interactive execution of existing desktop simulation applications, Star-P merges two previously distinct environments - desktop computers and high performance servers - into one. Based in Waltham, Mass., the privately held company markets Star-P for a range of biomedical, financial, and government laboratory research applications. Star-P is a registered trademark of Interactive Supercomputing Inc. All other trademarks mentioned herein are the property of their respective owners. Contacts: Ilya Mirman Michelle Dillon Interactive Supercomputing Beaupre & Co. Public Relations 781-419-5088 603-559-5835 --------------------------------------------------------------------------------------------- FDA clears Avastin for breast cancer By MATTHEW PERRONE, AP Business Writer Fri Feb 22, 6:30 PM ET WASHINGTON - A Genentech drug received federal approval on Friday to treat breast cancer, a surprise decision that could represent a shift in standards for assessing the effectiveness of cancer medicines. Going against the recommendation of its advisory panel, the Food and Drug Administration judged the effectiveness of Avastin based on measurements of tumor growth, not patient survival. The ruling prompted a mixed reaction from both doctors and advocates for breast-cancer patients. Some bemoaned the lowering of medical standards, but others applauded the federal government's endorsement of a drug that is already prescribed "off-label" to an estimated 9,500 patients and for whom insurance coverage is limited. Avastin, which is already approved in the U.S. for treating lung and colon cancer, was Genentech's best-selling product last year with revenue of $2.3 billion. Through a partnership with Genentech, Swiss drug maker Roche markets the drug in Europe, where it had previously been approved as a breast-cancer treatment. Shares of Genentech Inc. rose $5.76, or 8 percent, Friday to $77.36 in after hours trading. FDA approval for drugs targeted at cancer patients who have never been treated before is usually contingent upon data showing a drug extended, or improved the quality of, patients' lives. Avastin showed neither in a study submitted by Genentech, though the drug did slow tumor growth. Wall Street analysts believe FDA's Avastin decision opens the door for more cancer drugs to be approved for their tumor-shrinking capabilities — a trend that worries some health experts. "If FDA sets a precedent of approving a drug based on progression free survival, people are afraid they may stop looking at survival as the most important endpoint," said Dr. Kay Dickersin, director of the Center for Clinical Trials at Johns Hopkins University. In December, a panel of outside FDA advisers voted 5 to 4 against Genentech's application, indicating the drug's benefits did not outweigh toxic side effects. Nevertheless, U.S. doctors continued prescribing it "off-label," or without a federal endorsement. Some insurers are reluctant to pay for Avastin's use among breast-cancer patients, which can cost $100,000 for a year's supply. Dr. Joseph Sparano of Montefiore Medical Center in New York said he prescribes Avastin because it has shown better results at slowing breast cancer growth than any other drug on the market. The Y-ME National Breast Cancer Organization said the approval gives patients an important new option. "The benefits we're looking at here matter because they give patients hope," said Margaret C. Kirk, the group's chief executive. "Without disease progression they may survive to see a discovery that can help them." they may survive to see a discovery that can help them." But the president of the National Breast Cancer Coalition said the decision marked a lowering of standards for FDA. She argued that the drug's effectiveness should not have outweighed safety risks, pointing to six deaths attributed to the drug in the study submitted to FDA. "All they had was progression-free survival in one trial, no increase in quality of life and patient deaths in the Avastin group," said Fran Visco. "We're very confused why FDA made this decision." First approved in the U.S. to treat colon cancer in 2004, Avastin was the first drug to fight cancer by blocking nutrients from reaching tumors. ------------------------------------------------------------------------------------------ Catholics asked to stop Komen donations By JON GAMBRELL, Associated Press Writer Tue Feb 26, 11:24 PM ET LITTLE ROCK, Ark. - The Diocese of Little Rock is urging its members not to donate to a breast cancer foundation known for its fundraising races across the globe because the group supports Planned Parenthood. The diocese says the Susan G. Komen for the Cure foundation, which has invested about $1 billion in cancer outreach and research, gives money to Planned Parenthood to hold breast exams and offer education to women in its clinics. "Donors cannot control how an organization designates its funds," a diocese statement reads. "Therefore, money donated for a specific service ... directly frees up funds to support other areas of an organization's agenda." Marianne Linane, director of the diocese's "respect life" office, said those other agendas includes abortions and contraceptive services. The Catholic church's policy is that abortion is wrong in every instance. Linane said the Little Rock diocese, which oversees all churches in Arkansas, used the same statement sent out by the church's St. Louis diocese last year. However, the end of the Little Rock letter included addresses of Arkansas hospitals parishioners could donate to that would eliminate "the administrative funds for a middle broker." Monsignor J. Gaston Hebert sent the statement to parishes and Catholic schools this month and planned to send out a follow-up letter, Linane said. Hebert did not return a call for comment Tuesday. Little Rock follows other dioceses in raising concerns with the foundation. In 2005, the Roman Catholic Diocese of Charleston abandoned its support of the foundation, while in 2006 the newspaper of the Catholic Diocese of Phoenix took issue over Komen's Planned Parenthood funding. Rebecca Gibson, a spokeswoman for the Komen foundation, said the group invested $69.6 million in more than 1,600 community-based education and screening programs during 2007. Planned Parenthood received less than 1 percent of that money, she said. "It's insignificant in relation to all of the funding we do," Gibson said. "I think it's just really unfortunate undue attention is being shed on organizations that are providing vital services in those communities." The diocese's decision comes as northwest Arkansas prepares for its running of the Race for the Cure on April 19. Officials estimated Little Rock's running last year brought out more than 43,000 participants and raised more than $1.65 million. ___ On the Net: Susan G. Komen for the Cure: http://www.komen.org/ Diocese of Little Rock: http://www.dolr.org ------------------------------------------------------------------------------------------- HRT Can Lead to Abnormal Mammograms, Biopsies By Amanda Gardner HealthDay Reporter Mon Feb 25, 5:03 PM ET MONDAY, Feb. 25 (HealthDay News) -- Women who take combined hormone therapy for about five years have a higher risk of abnormal mammograms and breast biopsies. This, in turn, may decrease the effectiveness of these methods of detecting breast cancer, according to a new study published in the Feb. 25 issue of Archives of Internal Medicine. "Women need to be aware of the risks, and it's not just risk of increased breast cancer. It's a risk of possibly having abnormal mammograms and really being tortured by them," said Dr. Kristin Byrne, chief of breast imaging at Lenox Hill Hospital in New York City, who was not involved with the study. "It's a whole slew of things they need to be aware of before making a decision to go on hormone therapy." Study lead author Dr. Rowan Chlebowski, a medical oncologist with the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, said that for women with severe menopausal symptoms, the new findings "won't be an issue." "It [hormone-replacement therapy] is safer than we thought maybe a year and a half ago," he said. "Certainly, no one is going to brush off a breast biopsy. But for women trying to decide whether to start on hormone therapy or who want to see if their symptoms get better, they have to think about whether they would mind having a call back" for a mammogram. The landmark Women's Health Initiative (WHI) study found that combined estrogen plus progestin hormone replacement therapy (HRT) increased the risk of breast cancer. One recent study indicated that the risk was greater for lobular breast cancer than ductal carcinoma malignancy. Since 2003, there has been a decline in breast cancer incidence that coincided with a decline in HRT use for menopausal symptoms. Nevertheless, Chlebowski pointed out, "a lot of people are still using hormone therapy." For the new study, the authors looked at 16,608 women who participated in the WHI from 1993 to 1998. The women were randomly assigned to receive combined hormone replacement therapy (estrogen plus progesterone) or a placebo. Mammograms and breast exams were conducted annually and biopsies performed, if indicated. More than one in 10 women had otherwise avoidable mammogram abnormalities (an increase of 11 percent), while one out of 25 women had otherwise avoidable breast biopsies (an increase of 4 percent), after taking the hormone therapy for five years. Ten percent of women in the HRT group had to have a biopsy, compared to 6.1 percent in the placebo group. Yet the biopsies only detected 14.8 percent of cancers in the HRT group, compared with 19.6 percent in the placebo group. "Your breasts become denser [with HRT], and we all know that mammography isn't as sensitive for the detection of breast cancer in women with dense breasts," Byrne explained. The increase in abnormal mammograms persisted for at least 12 months even after discontinuing hormone therapy, the study found. For the medical community, Chlebowski said, this finding "focuses attention that diagnosis is hindered. We have additional imaging modalities, and maybe we should evaluate them to see if we can get rid of this hindrance or delay in diagnosis. It hasn't been a factor for attention before, but it probably should be." Chlebowski has consulted for several pharmaceutical companies. A prepared statement from Wyeth Pharmaceuticals, which makes the hormonal product Prempro, said: "This study looks at data first reported in 2002 which showed an increase in the number of repeat mammograms and breast biopsies related to the use of estrogen combined with progestin. Current labeling for all hormone therapy products provides information about breast cancer risks, abnormal mammograms and guidance regarding yearly breast examinations by a healthcare professional. "While use of estrogen combined with progestin increased the need for repeat mammograms in this study, nearly one in four women in the placebo group also needed repeat mammograms due to abnormalities. The findings in this report do not change what we already know about the benefits and risks of hormone therapy," the statement said. More information For more on the Women's Health Initiative, visit the U.S. National Heart, Lung, and Blood Institute. ---------------------------------------------------------------------------------------- Cut-Off Cancer Patient to Get $9M By THOMAS WATKINS,Associated Press Writer AP - Sunday, February 24LOS ANGELES - A woman who had her medical coverage canceled as she was undergoing treatment for breast cancer has been awarded more than $9 million in a case against one of California's largest health insurers. ADVERTISEMENT Patsy Bates, 52, a hairdresser from Lakewood, had been left with more than $129,000 in unpaid medical bills when Health Net Inc. canceled her policy in 2004. On Friday, arbitration judge Sam Cianchetti ordered Health Net to repay that amount while providing $8.4 million in punitive damages and $750,000 for emotional distress. "It's hard to imagine a situation more trying than the one Bates has had to endure," Cianchetti wrote in the decision. "The rug was pulled out from underneath, and that occurred at a time when she is diagnosed with breast cancer, one of the leading causes of death for women." Bates, a mother of two, said she screamed when she heard about the damage award. "I am elated," she said. Bates' attorney William Shernoff said he wanted other insurers to take notice of the award. "We are going to put a stop to this practice," he said. Health Net said it was implementing a freeze on policy cancelations that would last until the company sets up a third-party review panel to scrutinize cases. "Obviously we regret the way that this has turned out, but we are intent on fixing the processes to maintain the public trust," spokesman David Olson said. The award came a day after the Los Angeles city attorney sued Health Net, claiming it illegally canceled the coverage of about 1,600 patients. City Attorney Rocky Delgadillo also said the company illegally ran an incentive program in which it paid bonuses to an administrator for meeting targets of policy cancelations. Health Net acknowledged that such a program existed in 2002 and 2003 but was subsequently scrapped. "It's hard to imagine a policy more reprehensible than tying bonuses to encourage the recision of health insurance that helps keep the public well and alive," Cianchetti wrote in the Bates decision. Bates had been insured with another company but was persuaded to switch over to a Health Net policy after an agent suggested she could save money. She said she had undergone surgery to remove a tumor and had received her first two chemotherapy treatments when doctors stopped treating her because her bills were going unpaid. "I was devastated. I didn't know what was going to happen," Bates said. "It's boggling that someone can do that to you." Bates went on to complete her cancer treatment through a state-funded program. Health Net also said it would review its practices and the way its brokers and agents are trained. -------------------------------------------------------------------------------- Saturday February 23, 11:49 AM Diet tied to breast cancer risk A new study suggests that women who eat diets rich in meat and dairy may have a decreased risk of breast cancer, while those who bulk up on fibre, fruits and vegetables show a lower risk of ovarian cancer. The findings, published in the International Journal of Cancer, add to questions surrounding the role of diet in women's risk of the cancers. High alcohol intake has been consistently linked to breast cancer risk, but when it comes to other facets of the diet, studies have yielded conflicting results, according to the researchers on the current work, led by Dr Valeria Edefonti of the University of Milan. Some studies, for example, have found that women who eat a lot of red and processed meat are more likely to develop breast cancer than other women; but other studies have found no such link. Saturated fat, found mainly in animal products, has been tied to higher breast cancer risk in some studies, but not in others. While many of these studies have looked at single nutrients or food groups, another way to address the question is to look at dietary patterns - the combination of nutrients and foods that a person tends to favour. For their study, Edefonti and her colleagues assessed dietary patterns among 3,600 women with either breast or ovarian cancer, and 3,413 healthy women of the same age. Using detailed dietary questionnaires, the researchers identified four common dietary patterns in the study group: an "animal product" pattern, which was heavy in meat and saturated fat, but also zinc, calcium and certain other nutrients; a "vitamins and fibre" pattern, which besides fibre was rich in vitamin C, beta-carotene and other nutrients found in fruits and vegetables; an "unsaturated fat" pattern that contained high amounts of vegetable and fish oils, as well as vitamin E; and a "starch-rich" pattern high in simple carbohydrates, vegetable protein and sodium. Overall, the study found, women who followed a pattern rich in vitamins and fibber had a 23 percent lower risk of ovarian cancer than women who consumed the lowest amounts of those foods and nutrients. On the other hand, the animal-product pattern was linked to a similar reduction in breast cancer risk. Women who followed the unsaturated-fat pattern had a slightly reduced risk of breast cancer, while the starch-rich diet was tied to elevated risks of both cancers. It's not yet clear what to make of the findings, in part because they show associations between dietary patterns and cancer risk - and not that the foods directly affect cancer development. In terms of general health, experts usually recommend limiting red meat and saturated fat, while eating more fruits, vegetables, whole grains and sources of "good" unsaturated fat - like fish, nuts and olive oil. SOURCE: International Journal of Cancer, February 2008. --------------------------------------------------------------------------------------- Press Release Source: Diane Connolly-Zaniboni Breast Cancer Research Fund 3,000 ''Cure Breast Cancer'' License Plates Now on the Road in Massachusetts Wednesday February 20, 12:52 pm ET BOSTON--(BUSINESS WIRE)--It was October 31, 2006 when the “Cure Breast Cancer” license plate first became available in the Commonwealth. Since then, over 3,000 people have signed up for this license plate, raising more than $100,000 for research to find a cure for breast cancer. This amount will only get exponentially larger thanks to the efforts of Deb McNeill, Janice Connolly-Laubenstein and others who have spear-headed the plate initiative. The special license plate, designed by McNeill, costs an additional $40 above the regular registration Registry fee. Of that $40, $12 goes to the Registry of Motor Vehicles for production with the remaining $28 deposited in the Diane Connolly-Zaniboni Breast Cancer Research Fund at Tufts New England Medical Center in Boston. The plate is renewed every two years, at which point $40 goes directly into to the breast cancer research fund. Deb McNeill, a breast cancer survivor herself, is thrilled that the dream of a breast cancer license plate has finally come true. “Each plate sold represents a personal, unique story,” said McNeill. “It represents a community of supporters who have stepped up and made a statement to help the fight against breast cancer. These individuals and the stories they share is what makes all of our hard work worthwhile.” McNeill is not alone in her belief that this plate has helped support both breast cancer survivors and the loved ones of those impacted by this disease. As supporters register for their “Cure Breast Cancer” plates, they offer their stories and the personal connections to the cause. Plate 280 writes: “I lost my 47-year-old sister Judy on May 24th of this year to breast cancer. I miss her very much… She was my only sister. I feel in my heart that getting a plate is something I can do for the cure of breast cancer.” Plate 436 writes: “My mother was diagnosed with breast cancer in April of 1996, one month before my wedding. She went on to have 5 years cancer free. Her cancer returned in July of 2001, when my sister and I were both 6 months pregnant. She lived until June of 2003, fighting for every day to spend with her grand babies. I miss her terribly…” Plate 1409 writes: “As a daughter of a breast cancer survivor and having lost two close friends to this disease, I am honored to display this plate on my car.” The breast cancer license plate honors so many people who have lost their battle with breast cancer, including the late Diane Connolly-Zaniboni. The license plate with a pink ribbon and the word “Cure” serves as a symbol of hope, strength and support to those currently suffering from the disease. To get your plate go to your local Registry of Motor Vehicles or order online at: http://www. mass.gov/rmv/express/cureBreastCancer.htm Contact: For Diane Connolly-Zaniboni Breast Cancer Research Fund Deb McNeill, 781-820-0199 -------------------------------------------------------------------------------- Source: Diane Connolly-Zaniboni Breast Cancer Research Fund ----------------------------------------------------------------------------------------------- -- Press Release Source: Hologic, Inc. Three Year Analysis of Treatment Efficacy, Cosmesis, and Toxicity Support use of the Hologic Mammosite Radiation Therapy System Monday February 25, 4:00 pm ET American Society of Breast Surgeons Study Represents Largest Patient Population to Date BEDFORD, Mass., Feb. 25 /PRNewswire-FirstCall/ -- Hologic, Inc. (Nasdaq: HOLX - News) a diversified medical technologies company specializing in imaging systems, diagnostics, and interventional devices dedicated to serving the healthcare needs of women, today announced the publication of a study evaluating the Hologic MammoSite® Radiation Therapy System (RTS), one-, two- and three-years after treatment. The study by Frank A. Vicini, M. D., and others, published in the February 15, 2008, issue of Cancer(1), the peer- reviewed professional journal of the American Cancer Society, reports on treatment efficacy, cosmetic results and toxicities of patients enrolled in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial. The American Society of Breast Surgeons MammoSite Registry(2) includes a total of 1,440 patients with early stage breast cancer, who were undergoing breast-conserving therapy and were treated with MammoSite RTS between May 2002 and July 2004. Of the total, 87 percent of the patients had invasive breast cancer and 13 percent had been diagnosed with ductal carcinoma in situ (DCIS). The authors presented a subset analysis of the first 400 cases enrolled in the study with a median follow-up of 37.5 months. The three-year actuarial rate of local or regional recurrence was less than 2 percent in this group. The percentage of breasts with good and/or excellent cosmetic results was 93 percent at 36 months. The authors also reported a three-year actuarial local control rate of 100 percent in the first 48 patients enrolled with DCIS. An analysis of the overall registry population with a median follow-up of 30.1 months, showed a two-year actuarial rate of local or regional recurrence of 1.0 percent; good and/or excellent cosmetic results of 94 percent at 24 months and a 10.6 percent rate of symptomatic seromas. The authors note that the MammoSite Radiation Therapy System is "logistically simpler, technically more reproducible, and patient 'friendly'" than other interstitial brachytherapy devices. The authors go on to say that "These results demonstrate that treatment efficacy, cosmesis, and toxicities 2-years and 3-years after treatment with APBI [Accelerated Partial Breast Irradiation] using the MammoSite device in this registry trial are similar to those reported with other forms of APBI with similar follow-up." "The American Society of Breast Surgeons Registry represents the largest patient population treated with the MammoSite Radiation Therapy System," said Ellen Sheets, M.D., Chief Medical Officer for Hologic. "We are very encouraged by these results and believe they support the clinical benefits of this unique technology." The MammoSite device is a balloon catheter that is inserted into the cavity created by a lumpectomy (the surgical removal of a breast tumor). MammoSite RTS delivers radiation from inside the lumpectomy cavity over a course of five days. The device targets radiation to the area where tumors are most likely to recur, while reducing exposure to healthy tissue. Since its introduction in 2002, more than 38,000 breast cancer patients have received partial breast irradiation utilizing the MammoSite RTS. A copy of the study may be downloaded by going to the web site below: http://www3. interscience.wiley.com/cgi- bin/abstract/117880284/ABSTRACT?CRETRY=1&SRETRY=0 About Hologic, Inc. Hologic, Inc. is a leading developer, manufacturer and supplier of premium diagnostics, medical imaging systems and surgical products dedicated to serving the healthcare needs of women. Hologic's core business units are focused on breast health, diagnostics, GYN surgical, and skeletal health. Hologic provides a comprehensive suite of technologies with products for mammography and breast biopsy, radiation treatment for early-stage breast cancer, cervical cancer screening, treatment for menorrhagia, osteoporosis assessment, preterm birth risk assessment, and mini C-arm for extremity imaging. For more information visit www.hologic. com. Forward Looking Disclaimer This News Release contains forward-looking information that involves risks and uncertainties, including statements about the effect of the use of Hologic's MammoSite Radiation Therapy System on breast cancer patients. There can be no assurance that the effects demonstrated in the study described herein will be replicated in any particular manner with respect to an individual patient as the actual effect of the use of Hologic's MammoSite Radiation Therapy System on patients with breast cancer can only be determined on a case-by-case basis depending on the particular circumstances of the patient in question. Hologic expressly disclaims any obligation or undertaking to release publicly any updates or revisions to the data or statements presented herein to reflect any change in Hologic's expectations or any change in events, conditions or circumstances on which any such data or statements are based. Certain factors that could adversely affect Hologic's business and prospects are described in Hologic's filings with the Securities and Exchange Commission. 1 Frank Vicini, M.D., Peter D. Beitsch, M.D., F.A.C.S., Coral A. Quiet, M.D., Angela J. Keleher, Delia Garcia, M.D., Howard C. Snider Jr, Mark A. Gittleman, M.D., Victor J. Zannis, M.D., Henry M. Kuerer ,M.D., Ph.D., Maureen Lyden, Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI), Cancer, 2008;112(4),758 766 2 The MammoSite Breast Brachytherapy Trial was supported in part by a grant from Cytyc (Hologic). Co-authors Victor J. Zannis and Maureen Lyden received support from Cytyc (Hologic). Contact: Frances Doria Jim Culley Director, Investor Director, Strategic Relations Projects Hologic, Inc. Hologic, Inc. Tel: 781.999.7377 Tel: 781.999.7583 Source: Hologic, Inc. --------------------------------------------------------------------------------------- Study debunks personality link to breast cancer Tue Jan 29, 2008 4:11pm ET By Will Dunham WASHINGTON (Reuters) - The idea that a woman's personality traits can make her more prone to get breast cancer appears to be nothing more than a myth, according to a Dutch study that tested the notion. Women who were unemotional, depressed or anxious were no more or less likely to get breast cancer than any other women, the study found. Nor were women who were optimistic, angry or understanding, or had any combination of personality traits. The Dutch researchers measured 11 personality traits in 9,705 Dutch women in a survey in 1989 and 1990, then tracked them through 2003 to see who got breast cancer. "The present results indicate that women should not worry about a possible impact of personality factors as a risk factor for breast cancer," Eveline Bleiker of the Netherlands Cancer Institute and Antoni van Leeuwenhoek Hospital in Amsterdam, who led the study, said by e-mail. "Moreover, women with breast cancer should not worry that their character might have contributed to the development of their disease," Bleiker added. Bleiker noted that some researchers in the 1980s advanced the idea of a "cancer-prone" personality with such traits as stoicism and difficulty in expressing emotions. "The earlier studies had a number of methodological flaws," Bleiker said, adding that more recent, large studies have not found the existence of a "cancer-prone" personality. "In summary, there is currently no convincing evidence that such a personality profile exists," Bleiker said. Continued... --------------------------------------------------------------------------------------- Surgeons' Characteristics Influence Breast Cancer Care Gender, race, schooling influence likelihood of giving radiation, study says TUESDAY, Jan. 29 (HealthDay News) -- Individual surgeon characteristics, such as gender and medical training, may influence whether a women receives radiation after breast conservation cancer surgery, a U.S. study suggests. Many breast cancer patients don't receive radiation therapy after breast conservation therapy, even though it's been shown to reduce breast cancer recurrence and is considered a standard of quality care, according to background information in the study. Previous research has shown that certain patient characteristics, such as race and distance from a radiation therapy facility, influence the likelihood of receiving radiation after breast cancer surgery. But the effect of doctor characteristics has been unclear. In this study, published in the Jan. 29 online issue of the Journal of the National Cancer Institute, researchers at the Herbert Irving Comprehensive Cancer Center at Columbia University in New York City analyzed data on about 30,000 women, 65 and older, who were diagnosed with breast cancer between 1991 and 2002 and received breast-conservation surgery. The researchers also looked at the 4,453 surgeons who operated on the women. About 75 percent of the women in the study received radiation after surgery and, each year from 1991 to 2002, there was an increase in the percentage of women who received radiation. But older women, black women, unmarried women and those living outside urban areas were less likely to receive radiation. After they adjusted for patient and tumor characteristics, the study authors concluded that women who received radiation were more likely to have a surgeon who was female, had an M. D. degree (compared to a D.O. degree), or was trained in the United States. "Our study is one of the first to demonstrate associations between certain surgeon characteristics and quality of breast cancer care. If confirmed, more research is needed on whether they reflect surgeon behavior, patient response, or physician-patient interactions," the researchers wrote. ----- Breast cancer drugs increase heart risk slightly NEW YORK (Reuters Health) - Aromatase inhibitors, a class of drugs used to ward off the recurrence of breast cancer after surgery, increase the risk of cardiovascular disorders slightly more than does treatment with tamoxifen, a new study shows. Aromatase inhibitors are superior to tamoxifen in some circumstances, the researchers point out in the medical journal Cancer, but previous reports have suggested a trend toward increased cardiac events in association with their use. To look into this, Dr. Federica Cuppone from Regina Elena National Cancer Institute, Rome, and colleagues analyzed data from seven studies involving a total of nearly 20,000 postmenopausal women with early breast cancer. After follow-up periods ranging from about 2 years to 5 years, there was a small 31 percent relative increase From Medscape Hematology-Oncology Talking With Your Patients About Cancer What Patients Need to Know About Hot Flashes Posted 02/27/2008 Charles L. Loprinzi, MD Author Information Editor's Note: Hot flashes are an inevitable part of life for most women as their ovaries stop producing estrogen, their menstrual periods diminish, and they become menopausal. In women with breast cancer, hot flashes may be more severe and frequent than in women without breast cancer, largely due to the various treatments used for treating the breast cancer. For the most part, however, the efficacy of treatments for hot flashes in patients with breast cancer is similar to that in women without breast cancer. Although estrogen-based therapy has been standard treatment and perhaps still the most effective therapy for hot flashes, most physicians are reluctant to give estrogen to women with breast cancer. Ongoing study of nonhormonal treatments has shown the benefit of several treatment approaches, including some newer antidepressants and an antiseizure drug; alternative therapies have undergone considerable study, but efficacy claims are largely unsubstantiated by reliable clinical trials. For a woman with breast cancer, discussion about hot flashes and their management typically takes place with her oncologist. According to Charles L. Loprinzi, MD, Professor of Oncology at the Mayo Clinic College of Medicine in Rochester, Minnesota, an expert on this topic, oncologists have a responsibility to talk to their breast cancer patients about treatment options for hot flashes. In a recent interview with Mary Beth Nierengarten, MA, on behalf of Medscape, Dr. Loprinzi addressed some of the common concerns of patients with breast cancer in regard to hot flashes and currently available treatments. Ms. Nierengarten: Most women experience hot flashes as a normal symptom of menopause. Are hot flashes different in women with breast cancer? Dr. Loprinzi: Hot flashes are a major problem for many women as they go through the menopausal period. The reason women experience hot flashes is because the ovaries cease the production of estrogen, which eventually leads to the cessation of menstrual periods. This is normally a relatively slow process that begins around the age of 50 years and occurs over a few years, but it can vary from age 45 to 60. In many women with breast cancer, hot flashes can be even more of a problem than for those without breast cancer because some of the treatments used to treat breast cancer can cause an abrupt or premature menopause. Chemotherapy or ovarian suppression treatments (either removing the ovaries or suppressing their function through medical means) can cause this menopause. For example, a 35-year-old woman who has had her ovaries removed usually will have a lot of trouble with hot flashes. Administration of the antiestrogen agent tamoxifen or an aromatase inhibitor can also lead to hot flashes. In postmenopausal women who start tamoxifen, hot flashes are more common among those who had substantial difficulty with hot flashes at the time of menopause or who had been taking estrogen replacement therapy. Premenopausal women tend to have less trouble with hot flashes while receiving tamoxifen and their hot flashes are often temporary. Ms. Nierengarten: Why are hot flashes more of a problem in women who undergo an abrupt ending of their menses? Dr. Loprinzi: During a natural menopause, hormone concentrations in the blood usually decrease somewhat gradually over the course of months to a few years. An abrupt cessation of hormone concentrations in the blood seems to lead to more severe symptoms. What occurs in men is similar. Men usually do not experience hot flashes because they typically do not have abrupt decreases in testosterone blood concentrations; rather, they very gradually decrease over time. However, when testosterone concentrations are abruptly lowered, as occurs when men are treated for prostate cancer, hot flashes may be a substantial problem. Ms. Nierengarten: How are hot flashes measured in your studies? Dr. Loprinzi: In all of our studies, patients keep track of their hot flashes for a week, using a daily diary to record how many hot flashes they have every day. We also ask them to grade the severity of the hot flashes on a scale of 1-4, with 1 being mild, 2 moderate, 3 severe, and 4 very severe. Then we can either determine the frequency by just counting the number of hot flashes per day, or develop a hot flash score using both the frequency and the severity rating. For example, a person who records 10 hot flashes a day and labels their severity as 3 will have a score of 30. If you look at the results of these studies graphically, you almost always see that the decrease in hot flash frequency from baseline is the same as the decrease in the hot flash score. This tells me that the hot flash frequency and severity generally go hand in hand. Ms. Nierengarten: For how long a period do hot flashes typically last? Dr. Loprinzi: On average, hot flashes last for 3-4 years. However, 15% of women will have them for 10-15 years or longer. On the other hand, some women will not experience hot flashes at all. Ms. Nierengarten: As a medical oncologist, how did you develop an interest in studying hot flashes? Isn't this an issue usually evaluated by gynecologists or endocrinologists? Dr. Loprinzi: Hot flashes are a substantial problem in patients with a history of breast cancer. Two decades ago, when we first started studying hot flashes in these patients, physicians were wary of using estrogen therapy in this population and therefore denied them what was the most effective therapy for hot flashes. At that time, there was less concern about the use of estrogen in women who did not have a history of breast cancer, and there was not much effort to find nonestrogenic means of treating hot flashes. Thus, my colleagues and I started to look at nonestrogenic therapies for hot flashes for our patients with breast cancer. Ms. Nierengarten: What are some of the nonestrogenic therapies used to treat hot flashes in women with breast cancer? Dr. Loprinzi: One of the nonestrogenic therapies that we have studied, although still a hormonal therapy, is progesterone.[1-4] Before discussing the results of studies with progesterone and other agents, it is worth noting that there is about a 25% reduction of hot flashes among those who receive a placebo when data after 4 weeks of treatment are compared with those from the baseline week. Megestrol acetate was the first progesterone that we studied, administered orally at low doses. About an 85% reduction of hot flashes was demonstrated with this drug. In another study, a single intramuscular injection of medroxyprogesterone acetate reduced hot flashes by 80% to 85% for at least 6 weeks. This is a progesterone agent that has a relatively long half-life. Despite these drugs being very effective for decreasing hot flashes, many physicians are afraid to prescribe any hormones for a person with breast cancer. Although there is some rationale for why progesterone alone might cause breast cancer-related problems, there is also a rationale for why it might be safe to administer progesterone hormones without concurrent estrogen. One reason is that we've used these drugs over the years to treat breast cancer. Ms. Nierengarten: Do you recommend hormonal therapies for hot flashes in your patients with breast cancer? Dr. Loprinzi: After discussing the potential risks and benefits, I am often willing to provide hormonal therapies as an option for patients with breast cancer. If a woman does not have breast cancer or has hormone receptor-negative breast cancer, then short-term use of hormonal therapy is a reasonable option. In that situation, I like to administer a single intramuscular injection of medroxyprogesterone acetate because it can last for a relatively long time. If a woman is hormone receptor-positive, I talk to her about the pros and cons of hormonal therapy and let her know about other options. Again, I am willing to prescribe hormonal therapy for a patient if she understands the issues. Ms. Nierengarten: Do some women with breast cancer still want hormonal therapy for hot flashes, particularly given the results of the Women's Health Initiative trial[5] that showed an increased risk for breast cancer in women who received hormonal replacement therapy? Dr. Loprinzi: Yes, some women still want to receive hormonal therapy for hot flashes. The Women's Health Initiative trial showed an increased risk for breast cancer in women (none of whom had a history of breast cancer) who received combined estrogen/progestin therapy, but in another arm of the study that included women who did not have their uteruses and who received estrogen alone, the incidence of breast cancer was neutral or even showed a trend toward a decreased risk for breast cancer. On the basis of this study, therefore, there has been concern about the use of combined estrogen/progestin therapy because that is what seems to increase the risk for breast cancer. The women in our progesterone trials did not receive estrogen but progesterone alone. Whether progesterone alone increases breast cancer risk is unknown. Because we really don't know, I tell my patients: "It might have some detrimental effect in terms of breast cancer risk; it might have some beneficial effect; or it might have a neutral effect." Whatever the effect, I think it is small. Ms. Nierengarten: This is still a big question for many women. Dr. Loprinzi: Let me change your word from "big" to "humongous." I would say this is true for physicians as well. However, I think it is a reasonable option to administer progesterone alone. Women certainly don't have to use it, but it works nicely against hot flashes, accepting that there is a potential risk. Ms. Nierengarten: What other types of treatments are available for women who do not want to take hormonal therapy? Dr. Loprinzi: Several newer antidepressants appear to reduce hot flashes. Venlafaxine and paroxetine appear to be the most effective agents, on the basis of results of the currently published studies.[6,7] In our study of venlafaxine, we achieved a 60% reduction in hot flashes using low to intermediate doses, that is, doses that are low compared with those used to treat depression. Similar results were observed with paroxetine, with about a 60% to 70% reduction in hot flashes. Sertraline and fluoxetine do not seem to work as well,[8] and the evidence is still out with regard to citalopram, although it looks promising. New data, published in January 2008, support the efficacy of another antidepressant, desvenlafaxine, in reducing hot flashes. These newer antidepressants do not decrease hot flashes as much as hormones do, but they are better than a placebo. Ms. Nierengarten: Do any of these drugs interfere with breast cancer treatment? Dr. Loprinzi: It is important to know that some of these drugs, such as paroxetine, do interfere with use of tamoxifen. For tamoxifen to be effective, it needs to be converted in the body by an enzyme, CYP2D6. Some drugs inhibit that enzyme, with paroxetine being one of the chief offenders. Sertraline and some of the other antidepressants may inhibit the enzyme to some degree, but all of the answers are not in on that drug. Venlafaxine does not appear to inhibit CYP2D6 to any significant degree. Thus, if a patient is on tamoxifen therapy, she should avoid paroxetine and other drugs that inhibit the CYP2D6 enzyme. Ms. Nierengarten: For how long do patients need to take these drugs? Dr. Loprinzi: The effects of antidepressants on hot flashes usually are apparent within the first 2- 3 weeks. In one of our trials of venlafaxine,[6] patients taking venlafaxine at the lowest dose of 37.5 mg/day had a 40% reduction in hot flashes after 1 week. When we increased the dose to 75 mg/day, a 60% reduction in hot flashes was seen. Patients in the placebo group had only a 27% reduction. No one has actually looked at the best length of time to treat hot flashes. What happens in clinical practice is that after a while, if the hot flashes are controlled, patients will wean themselves off treatment or their physician will help them wean off treatment. That could be a few months, a year, or a few years later. That applies to all treatments. Ms. Nierengarten: What is your experience with patients starting and stopping drugs, such as venlafaxine? Dr. Loprinzi: With venlafaxine, it is important to start at a low dose because it can cause some toxicity -- nausea and vomiting being the most common. About 10% of women cannot tolerate venlafaxine; other women will have initial nausea that ends after about a week even though the drug is continued. When this drug is discontinued, it should be titrated down to the lowest dose. Some patients will have drug withdrawal reactions, even with slow downward titration. Ms. Nierengarten: Are some patients reluctant to take drugs labeled antidepressants? Dr. Loprinzi: Some women don't want to take an antidepressant just as they don't want to take an antiseizure medication. When we first started to use these drugs for the treatment of hot flashes, some said that the only reason they were effective was because they helped with depression. That is not true. The women in our trials did not have clinical depression. In addition, the effect of these agents on hot flashes is much more rapid than on depressive symptoms. Ms. Nierengarten: You mentioned antiseizure medication. Is this an option for the treatment of hot flashes in women with breast cancer? Dr. Loprinzi: Gabapentin, an antiseizure medication that is also used for pain management, is another drug that has efficacy against hot flashes. It is approved by the FDA [US Food and Drug Administration] for the treatment of postherpetic neuralgia and seems to be effective against other types of pain, such as diabetic neuropathy. Randomized controlled trials of gabapentin have shown a 50% to 60% reduction of hot flashes, which is similar to that achieved with antidepressants.[9,10] This drug is pretty well tolerated. Some patients report light-headedness and some swelling. As with the antidepressants, it is necessary to start at a low dose and titrate upward. Although therapy can be initiated at 300 mg/day, the most studied dose is 900 mg/day. Higher doses may be more effective for hot flashes, but this has not yet been established. For people who use gabapentin for pain, doses can be as high as 3000 mg/day. A question that remains to be answered is whether the newer form of gabapentin, pregabalin will also be effective against hot flashes. Studies are under way. Ms. Nierengarten: What about other types of drugs? Dr. Loprinzi: Clonidine, an older drug that historically was used to treat high blood pressure, is the first drug we tested for hot flashes.[11] Clonidine decreases hot flashes by about 40%, so it is generally less effective than the antidepressants or gabapentin. Clonidine works nicely in some women but not in others. That is actually true for all of these agents. Clonidine is not used all that often for a number of reasons: (1) it doesn't work as well as some of the newer drugs, and (2) it has been associated with more side effects, such as dry mouth, sleeping difficulty, and low blood pressure. Ms. Nierengarten: When discussing these treatment options with your patients, do you tell them that it may take trial and error to find the treatment that best suits them? Dr. Loprinzi: Yes, I do. Ms. Nierengarten: What about alternative therapies for the treatment of hot flashes? There is a lot of information in the mainstream media about vitamin E, black cohosh, and soy. This subject can be very confusing for patients. Dr. Loprinzi: One study[12] has examined the effects of vitamin E on hot flashes and has suggested some benefit in terms of a reduction of 1 hot flash per day. Thus, with vitamin E, a person might have the equivalent of the placebo effect, plus a little bit more. We initially thought that vitamin E was well tolerated, but newer information has suggested that it might increase mortality in patients with chronic diseases. Many other alternative therapies have been thought to be helpful and studied, but the claims of benefit have not been substantiated by good studies. In that category are soy products. We conducted one of the first studies on the effects of soy on hot flashes and it was convincingly negative.[13] Most of the other soy studies had the same conclusion. So, at this point in time, no soy product has been clearly demonstrated to be helpful. That does not mean that there might not be some soy product at some time that may be beneficial to some degree. Also in this category is black cohosh, despite the advertisements. The good placebo-controlled trials on black cohosh do not show a benefit in terms of preventing hot flashes.[14] Some published studies do claim a benefit associated with black cohosh, but they are not very good studies. Another alternative therapy thought to play a role in the prevention of hot flashes is acupuncture. There is one published placebo-controlled trial from our group at the Mayo Clinic that did not show a benefit.[15] Ms. Nierengarten: If a patient asks you about using these alternative therapies, what do you say to her? Dr. Loprinzi: One question that I am asked by many patients is whether there is any evidence that these therapies can be harmful. What about soy? The pendulum has swung back and forth. Fifteen years ago there was information suggesting that soy might prevent breast cancer, and that the reason why women in Asia did not develop breast cancer was because of the high level of soy in their diet. Later, other data suggested that soy, because it is estrogenic, increases breast cancer risk. I currently conclude that there is nothing convincing one way or the other. Data are lacking that would make me recommend pharmacologic doses of soy for hot flashes or for breast cancer prevention. On the other hand, if patients like to include soy in their diet, I suspect that that may be better than eating all animal fat, and I don't try to dissuade them. Ms. Nierengarten: Are there any other things that women can do to relieve hot flashes? Dr. Loprinzi: Among the things that women can do is to layer their clothing, use fans to keep the air moving to cool them down, not sleep with too many blankets, and keep their bedroom cooler at night. Other interventions that may be helpful are meditation and hypnosis. Preliminary data show that meditation-type breathing might be helpful, not at the time of a hot flash but once or twice a day on a scheduled basis. I emphasize that this might help prevent hot flashes. Studies are ongoing to try to substantiate this claim. Hypnosis also might be helpful; early data are becoming available, but more definitive data are needed. Ms. Nierengarten: Does having breast cancer change or affect the efficacy of these treatments for hot flashes? In other words, is there a difference in the efficacy of hot flash treatments based on breast cancer status? Dr. Loprinzi: In terms of the efficacy of treatment of hot flashes, it doesn't matter whether a woman has breast cancer. Also, for all practical purposes, it doesn't matter whether a woman is taking tamoxifen.[16] That is not general knowledge and it is not generally accepted, but there is information to support that statement. Ms. Nierengarten: What message would you like to give to other oncologists about talking to their breast cancer patients about hot flashes? Dr. Loprinzi: Hot flashes can be a substantial problem in many women, including patients with breast cancer. A number of therapies do work to reduce hot flashes, including estrogen and progesterone. Nonhormonal therapies, mostly the newer antidepressants and gabapentin, also reduce hot flashes, but not to the same degree as estrogen or progesterone. One agent cannot be guaranteed to work for everyone, and there are side effects associated with any of these treatments. Nonetheless, options are available for women who wish to have therapy for their hot flashes. Supported by an independent educational grant from Susan G. Komen for the Cure. ------------------------------------------------------------------------------------------- Saturday March 1, 07:17 AM Weight a key in breast cancer risk Women have been told if they put on weight in their late teens, their chances dropped of getting breast cancer before menopause . However, after menopause women reduced the risk of breast cancer by losing weight or keeping their weight down and not doing hormone replacement therapy for longer than five years. That was the message from Dr Karin Michels from the Harvard Medical School, at a public lecture in Auckland this week. Breast Cancer Advocacy Coalition spokeswoman Libby Burgess, who was at the lecture, said for women who had had breast cancer, the message was that no dietary factors had been identified as of great relevance in the risk levels but for post menopausal women, weight loss and exercise increased the survival rate. Spending 10 minutes a day in the sun in shorts and a tee shirt and without sunscreen meant the body would absorb 10,000 units of Vitamin D. Ms Burgess, said a woman needed 4000 units of Vitamin D a day to reduce the breast cancer risk but that needed to be weighed against the possible increased risk of skin cancer from not wearing sun screen. Dr Michels, an epidemiologist at Harvard and a well-published cancer researcher, was brought to New Zealand by the Liggins Institute and the Breast Cancer Research Trust as part of her research into the cause of breast cancer in women and the high rate of breast cancer in New Zealand. Dr Michels told NZPA before her public lecture that the plastic which surrounded us in our daily lives may contribute to New Zealand's high rate of cancer, particularly breast cancer. Dr Michels said she did not eat food wrapped or stored in plastic, nor would she use a plastic shower curtain. She said she and her medical research colleagues were "really concerned" about plastics and plasticisers used in every day life in many countries. "The plastic bottles we drink from, especially these hard plastic bottles which are reusable, the Tupperware, the baby bottles where we heat up the milk and shower curtains -- all release substances that screw up our hormone system." She said heating lunch in a plastic container in a microwave released substances into the food which entered the body. "You eat these substances that screw up your hormonal system and that has been associated with an increased risk of breast cancer in animals." The substances could also be breathed in when they were released from shower curtains during a hot shower. She said studies had yet to be done on humans because humans could not be fed carcinogenic substances. "But you can feed it to rats and if you give it to rats, they develop breast cancer." Dr Michels said heating plastic caused substances, including the carcinogenic substance bisthenol A, to be released in greater quantities than eating food stored or wrapped in unheated plastic. "You are exposed to these kind of substances almost everywhere. If you wrap your food in plastic wrap it gets into the food. "It is particularly bad for babies because the baby's small, and you heat up the milk in a plastic body and all that stuff gets into the formula. "The baby gets all these chemicals and who knows what it does to the baby? We don't really know but it is something we are extremely concerned about." Bisthenol A was the substance that most concerned the medical research industry. She said the substances still came out of the plastic even when it was not heated. "It is a very scary thought." Dr Michels said the increasing use of plastic, such as plastic jars in supermarkets was not a good practice. "Good old glass is probably better." She said the potential risk from plastic had only been discovered recently but was hard to study because plastic was so widely used. In New Zealand breast cancer killed more than 600 women a year Part of her research into breast cancer was to look at the relationship between diet and the disease. She said while the research had yet to identify the risk factors in breast cancer from food, alcohol had been identified as a risk. "Alcohol consumption like a glass of wine a day already increases your risk of breast cancer by 20 percent." That risk could be countered with a daily folate or B vitamin pill. A low-fat diet and regular exercise for young girls may also lower the cancer risk factor. She said diet before puberty could also affect the risk rate for breast cancer although the research in that area was still very preliminary and more was needed. A high birth weight also increased the risk factor for breast cancer, but the risk factors from the time of conception to puberty or early adulthood had not been considered. "That is something we have totally missed out on before for many years, almost decades, that we have done epidemiologic research which is the research that identifies risk factors for breast cancer." Dr Michels said the rise in the rate of breast cancer must be attributed to lifestyle and environment because women who moved from a country with a low rate of breast cancer to a country with a high rate, adopted the cancer rate of their new country. "It must be lifestyle. It is not genetic," she said. *********************************************************************** ********************* Intervention Program Boosts Health in Breast Cancer Patients Psychological interventions for cancer patients do more than just ease emotional distress – they directly improve health, new research suggests. A study of 227 breast cancer patients found that those who participated in a psychological intervention program were rated as having better health by a research nurse a full year after the program started. One particularly important result was that patients who exercised received a higher dose of their chemotherapy drug, possibly improving their overall treatment. “Patients who participated in the program showed fewer and less severe symptoms, and functioned better than those who didn’t take part,” said Barbara Andersen, co-author of the study and professor of psychology at Ohio State University. “These were independent health evaluations by nurses who didn’t know which patients were participating in the psychological intervention, so we know the effects were real and significant.” The results were reported in recent issues of the Journal of Consulting and Clinical Psychology and Brain, Behavior, and Immunity. Participants in the study were breast cancer patients at the Ohio State University Medical Center. All had been diagnosed with Stage II or Stage III breast cancer, had received mastectomies, and underwent chemotherapy during the course of the study. Half the patients received the intervention, in which they met weekly in groups of 8 to 12 with a clinical psychologist. These sessions, which lasted four months, included training on relaxation and coping with stress, strategies to improve health behaviors, information on the value of exercise, communication skills for dealing with physicians, and other related issues. After four months of these weekly meetings, participants met monthly for another eight months. At the beginning of the study, and again at 4 and 12 months, trained research nurses evaluated the participants’ health and physical functioning using a standard 100-point scale used in cancer patients. Results showed that after 12 months, those who participated in the intervention increased their functioning score by 7 percent, compared to only 1 percent in the group that didn’t participate. Disease symptoms and signs and treatment side effects increased by 29 percent in those who didn’t participate in the intervention, but only 14 percent in those who did take part. “These changes were big enough to be clinically important,” Andersen said. “When patients have better health, they have less emotional distress, better quality of life, and are more likely to follow through on their treatment.” In the Journal of Consulting and Clinical Psychology paper, the researchers studied exactly which parts of the intervention were most helpful in improving the health and functioning of patients. Results showed that the use of relaxation techniques was most effective in controlling stress. Learning relaxation, as well as techniques to communicate with doctors, strategies for increasing physical activity and how to deal with stress all were related with fewer symptoms and signs associated with disease. In addition, participants who exercised as part of the intervention received a significantly higher dose of taxol – their chemotherapy drug – than did women who exercised less or not at all. “The actual dosage differences were substantial,” Andersen said. Those who exercised regularly received 99 percent dose intensity, compared to 88 percent for those patients who were less active. While all the women were prescribed the same relative levels of taxol, some women received less than the prescribed amount because of side effects related to taxol use, such as high fever, infections, and loss of sensation in hands and feet. Women with severe symptoms would get a reduced dose of taxol or had longer intervals between taxol treatments. “Women who exercised regularly tolerated the taxol treatment better, had less severe symptoms and received an increased dose intensity compared to others,” Andersen explained. Researchers also tested blood samples from the participants to determine if the intervention had any effect on measures of immune function. Results showed that women in the intervention did indeed show signs of improved immune function compared to those who did not participate. However, these improvements were not linked to better health. “We still don’t know the clinical relevance of the improvements in immune function,” she said. “We will continue to look at the participants to see whether these immune changes have any impact on the progression of the disease.” SOURCES: Journal of Consulting and Clinical Psychology, December 2007 Brain, Behavior and Immunity, October 2007 Ohio State University (http://www.osu.edu) *********************************************************************** ********************* Digital Mammography Superior to Film Mammography in Some Cases For some women, digital mammography may be a better screening option than film mammography, according to newly published results from the Digital Mammographic Imaging Screening Trial (DMIST). The results appear in the journal Radiology. The study found that digital mammography performed better than film mammography for pre- and perimenopausal women under age 50 with dense breasts. “We looked at a cross-section of characteristics,” said DMIST principal investigator, Etta D. Pisano, M.D., Kenan professor of radiology and biomedical engineering at the University of North Carolina School of Medicine in Chapel Hill. “This paper confirms that if you are under 50, pre- or perimenopausal, and have dense breasts, you should definitely be screened with digital rather than film.” DMIST enrolled 49,528 women at 33 centers in the U.S. and Canada. The women underwent both digital and film mammography. Breast cancer status was determined for 42,760 women. “The original DMIST results showed that digital was statistically similar to film in the overall screening population but performed better than film in pre- and perimenopausal women under 50,” Pisano said. For this paper, the researchers sought to retrospectively compare the accuracy of digital mammography versus film mammography in subgroups defined by combinations of age, menopausal status and breast density, using either biopsy results or follow-up information. They compared results in 10 different subgroups of women: pre- and perimenopausal women under age 50 with fatty breasts, pre- and perimenopausal women under age 50 with dense breasts, postmenopausal women under 50 with fatty breasts, postmenopausal women under 50 with dense breasts, pre- and perimenopausal women between the ages of 50 and 64 with fatty breasts, pre- and perimenopausal women age 50 to 64 with dense breasts, postmenopausal women age 50 to 64 with fatty breasts, postmenopausal women age 50 to 64 with dense breasts, women over age 65 with fatty breasts and women over 65 with dense breasts. The results confirmed the trial’s original findings in favor of improved diagnostic accuracy of digital mammography over film for pre- and perimenopausal women under 50 years old with dense breasts. The findings also showed a trend toward improved diagnostic accuracy of film over digital mammography for women over 65 with fatty breasts. However, this finding was not statistically significant, and further investigation is needed to determine the reason that film performed slightly better in this subgroup. For other groups evaluated, there was no significant difference. (Johns Hopkins is pleased to offer digital mammography to our patients.) SOURCES: Radiology, February 2008 Radiological Society of North America (http://www.rsna.org) *********************************************************************** ********************* DCIS Patients Overestimate Breast Cancer Risks Many women diagnosed with ductal carcinoma in situ (DCIS) have inaccurate perceptions of their breast cancer risks, according to a study published in the Journal of the National Cancer Institute. DCIS is a noninvasive precancer in which abnormal cells are found in the lining of a breast duct. Women with DCIS generally have a favorable prognosis—recurrence rates are low and only about one percent of DCIS patients die from breast cancer. Nonetheless, studies suggest that DCIS patients overestimate their risks of DCIS recurrence and developing invasive breast cancer. Ann Partridge, M.D., and colleagues at Dana-Farber Cancer Institute in Boston investigated perceived breast cancer risks among women with newly diagnosed DCIS and how these risk perceptions were associated with anxiety and depression. They surveyed nearly 500 newly diagnosed DCIS patients about their quality of life (including depression and anxiety) and their perceived risk of recurrence or invasive breast cancer. The surveys were completed at enrollment in the trial and then again at 9 and 18 months. At the time of enrollment, 10 percent of patients reported substantial anxiety, and two percent were depressed. Over time, anxiety levels decreased, and depression levels remained low. At enrollment, 54 percent of patients said they believed they were at least moderately likely to develop DCIS again within the next five years and 68 percent believed it was at least moderately likely to happen again at some point in their lifetime. Also, 28 percent of the women believed that it was at least moderately likely that DCIS would spread to other parts of their body. After 18 months, these perceptions had not changed substantially. Higher levels of anxiety were associated with an overestimation of future risks. “Although women with DCIS appear to experience a reasonably favorable overall quality of life, some DCIS survivors may suffer from increased distress and poor mental health that may be related to inaccurate, increased perceptions of breast cancer risks. Clinicians who are caring for the increasing number of women who are diagnosed with DCIS should be aware of these inaccurate perceptions and attempt to minimize them,” the authors write. In an accompanying editorial, H. Gilbert Welch, M.D., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and colleagues discuss the uncertainty surrounding a diagnosis of DCIS and the pitfalls of overdiagnosis and overtreatment. Since DCIS does not always progress to invasive cancer, it may be reasonable to promote active surveillance instead of performing surgery on every woman with DCIS, the editorialists note. “Active surveillance could help women whose DCIS does not progress avoid treatment and allow those whose DCIS does progress to invasive cancer be diagnosed and treated when the prognosis is still extremely favorable,” they write. But they acknowledge that active surveillance can not alleviate the effects of uncertainty and anxiety caused by the diagnosis of DCIS. To avoid these, they write, doctors should “question the value of making the diagnosis in the first place.” The editorialists suggest clinical trials be conducted to test a strategy of biopsying only those breast tumors that are large enough to be palpated (e.g., > 1 cm). SOURCE: Journal of the National Cancer Institute, online edition, February 12, 2008 *********************************************************************** ********************* BRCA1 Mutation Linked to Breast Cancer Stem Cells A new study may explain why women with a mutation in the BRCA1 gene face up to an 85 percent lifetime risk of breast cancer. Researchers from the University of Michigan Comprehensive Cancer Center found that BRCA1 plays a role in regulating breast stem cells, the small number of cells that might develop into cancers. The study, in mice and in human breast cancer cells, found that BRCA1 is involved in the stem cells differentiating into other breast tissue cells. When BRCA1 is missing, the stem cells accumulate unregulated and develop into cancer. “Our data suggest that an important reason women with BRCA1 mutations get breast cancer is that BRCA1 is directly involved in the regulation of normal breast stem cells. In these women, loss of BRCA1 function results in the proliferation of breast stem cells. Since we believe that breast cancer may originate in these cells, this explains why these women have such a high incidence of breast cancer,” said senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center. The study, published in the Proceedings of the National Academy of Sciences, provides strong support for the hypothesis that a small number of cells, called cancer stem cells, are responsible for fueling a tumor’s growth. Wicha’s lab was part of the team that first identified stem cells in human breast cancer in 2003. BRCA1 is one of two genes, that when mutated confers a high risk of breast and ovarian cancer. Previous research has shown that BRCA1 is involved in DNA repair, but it has been unclear why women with this gene mutation have such a high risk of breast cancer, up to 85 percent lifetime risk compared to 16 percent in the general population. The cancers which develop in these women are generally a more aggressive form called “triple negative type,” because they do not express hormones or proteins, including estrogen, that can be targeted with therapies. In the current study using both mice and human breast cells, researchers found that BRCA1 regulated the development of the estrogen-receptor-negative stem cells into estrogen-receptor-positive cells. When BRCA1 is missing, genetically unstable stem cells accumulate and then may develop into breast cancers. Researchers detected clusters of expanded stem cells in breast tissue isolated from women carrying BRCA1 mutations, and found that women with these expanded stem cells had a particularly high chance of developing breast cancer. “If larger studies confirm these findings, it could potentially lead to a test to identify BRCA1 carriers at particularly high risk of developing breast cancer. This might help them and their physicians make a more informed decision about preventative measures such as prophylactic mastectomy,” Wicha says. SOURCES: Proceedings of the National Academy of Sciences, online edition, January 31, 2008 University of Michigan Health System *********************************************************************** ********************* Study Finds Patients with Complex Fibroadenomas Can Avoid Surgery Complex fibroadenomas have a low incidence of malignancy, so women with this condition can be more conservatively treated and avoid surgical biopsy, according to a new study by a team of researchers from the Hadassah-Hebrew University Medical Center in Jerusalem. A fibroadenoma is a benign growth of the breast that is common in young women. They are not usually associated with breast cancer, and are often diagnosed with simple ultrasound-guided, non-surgical biopsy. Complex fibroadenomas are a subtype of fibroadenomas. They are also benign, but they have calcifications and small cysts that make their pathology more complex than simple fibroadenomas, prompting many doctors to recommend surgical removal to ensure that the fibroadenoma is not malignant. “There is a lack of information or guidelines in the medical literature about the management of complex fibroadenomas, causing a dilemma for doctors with patients who have these lesions. Because the management of these patients is not clear, there is a tendency to excise them on surgery following a needle biopsy,” said Miri Sklair-Levy, MD, lead author of the study. For the study, which was published in the American Journal of Roentgenology, the researchers evaluated the clinical and imaging presentations of biopsy-proven complex fibroadenomas in 63 patients, compared pathologies and sizes of the lesions, and then followed up after two years. They found that only one out of the 63 patients with complex fibroadenomas had a malignancy, and that the patient with a malignancy had already shown previously. “The findings from our study showed that complex fibroadenomas can be treated similar to simple fibroadenomas, meaning follow-up without the need to excise the lesions surgically. The exception to this practice would be if some atypical high-risk lesions are found, as in the case with the one patient in our study. In those situations, the complex fibroadenomas should be surgically excised to rule out malignancy,” said Sklair-Levy. SOURCES: American Roentgen Ray Society American Journal of Roentgenology, January 2008 *********************************************************************** ********************* Physician Characteristics are Associated with Quality of Cancer Care Whether a woman receives radiation after breast cancer surgery may be associated with certain characteristics of her surgeon, including sex and medical training, according to a study published in the Journal of the National Cancer Institute. Many breast cancer patients do not receive radiation after undergoing breast conservation surgery, despite the fact that this treatment is considered a standard of quality cancer care and has been shown to reduce breast cancer recurrence. Previous studies have shown that certain patient characteristics, such as a patient’s race and distance from a radiation therapy facility, are associated with receiving post-surgical radiation. But it has been unclear whether physician characteristics also play a role in the quality of breast cancer care. Dawn Hershman, M.D., of Herbert Irving Comprehensive Cancer Center at Columbia University in New York and colleagues investigated whether surgeon characteristics were associated with a patient receiving radiation after breast cancer surgery. They identified and analyzed data on nearly 30,000 women aged 65 and older with breast cancer who were diagnosed between 1991 and 2002 and who received breast-conserving surgery. They also collected information on the 4,453 surgeons who operated on these women—including their sex, year of graduation, medical school location, patient volume, and type of medical degree. About 75 percent of the women received radiation after surgery. Each year from 1991 to 2002, the proportion of women receiving radiation increased. Nonetheless, older women, black women, unmarried women, and those living outside urban areas were less likely to receive radiation. After adjusting for patient and tumor characteristics, the researchers found that women who received radiation were more likely to have a surgeon who was female, had an M.D. degree (compared to a D.O. degree), or was trained in the United States. “Our study is one of the first to demonstrate associations between certain surgeon characteristics and quality of breast cancer care… If confirmed, more research is needed on whether they reflect surgeon behavior, patient response, or physician-patient interactions,” the authors write. SOURCE: Journal of the National Cancer Institute, online edition, January 29, 2008 *********************************************************************** ********************* Moving Beyond Tamoxifen: The Future of Selective Hormone Receptor Modulators How did a failed contraceptive become the first targeted therapy for the treatment of breast cancer? The transformation of tamoxifen, from cast-off to lifesaver, laid the foundation for a new class of therapeutics – selective estrogen receptor modulators – that could treat or prevent a variety of human diseases, including cancer and osteoporosis, according to V. Craig Jordan, OBE, Ph.D., D.Sc., a researcher at the Fox Chase Cancer Center in Philadelphia. At the Annual Meeting of the American Association for the Advancement of Science, Jordan reported on efforts to use the lessons learned about tamoxifen to develop new hormone receptor-related drugs for both women and men. “As both a preventative and therapeutic agent, tamoxifen has been credited with saving the lives of more than a half million women over the last 30 years,” said Jordan, the Alfred G. Knudson Jr., M.D., Ph.D., Chair in Cancer Research at Fox Chase. “The process of discovery that made tamoxifen a reality has given us insights into molecular mechanisms that are currently being used to advance the creation and refinement of better drugs.” In the 1970s, Jordan’s laboratory pioneered the work that turned tamoxifen into a cancer therapy, which then jump-started a field of study into so-called designer estrogens. These drugs, called selective estrogen receptor modulators (SERMS), can have different effects on their targets, estrogen receptors, depending on where the receptor is located within a woman's body. The SERM raloxifene, for example, exhibits an anti-estrogen activity that can prevent cancer in breast tissue, but in other tissue the same drug has an estrogen-like effect that increases bone density. Currently, raloxifene, which was also developed in Jordan’s laboratory, is approved in post-menopausal women to prevent osteoporosis and treat breast cancer. “The idea that SERMs could act like an estrogen in one place and an anti-estrogen in the other has created a new dimension in drug development,” Jordan said. “Now we can look at the design of these drugs and see how they can be applied to modulate other receptor sites throughout the body.” According to Jordan, recent studies have shown light on the complex – and seemingly contradictory – mechanisms behind the activity of receptors for steroids, such as estrogen. These mechanisms include slight structural differences in the estrogen receptors themselves in different tissues, as well as co-regulatory molecules that can influence whether a SERM will turn on or shut down a particular receptor. Of the 48 or so members of the nuclear receptor family, which include the molecules inside cells that bind to estrogen and other hormones, nearly half are able to be regulated in some way. “Our knowledge of how tamoxifen and raloxifene work is now being applied to develop new drugs that are selective male hormone receptor modulators that could be used in men to improve muscle weight during sickness, but without stimulating glands like the prostate,” Jordan says. “Indeed, a whole variety of nuclear steroid hormone receptor mediated drugs are now possible because of the understanding of SERM action.” SOURCES: Annual Meeting of the American Association for the Advancement of Science, February 15, 2008, Boston, MA Fox Chase Cancer Center *********************************************************************** ********************* http://www.washingtonpost.com/wp-dyn/content/article/2008/03/10/AR2008031002935.html Study: More Women Can Cut Cancer Relapse Risk By Rob Stein Washington Post Staff Writer Tuesday, March 11, 2008; Page A12 Women who survive breast cancer are often haunted by the fear that it might come back. But new research indicates that many more women than had been thought can do something to protect themselves. Currently, women whose tumors were fueled by the hormone estrogen can take the drug tamoxifen after undergoing surgery, radiation and chemotherapy to reduce their risk of a recurrence. But tamoxifen only helps for five years. After that, it may be dangerous. Five years ago, researchers stopped a large international study early when it showed that women who had early-stage breast cancer and who took another drug, known as an aromatase inhibitor, after tamoxifen were nearly half as likely to suffer a relapse. But many questions remained, including whether it would work for women who had been diagnosed years ago. In the new research, Paul E. Goss of Massachusetts General Hospital and his colleagues looked at more than 1,500 women who had been taking a placebo in the original study but then started taking the aromatase inhibitor letrozole after the study was stopped. It had been at least a year and as many as seven years since they had stopped taking tamoxifen. Even so, compared with the risk to about 800 women who did not start taking letrozole, the risk of a recurrence was cut by 63 percent. In addition, the risk of the cancer spreading was cut 61 percent, and the chance that a new tumor would be found in the other breast dropped more than 80 percent. A second paper, also published online yesterday by the Journal of Clinical Oncology, answered another crucial question. Hyman Muss of the University of Vermont did further analysis of the original study and found that letrozole, which is sold under the brand name Femara, was effective in cutting the recurrence risk for women of all ages, including those older than 70. A third study, involving 1,598 patients, found that a different aromatase inhibitor, known as exemestane or by the brand name Aromasin, was equally effective at reducing the recurrence risk. Together, the research indicates a need for a "paradigm shift" in treating breast cancer survivors, Nancy U. Lin and Eric P. Winer of the Dana-Farber Cancer Institute wrote in an editorial accompanying the new research. *********************************************************************** ********************* Reported March 14, 2008 Mammograms in Stereo ATLANTA, Ga. (Ivanhoe Newswire) -- This year, 200,000 women in the United States will be diagnosed with breast cancer. Many more will see their doctor for an annual mammogram screening. Now, doctors at Emory University in Atlanta are testing a new diagnostic tool that cuts false positive results by almost half and could give doctors a whole new way to detect abnormalities. When Dr. Carl D'Orsi puts on these glasses, he sees mammograms in a way they've never been seen before. "It's sort of a 'Wow' factor when you first look at it," says Carl D'Orsi, M.D., a radiologist at the Emory Winship Cancer Institute in Atlanta, Ga. He's the first doctor in the United States to test a new diagnostic tool called stereoscopic digital mammography. Instead of seeing a mammogram as a flat picture, this technique fuses two images to show the breast in 3D. Polarized glasses bring the images together. "All of a sudden, you have depth. All of a sudden, you can tell what's behind something, what's in front of something, what depth something is at. It's like, 'Oh my God, this is like I'm seeing the world," Dr. D'Orsi says. In a three-year Emory University study, stereo mammography found more abnormalities and reduced false positive test results by 39-percent compared to standard mammograms. Stereo also had 79-percent accuracy, while standard mammograms had 57-percent. Dr. D'Orsi says for patients, this diagnostic tool could mean quicker diagnosis, fewer recalls for more testing, less anxiety. Marilyn Cook knows mammograms all too well … and what the waiting and worrying can be like. "If they can prevent other women from having to be recalled, you know, for a second one and a third one and ultrasound, what an amazing process is that?" Cook says. She was lucky. A mammogram led to early diagnosis and treatment of her breast cancer. Now, Cook worries about her daughters' future and hopes breakthroughs like stereo mammography can mean more success stories like her own. "Two years and a couple of months -- cancer free. Survivor. I'm a survivor," Cook says. Stereo mammography is still in the testing stages. But Dr. D'Orsi believes it holds a great deal of promise for future breast cancer screening. FOR MORE INFORMATION, PLEASE CONTACT: Winship Cancer Institute at Emory University (404) 778-1900 http://www.cancer.emory.edu *********************************************************************** ******************** Posted March 10, 2008Molecular diagnostics illuminate treatment options for breast cancer Oncotype DX leads the pack in multigene expression tests used for treatment decisions. http://www.hemonctoday.com/article.aspx?rID=26863 The field of molecular, or genomic, diagnostics is growing roughly 10% a year, about twice the rate of growth as other lab industries. While classic clinical markers can shed light on disease, they do not always provide insight into specific treatment or how to select patients who would benefit from systemic therapies or new targeted therapies. Soonmyung Paik, MD, is director of the division of pathology at the National Surgical Adjuvant Breast and Bowel Project Foundation. Photo courtesy of NSABP Foundation, Pittsburgh Particularly in breast cancer, genetic screening has illuminated that some have a genetic disposition to the disease, most notably by identifying HER-2 overexpression and subsequent susceptibility to trastuzumab (Herceptin) therapy. Genomic diagnostics goes a step further by highlighting molecular changes that can define disease behavior, both clinically and in response to therapy. Clinicians can then assess who may be more likely to have a recurrence of previously diagnosed disease. Up to 85% of women with node-negative, estrogen-receptor (ER) positive breast cancer derive significant benefit from hormonal treatment alone after surgery. Adding chemotherapy reduces the relative risk of recurrence by about 25%, according to Joseph Sparano, MD, associate chairman, Department of Oncology, Montefiore-Einstein Cancer Center, Bronx, N. Y. Added chemotherapy provides an absolute benefit of only about 1% to 5% for any given patient. Consequently, women with breast cancer are overtreated with chemotherapy. Many women would be disease free without systemic therapy or with tamoxifen treatment alone. Molecular diagnostic testing can identify women who are unlikely to reap significant benefit from adjuvant chemotherapy, thus saving many from the adverse effects of unnecessary treatment, and reducing overall health care expenditures. It’s still a relatively new field, however, and oncologists are mining it, trying to determine the best application for these tests and figure out who will — and will not — benefit from adjuvant therapy. Current biomarker tests For now, only Oncotype DX (Genomic Health, Inc.), a multigene expression test, has been included in the American Society of Clinical Oncology guidelines for use with node-negative, ER-positive breast cancer. The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Breast Cancer also include use of the Oncotype DX within the systemic adjuvant treatment decision pathway for patients with hormone receptor-positive, HER2-negative tumors that are 0.6 to 1.0 cm and moderately/poorly differentiated or with unfavorable features, or >1 cm. Steve Shak Oncotype DX is a 21-gene reverse transcription polymerase chain reaction-based assay, including 16 tumor genes and five reference genes. More than 46,000 tests have been ordered since its categorization by the Clinical Laboratory Improvement Amendments (CLIA). Performed on standard processed, formalin-fixed, paraffin-embedded tumor tissue, Oncotype DX predicts the risk of breast cancer recurrence as well as the magnitude of chemotherapy benefit. “We’ve optimized how to do a highly quantitative assay on the tumor blocks that are routinely collected, so we can learn from the past and perform clinical testing in the present and future,” said Steve Shak, MD, chief medical officer of Genomic Health. “That quadruples the rate at which we can learn what genes matter and how to use them.” Samples are sent to the Genomic Health lab in Redwood City, Calif. Oncologists receive results in 10 to 14 days. Results of the test are expressed as a computed recurrence score. A higher recurrence score is associated with a greater risk of distant recurrence and a greater magnitude of chemotherapy benefit. Generally, a lower recurrence score (<18) indicates low minimal, if any, chemotherapy benefit and treatment with hormonal therapy alone should be considered. A higher recurrence score (>30) indicates that chemotherapy should be added to hormonal therapy. For patients who score between 18 and 30, treatment options become more complicated. Chemotherapy may not be necessary for all patients in this intermediate group. Oncotype DX is expensive (about $3,500) but is usually covered by insurance. “It saves money if you end up not giving chemotherapy, and saves the patient from unnecessary toxicity as well,” said Sandra Swain, MD, medical director of the Washington Cancer Institute at Washington Hospital Center, Washington, D.C. She said surgeons as well as pathologists and oncologists should become familiar with the test. Sandra Swain “Oncotype DX is a clinical, context-specific marker. It has a clear, defined utility designed to guide treatment in ER-positive, node-negative patients treated with tamoxifen,” said Soonmyung Paik, MD, director of the division of pathology, National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation in Pittsburgh, Pa. “The success rate for the Oncotype assay is more than 98%, even when using 20-year-old samples. The assay was specifically designed to withstand degradation of the RNA in the tissue. That’s a big difference between Oncotype and other kinds of tests. They require rather pristine samples, which is not always practical.” Shak emphasized the reliability of the test, but said it is not a “recipe for treatment.” It gives a continuous value rather than a discrete range of values for the risk of recurrence. Consequently, an individual’s recurrence score and its related probability on recurrence and chemotherapy benefit are used by clinicians and patients to allow a more informed decision; the recurrence score does not provide a yes or no answer about the chance of recurrence. Still, it provides an accepted standard guideline for potential treatment options, and that allows women “to approach their disease in a much smarter way,” Shak said. Genomic Health recently added to the recurrence score individual gene scores for the estrogen and progesterone receptors. “A lot of oncologists have expressed an interest in knowing more information beyond the recurrence score. So we’ve provide additional values,” said Shak. “This is just the beginning,” he said. “We’re finally looking at what matters — the individual biology of the tumor.” TAILORx The TAILORx (Trial Assigning Individualized Options for Treatment (Rx) trial, an ongoing clinical trial incorporating Oncotype DX, focuses on women in this middle range of scores, to help determine the utility of chemotherapy in patients for whom the molecular test reveals uncertain clinical benefit. Patients in this range are randomized to receive either chemotherapy plus hormonal therapy, which they would have received anyway regardless of need, or hormonal therapy alone. The trial opened in April 2006 and will continue until 2010, with results expected by 2014. More than 10,000 patients from 900 clinical sites in the United States and Canada are expected to enroll. Trial researchers adjusted the recurrence scores (10 or less: hormonal therapy alone; 11-25: randomized to either chemotherapy plus hormonal therapy or hormonal therapy alone; 26 or higher: chemotherapy plus hormonal therapy) to minimize undertreatment in the high-risk group and the randomized group. Results from the NSABP B-20 trial, which previously validated the use of Oncotype DX, suggested that chemotherapy does not significantly reduce the risk of recurrence in this mid- range group. By attempting to more clearly delineate women in this midrange group who would benefit from added chemotherapy, the TAILORx trial will minimize overtreatment of those who would not. “The trial integrates the test into the clinical decision-making process,” said Sparano, who oversees the trial. “Oncotype DX provides prognostic information that’s more reliable than clinical information,” to help clinicians assess the risk of recurrence. There are few pitfalls associated with using readily available, banked tumor tissue. The age of the preserved tissue may affect the amount of RNA that can be extracted, Sparano said, but clinics can adjust for this variability. “At the end, if other tests are developed — because we banked tumor specimens and RNA, plasma, serum and germline DNA — we can evaluate other tests without having to repeat the entire study over again. That’s a key, co-primary objective of the study,” Sparano said. Tests using fresh tissue Mammaprint (Agendia), a 70-gene panel assay that predicts the likelihood of 10-year survival, relies on snap frozen tumor tissue, limiting its use in clinical practice. Although approved by the FDA as a prognostic tool, the test is not available for use in the United States. It is currently used in the Netherlands. Like Oncotype DX, Mammaprint targets women with node-negative, ER-positive breast cancer. In validation studies, the test was effective in predicting time to distant metastasis in women younger than 61, with stage I and stage II node-negative breast cancer. Women with a high risk for recurrence in 10 years have a 29% chance of recurrence. Conversely, the test is 90% accurate in predicting breast cancer will not recur in low-risk women. It is validated in ER-negative patients as well. The MINDACT (Microarray In Node-negative Disease May Avoid Chemotherapy) trial compares the Mammaprint molecular signature with the clinical-pathological prognostic criteria in Adjuvant! Online. The trial, with about 6,000 patients, will attempt to identify patients better suited for adjuvant chemotherapy, while demonstrating efficacy and necessity of chemotherapy in patients with a low-risk molecular prognosis and a high-risk clinical prognosis. Patients with discordant high-risk/low-risk factors are randomized to use either the Mammaprint gene signature or Adjuvant! Online clinical-pathological criteria to deter-mine treatment. Secondary objectives of the MINDACT trial include identifying and validating new gene expression signatures that may predict clinical response to specific chemo- and hormonal therapies. Swain acknowledged that Mammaprint is an important test, but “there’s no use right now for Mammaprint in routine clinical practice. We don’t know what to do with the data.” Tissue samples obtained by Mammaprint use RNARetain, an RNA preserving solution. This method has been reported to be simpler than the more commonly used formalin fixed, paraffin embedded method of tissue sampling. Tumor tissue, serum and RNA samples from MINDACT participants will be banked, providing a resource for future research. Other gene expression profiling assays include the 76-gene Rotterdam signature (Veridex) and a 41-gene signature from Germany. These use snap frozen tissue and can not be applied to routinely processed biopsy tissue, limiting their clinical application in the United States at this time. Predicting treatment outcome Microarray technology allows clinicians to search for genetic variations that may lead to developing disease. Most notably, the AmpliChip CyP450 test (Roche) can detect mutations in the CYP2D6 enzyme subtype, which metabolizes a variety of medications, including tamoxifen. These mutations may account for the lack of response in approximately 10% of women using tamoxifen. Medco Health Solutions, Franklin Lakes, N.J. and LabCorp, Burlington, N.C., are planning to launch a study of the AmpliChip CYP450 test to investigate how tamoxifen can treat some forms of breast cancer and prevent the disease in some high-risk patients. Limitations of testing While promising, molecular diagnostics raises questions about effectiveness and suitability. The tests work when used appropriately. “The pitfall of these tests is not properly utilizing them in situations where it has potential to alter treatment decisions,” said Sparano. “They really shouldn’t be ordered in patients who may not be candidates for chemotherapy, or other situations where the information gained would not influence treatment decisions.” Regulation of this category of diagnostic tools is relatively new and can be complicated. In February 2007, with its approval of Mammaprint, the FDA oversaw the validity of such tests for the first time. But the regulatory process is often slow going, even more so because of the complexity of these types of tests. And the mounting regulations may add to the cost of developing similar tests in the future. Steven Gutman Molecular diagnostics and genetic/genomic testing “is a very hard science to tame,” according to Steven Gutman, MD, MBA, director, Office of In Vitro Diagnostics at the FDA. “Clinicians underestimate the difficulty with the assay; it can be analytically challenging. They underestimate how biologically complex humans — and cancers — are.” According to Gutman, eventually predictive diagnostic testing may determine drug selection, whereby the safety and effectiveness of a particular therapy may be in danger of becoming hostage to the test. “Proper sampling is really important. For some of the more complex tests, like Mammaprint or some of the multivariate assays or multiple single assays, there are very complex issues of properly interpreting the data,” Gutman said. “The bad news is there’s a relative paucity of standardized methods and materials. The good news is that there are fairly well-established roadmaps for product evaluation. So if people want to understand the analytical or clinical performance of an assay, the map to be followed is well-described.” Some pathologists believe that simply using the estrogen receptor and related gene proliferation alone could determine treatment options, making the use of the Oncotype recurrence score unnecessary. “But that’s not the case,” according to Paik. “The other genes in the score actually contribute significantly. And when you measure estrogen receptor proliferation by immunochemistry, there is no linear relationship with clinical outcome.” Role of molecular testing in the future Paik would like to see more assays that produce linear continuous data. Gene expression is only one manifestation of molecular changes in the cell, but it does not tell the whole story. “We’ re still in the embryonic stage in this business,” said Paik. “Mutations are an issue; proteins as well. “The RNA assay is convenient. It can be applied to any gene. It’s easily adaptable and expandable. However, in a protein assay, a lot of things might have to be specifically designed for each marker, and that makes it in some sense difficult to expand easily,” he said. It is important for the practicing clinician to keep up with the technology. There is no perfect test, said Sparano, so clinicians must understand both the strengths and the limitations of new tests, as well as when and how to use them and how to interpret results. Swain sees more progress in treating diagnosed disease, rather than early screening. Treatment will one day be tailored to an individual tumor, said Swain. “In the future, we’re going to test the tumor itself, and we’ll be able to say, ‘Mrs. Jones, you have this much chance of getting a recurrence. This drug or agent would benefit you,’” said Swain. “In all fields, researchers are looking for new biomarkers and trying to link them at the very least to treatment and at the most to either diagnosis or early detection or prevention,” Gutman said. “As this field unravels it will be astounding; it will produce better preventive care; it will produce much more rapid and refined diagnostic choices, and it will provide better treatment. The potential is incredible.” – by Carey Cowles Can one test do too much? For more information: Paik S, Tang G, Shak S, et al: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726-3734. Sparano J. The TAILORx trial: individualized options for treatment. Commun Oncol. 2006;3: 494-496. Swain S. A step in the right direction. J Clin Oncol. 2006;24:3717-3718. American Society of Clinical Oncology. ASCO issues updated recommendations for breast cancer tumor marker testing. Alexandria, Va: Press Center; October 22, 2007. Available at: www.ascofoundation.org/portal/site/ASCO/menuitem. c543a013502b2a89de912310320041a0/ ?vgnextoid=12786b8240dc5110VgnVCM100000ed730ad1RCRD. Accessed October 24, 2007. European Organisation for Research and Treatment of Cancer. MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy). Available at: www.eortc. be/services/unit/mindact/documents/MINDACT_trial_outline.pdf. Accessed September 29, 2007. U.S. Food and Drug Administration. FDA news: FDA clears breast cancer specific molecular prognostic test. Washington, DC: U.S. Food and Drug Administration Newsroom; Feb. 6, 2007. Available at: www.fda.gov/bbs/topics/NEWS/2007/NEW01555.html. Accessed October 16, 2007. Butcher L. Tests could save some breast cancer patients from chemotherapy. [American College of Physicians Web site]. Available at www.acponline.org. Accessed October 16, 2007. Hitt E. New tools for predicting breast cancer recurrence: an expert interview with Dr. Soonmyung Paik. Available at www.medscape.com/viewarticle/554017. Accessed October 17, 2007. Blue Cross Blue Shield. Gene expression profiling for managing breast cancer treatment. Available at: www.empireblue.com/provider/noapplication/f2/s5/t9/pw_ad086498.pdf. Accessed October 22, 2007. Singer M. Gene chips to detect CYP variations: A new step toward customized medical therapy. Available at: www.medcompare.com/spotlight.asp?spotlightid=189. Accessed October 24, 2007. GenomeWeb Daily News. Medco and LabCorp will use AmpliChip to study PGx of tamoxifen. Available at: www.genomeweb.com/issues/news/142857-1.html. Accessed October 27, 2007. *********************************************************************** ********************* The vitamin D miracle: Is it for real? The claims have been sensational. Martin Mittelstaedt checks up on the research behind the hype MARTIN MITTELSTAEDT From Saturday's Globe and Mail March 8, 2008 at 9:32 AM EDT In the summer of 1974, brothers Frank and Cedric Garland had a heretical brainwave. The young epidemiologists were watching a presentation on death rates from cancer county by county across the United States. As they sat in a lecture hall at Johns Hopkins University in Baltimore looking at the colour-coded cancer maps, they noticed a striking pattern, with the map for colon cancer the most pronounced. Counties with high death rates were red; those with low rates were blue. Oddly, the nation was almost neatly divided in half, red in the north and blue in the south. Why, they wondered, was the risk of dying from cancer greater in bucolic Maine than in highly polluted Southern California? The two had arrived at Johns Hopkins a few days earlier, having driven their Mustang from their hometown of San Diego. Frank was about to begin graduate studies and Cedric his first job as a professor. It was July, and the trip through the sunny South gave them an idea as they studied the cancer maps: Exposure to sunshine varies dramatically depending on the latitude. What if that's what was behind the varying cancer rates? Their hypothesis, painstakingly developed and published six years later in the International Journal of Epidemiology, was that sunlight has a powerful anti-cancer effect through its role in producing vitamin D in bare skin. Those living at northern latitudes, they theorized, receive less sunlight and make less of the vitamin, which in turn increases their risk of dying from cancer. Today, with vitamin D so much in the news, it's hard to believe that it took decades for the Garlands' hypothesis to gain traction in the mainstream medical community. But the benefits of vitamin D are no longer restricted to cancer prevention: Studies have linked a shortage of the compound to such serious, chronic ailments as multiple sclerosis, diabetes, heart disease, influenza and schizophrenia. Cedric Garland, now a professor of preventive medicine at the University of California, San Diego, is so convinced of this broad link that he says, "I think vitamin D is introducing a golden age in medicine." And he's not alone. So compelling is the latest research that a number of credible medical researchers and public-health advocates, many of them in Canada, have started taking doses far above 200 to 600 international units - the daily intake recommended by Health Canada, depending on age with an upper limit of 2,000 IU. Canada's leading vitamin D researcher, the University of Toronto's Reinhold Vieth, says he has been knocking back 8,000 units a day - four times the maximum - for years. Should everyone be doing the same? Dr. Vieth says he believes that what he's doing is completely safe - after all, his intake is similar to the amount of vitamin D a sunbathing Canadian might make naturally on a summer day. And Robert Heaney, a medical researcher at Creighton University in Omaha, says his Canadian colleague is hardly alone in his super-sized approach. "All the vitamin D researchers, to a person, I've not found an exception, are convinced enough by the data to walk the walk," says Dr. Heaney, who last year helped to conduct a study, reported in the American Journal of Clinical Nutrition, that linked vitamin D supplements to an astonishing 60-per-cent decrease in cancer incidence among middle-aged and older women. Cedric Garland argues that, rather than pollutants or some other cause, insufficient levels of vitamin D are at the root of the Western world's cancer epidemic. What's more, if more people took supplements, the population of northern regions would be a lot healthier all round. "We will be preventing an extremely broad range of diseases in a single, inexpensive way with virtually no complications," he explains. "It will affect every branch of medicine and public health favourably." TOO GOOD TO BE TRUE? It seems almost inconceivable that geography could damn someone to a life-threatening illness - that the mere fact of living in a northern country such as Canada could be a health hazard. The Garland brothers' hypothesis also defies the long-held conventional view that cancer is caused mainly by bad lifestyle habits, bad genes or carcinogens. Indeed, it suggests that some types of cancer could be better described as nutritional-deficiency diseases, much like scurvy or rickets. Consequently, many experts have been skeptical, aware that much-touted nutrients in the past have often failed to live up to their initial hype. "The problem with vitamins has been that generally the evidence, for whatever reason, doesn't pan out," cautions Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. Dr. Lichtenfeld says medical authorities have been burned so often over supplements that he would like to see a "substantial amount" of additional research before he is convinced that vitamin D is the real thing. The idea that sunlight has beneficial health effects also flies in the face of advice to avoid sun exposure to reduce the risk of skin cancer. Nevertheless, the idea that vitamin D insufficiency plays a role in cancer and other chronic adult diseases continues to gain scientific credence as a plausible theory, earned new respect for the long-underappreciated vitamin. Though it first drew attention in the 1920s as a cure for rickets (bone health, not cancer, is why Health Canada even has a recommended intake), it has largely been treated like Rodney Dangerfield ever since. In our health-conscious age, it has been overshadowed by supplements such as vitamin C and beta carotene. But since the Garland brothers kicked off interest in vitamin D with their data on colon cancer, other studies have shown that more than a dozen other cancers, including the big killers, breast and prostate, as well as an array of other diseases appear sensitive to insufficiencies of the vitamin. The idea behind the research is simple: Humans evolved in a sunlight-filled environment near the equator, and still have countless biological processes exquisitely calibrated to the rich vitamin D levels we would have if we were still basking under the hot sun year-round. But by migrating to higher latitudes, where strong sunlight is not present during the fall and winter, most humans upset their vitamin D metabolism, creating susceptibilities to chronic ailments that research is now linking to insufficiencies. The question for Canadians is: If we're so short of a crucial vitamin, shouldn't we be compensating? And if we did, would vitamin D be a proverbial magic pill, capable of curing much of what ails us? Although the guidelines jointly issued by the U.S. and Canadian governments say adults need only 200 to 600 IU of vitamin D daily, depending on age, the women in Dr. Heaney's study took 1,100 IU daily, while he himself takes 1,500 IU daily. (Although the international units nomenclature makes the numbers seem large, the actual weight represented by a single IU of vitamin D is dust-like, at less than a millionth of a gram. The vitamin, by acting like a hormone in the body's cells, packs a big biological punch in minute amounts.) Radical conservatives The Canadian Cancer Society is one of the more conservative health-advocacy agencies, but last year became the first major organization in the world to embrace the idea of large-scale, population-wide vitamin D supplementation to combat cancer. It started recommending that white adults take up to 1,000 IU daily in fall and winter, and non-whites, because of their higher susceptibility to vitamin D insufficiency at northern latitudes, take that amount year- round. (Canada doesn't keep national illness statistics by race, so the degree to which non- whites are being affected by ailments linked to low vitamin D levels isn't known.) The Canadian Pediatric Society followed suit shortly after, calling for pregnant and breastfeeding women to take 2,000 IU daily, with a goal of preventing childhood diseases. The Canadian Cancer Society's decision came after years of monitoring the research. Vitamin D "kept coming up. It kept hitting the bar that reaches your attention," says Heather Logan, the society's director of cancer-control policy. "It wasn't one study and that was the end of the story. There were multiple research studies continued to be published in peer-reviewed journals." One study, in the journal Circulation, found that those with low vitamin D status had a 62-per- cent increased risk of heart failure. Another, published in Archives of Internal Medicine, found that those who take vitamin D supplements cut mortality risk by 7 per cent. A third report, by scientists at the U.S. National Cancer Institute, found that, while vitamin D didn't affect overall cancer-death risk, those with relatively high levels of it in their blood had a 72-per-cent lower risk of dying from colorectal cancer. Other studies have found that low blood levels are an excellent predictor of who goes on to develop cancer and heart disease and that people diagnosed with cancer during the vitamin D- rich summer have a better prognosis than those diagnosed during winter. Not everyone is convinced, however. Critics charge that most of the findings - such as the Garlands' cancer maps - constitute only circumstantial evidence. And when the Canadian Cancer Society asked the American Cancer Society to join them in recommending more vitamin D, it refused. "I think it's fair to say we had discussions and we agreed to disagree on that. Our position is that we really want what I call solid evidence ... that there in fact is a reduction in cancer mortality without a significant increase in risk with vitamin D supplementation," Dr. Lichtenfeld says. He wants to see drug-style clinical trials to validate the benefits and assess the risks, he says, before telling 330 million Americans to start taking supplements. Similarly, John McLaughlin, vice-president of preventive oncology for Cancer Care Ontario, says the research on vitamin D is too thin at this point to recommend taking higher doses to prevent cancer. He dismisses Dr. Heaney's study as "largely uninformative" because of its small size (about 450 women) and because the subjects also took calcium supplements, which may have affected the results. But even though Ms. Logan says the Canadian Cancer Society agrees that all the science on vitamin D may not be in yet, evidence to date strongly suggests that not acting on the implications of the research is risky. Cancers affected include such big killers as breast, prostate and colon, which will claim more than 10,000 Canadians this year. "You don't need to wait for every scientific question to be answered before you take action," Ms. Logan says. "Where there is evidence of harm, even in the face of scientific uncertainty, you should so something about it." Martin Mittelstaedt is The Globe and Mail's environment reporter. JUST D FACTS Vitamin D is measured by levels in blood. Many Canadians have 40 nanomoles/litre or less, particularly in winter. Many researchers believe levels need to be at least twice that high to reduce chronic disease risk. Vitamin D is produced when exposed skin has a photochemical reaction to ultraviolet light rays from the sun. Nearly all the vitamin D circulating in our bodies is made this way, with a typical white-skinned person in a bathing suit under a noonday summer sun in Canada producing about 10,000 international units in 15 to 20 minutes. Non-whites need about five times longer to make the same amount, because the melanin in their skin acts as a sunscreen against UVB rays. During the fall and winter, sunlight at Canadian latitudes is too weak to cause any vitamin D production. Vitamin D synthesis in skin occurs only when the UV index is three or higher, roughly the period around noon from March to October in southern parts of the country. A rule of thumb is that if your shadow is longer than you are, the sunlight is not intense enough. Some of the very few foods that contain vitamin D are: cod liver oil (1,300 IU per tablespoon); wild salmon (1,000 IU per serving); farmed salmon (250 IU); sardines (600 IU); fortified milk or orange juice (100 IU); egg yolk (25 IU); fresh shiitake mushrooms and some organ meats (traces in both). Most multivitamins contain 400 IU. Over-the-counter pills and drops contain up to 1,000 IU. Health Canada's daily intake recommendations, based primarily on a 1997 study, are: newborns to 12 months, 400 IU; age 1 to 50, 200 IU; 51 to 70, 400 IU; over 70, 600 IU; with an overall upper limit of 2,000 IU. Many vitamin D advocates say Health Canada is too conservative. The Canadian Cancer Society, for example, recommends that non-white adults take 1,000 IU daily year-round and whites take that amount in fall and winter. The Canadian Pediatric Society recommends 2,000 IU daily for pregnant and breastfeeding women. Toxicity has occurred after long-term exposure to massive amounts, ranging from 50,000 IU to 150,000 IU daily. Effects such as bone demineralization may occur with chronic daily doses exceeding 10,000 IU. No illnesses have been reported for doses under 3,800 IU daily. A U.S. study in 2007 found that overall risk of cancer in women was cut by 60 per cent when they were given 1,100 IU of vitamin D per day, plus a calcium supplement. Another study estimated the dose to cut colon-cancer risk in half: 1,000 IU daily. The amount estimated to cut breast-cancer risk in half: 4,000 IU daily. Researchers say women could stay within Health Canada guidelines and still reach 4,000 IU daily by getting 2,000 IU from diet and supplements and the rest from modest sun exposure. There is some evidence that girls can cut their future risk of breast cancer by taking high levels of vitamin D during their teens. U.S. researchers estimate that vitamin D insufficiency causes up to 60,000 premature cancer deaths a year in the country, or nearly 10 per cent of total mortality from the disease. If the same percentage applies to Canada, low vitamin D status leads to about 7,000 premature cancer deaths here annually. While there is a risk of skin cancer from overexposure to ultraviolet light, researchers say, the benefits of modest sun exposure in preventing serious, hard-to-treat cancers outweighs that risk. Furthermore, they say, skin cancer is relatively easy to treat. A 2001 Finnish study found that children given 2,000 IU daily cut their risk of getting juvenile diabetes by 80 per cent. The strong correlation between latitude and the incidence of multiple sclerosis has led researchers to suspect the trend is related to vitamin D status. In the U.S., for example, MS rates are four times higher in northern states, along the Canadian border, than in the southern parts of the country. Similarly, Australian research shows the incidence of MS increases the farther people live from the equator. The highest incidence rates in the world are found in Northern Europe and Canada. Martin Mittelstaedt GENE GENIE New insights into how the 'magic pill' works The role of vitamin D in carcinomas could explain one of the biggest mysteries about the cause of cancer: why so many people who develop the disease have no known risk factors, such as a family history of the illness. The simple answer may be that Vitamin D interacts with an unusually large number of our genes, working like a master switch to turn them on or off. Researchers believe a deficiency of the vitamin leads to a deficiency of the proteins manufactured under the direction of these genes, which then undermines key defences against seemingly unrelated diseases such as cancer, diabetes and multiple sclerosis. John White, who has been studying the antimicrobial activities of vitamin D at McGill University in Montreal, says that "virtually every cell" in the human body has receptors for vitamin D and that hundreds of different genes may be regulated by it. Vitamin D's most profound gene-influenced activity appears to be in keeping healthy the broad category of cells known as epithelium, which line the outsides of our organs and the surfaces of the structures in our body. Even though these lining tissues amount to only about 2 per cent of the weight of our bodies, they are the source of about 85 per cent of cancers, those known as carcinomas. These include cancer of the colon, prostate, pancreas and uterus, along with the most common type of breast cancer, ductal carcinoma, which develops on milk-duct lining. (The other main type of cancer, sarcomas, appear in muscles and connective tissue, and don't have a strong association with vitamin D insufficiency.) "Vitamin D is a particularly effective agent in inhibiting abnormal growth or development of malignancies in epithelial tissues," says Cedric Garland, a professor of preventive medicine at the University of California, San Diego. Although many researchers view cancer as a hopelessly complex disease with different causes for each tumour type, Dr. Garland, who has been studying vitamin D for more than three decades, believes the carcinomas have a common origin in low levels of the vitamin. By his estimate, up to 75 per cent of these cancers could be prevented if vitamin D levels were raised through supplements. "I'm convinced that cancer is largely a vitamin D deficiency disease," he says. One important function of vitamin D at the gene level that may explain its anti-cancer properties is that it helps to regulate the production of E-Cadherin, a type of biological glue that holds cells together. When this glue is in short supply, it allows epithelial cells to lose adhesion to one another, permitting some to escape from the tissue they are supposed to be embedded in. Unconstrained, these cells start to multiply at a greater rate than they otherwise would and begin forming the lesions that ultimately turn into cancers. Vitamin D plays a role in telling cells when to die, thus helping to prevent uncontrolled proliferation and curbing the growth of new blood vessels that nourish growing tumours. It may also play a role in diseases unrelated to cancer. A main biological function of epithelial cells is to be a barrier against viruses and bacteria that cause infections. Scientists speculate that when low vitamin D status weakens epithelial cells, the barrier function is compromised, exposing tissues to attack from disease-causing agents - in diabetes, for example, by weakening islet cells; in multiple sclerosis, by weakening glial cells in the nervous system; and in tuberculosis, by reducing the ability of the lung lining to repulse bacteria, according to Dr. Garland. Some medical researchers have even begun to suspect a link between vitamin D insufficiency and schizophrenia, which occurs 10 per cent more often among those born in winter and early spring, when vitamin D from sunshine is less available. Researchers in Australia are testing this hypothesis by studying the brains of rats born to pregnant mothers deprived of vitamin D - with alarming results. The vitamin-D-deprived rodent brains had more cell proliferation, enlarged ventricles and less of a protein necessary for nerve growth. "What we see is that when you take [vitamin] D out of the brain in the rodent, you can break their brain basically," says John McGrath, a professor at the Queensland Brain Institute at the University of Queensland in Brisbane. "We can change the way their brain develops." Dr. McGrath says it is too early to say whether the rodent-brain research applies to humans. But he adds that "even if only a small fraction of [the cases of ] schizophrenia could be averted by optimizing maternal nutrition, that is going to be a really important outcome." Martin Mittelstaedt =============================================================== ====================== Medical News: Breast Cancer Letrozole (Femara) Prevents Late Recurrence of Breast Cancer By John Gever, Staff Writer, MedPage Today Published: March 10, 2008 Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco Earn CME/CE credit for reading medical news BOSTON, March 10 -- The aromatase inhibitor letrozole (Femara) can prevent late recurrence of breast cancer, even when patients start on the drug long after stopping adjuvant tamoxifen, researchers here said. Rates of overall and distant recurrence were more than halved in women who began letrozole up to seven years after completing the standard five years of adjuvant tamoxifen compared with those receiving no active therapy, reported Paul E. Goss, M.D., of Massachusetts General Hospital, and colleagues online in the Journal of Clinical Oncology. Women who had surgery and completed adjuvant therapy years ago should consider starting on letrozole now, Dr. Goss said in an interview. "There are probably hundreds of thousands of breast cancer patients around the world today who are in exactly this situation," he said. He suggested oncologists should consider reaching out to their former patients to offer follow-up therapy. Action Points -------------------------------------------------------------------------------- Explain to patients who ask that the study found letrozole, started up to seven years after completing adjuvant tamoxifen therapy for breast cancer, markedly reduced rates of disease recurrence. Explain that the best results were obtained when letrozole began within three months after stopping tamoxifen. Point out that letrozole was associated with increased risk of osteoporosis and bone fracture. Dr. Goss said many patients and clinicians mistakenly believe that if breast cancer does not recur within five years of surgery, the risk of later recurrence declines. In fact, he said, the yearly risk of recurrence with hormone receptor-positive disease never declines. More than half of all breast cancer recurrences and deaths occur after five years of adjuvant tamoxifen, but longer treatment with the drug has not shown additional benefit, he and his colleagues wrote. The new findings were a follow-up to the major study of letrozole as extended adjuvant therapy in breast cancer known as MA17. It was a randomized trial in which 5,187 women who had estrogen receptor-positive breast cancer were assigned to receive placebo or letrozole beginning three months after ending the adjuvant tamoxifen regimen and continuing for a planned five years. In 2003, midway through the MA17 trial, an interim analysis showed that letrozole was clearly providing a survival benefit. The trial was unblinded and letrozole was offered to the 2,383 women in the placebo group. At that time, it had been 1.1 to 7.1 years (median 31 months) since these women ended tamoxifen treatment. That allowed Dr. Goss and colleagues to compare later outcomes in the 1,579 who switched to letrozole with those of the 804 women who chose to remain off active therapy. They hoped to determine whether late initiation of letrozole would reduce recurrence and death rates relative to no treatment. For overall disease-free survival, they found a hazard ratio of 0.37 with letrozole relative to no treatment (95% CI 0.23 to 0.61, P<0.0001). For distant disease-free survival, the hazard ratio with letrozole was 0.39 (95% CI 0.20 to 0.74, P<0.004). The hazard ratios were adjusted to reflect a significantly younger age, better performance status, and increased likelihood of positive nodes and adjuvant chemotherapy among the women who accepted open-label letrozole. It was not all good news for those taking letrozole, though, as they also experienced increased rates of bone fractures and new diagnoses of osteoporosis. Some 5.2% of women who switched to letrozole sustained fractures, versus 3.1% of the untreated patients (P=0.02). A related paper, also on patients in the MA17 trial and by the same group of researchers, was published simultaneously today in the Annals of Oncology. Those results gave long-term outcome data on how patients originally assigned to letrozole fared in comparison with those in the placebo group. On an intent-to-treat basis and after a median of 64 months of follow-up, those in the original letrozole group were significantly more likely to be alive without disease compared with those in the original placebo group, including those who subsequently switched to letrozole (adjusted HR 0.68, 95% CI 0.55 to 0.83, P=0.0001). The annual rate of contralateral breast cancer was 0.28% for those in the letrozole group, versus 0.46% for placebo patients (HR 0.61, 95% CI 0.39 to 0.97, P=0.033). These data indicate that starting letrozole within three months of completing tamoxifen is preferable to delaying it until later, Dr. Goss and colleagues said. They also suggested that these may be the best data that will ever emerge on letrozole timing, "as it is highly unlikely that the question of optimal time for initiation of letrozole extended adjuvant therapy will be studied prospectively." Letrozole is approved for extended adjuvant treatment of early-stage breast cancer in postmenopausal women who are within three months of completion of five years of tamoxifen therapy. It is also approved for standard adjuvant treatment and as therapy for active metastatic breast cancer with positive or unknown estrogen receptor status. The new analyses were supported by the Canadian Cancer Society, the National Cancer Institute of Canada, the U.S. National Cancer Institute, and Novartis Pharmaceuticals. Novartis, which markets letrozole, funded the original MA17 trial. Authors of the studies reported financial relationships with Novartis, Pfizer, Amgen, Astra Zeneca, Genentech, Genomic Health, Abraxis, and sanofi-aventis. Primary source: Journal of Clinical Oncology Source reference: Goss P, et al "Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen" Journal of Clinical Oncology 2008; DOI: 10.1200/JCO.2007.11.6798 ----------------------------------------------------------------------------------------------- ---------------------------------- Local cancer survivors inspire each other to good health By Amanda Rittenhouse, Staff Writer 03/12/2008 After participating in a University of Pennsylvania study, a group of local breast cancer survivors work out together twice a week at the YMCA's Fort Washington Wellness Center with the hope of combating lymphedema, a condition associated with breast cancer that causes swelling and can restrict movement. After the women's involvement in the University of Pennsylvania's Physical Activity and Lymphedema trial study, the YMCA and the University of Pennsylvania partnered to provide free gym memberships and 13 weeks of personal training to them. Gilda Smith, the personal trainer at the YMCA for the workout group, said every Tuesday and Thursday morning for about an hour and a half at the YMCA's Fort Washington Wellness Center the group of four to five women ranging in age from 30 to 60-plus work out together. Smith instructs the women to do simple workouts that focus on alternating between upper body strength and lower body strength. "The workouts are beneficial in helping the women prepare for everyday things that require resistance while lifting. If you exercise, your body is more prepared," Smith said. The women do warm-up stretches, cardio, use free weights and machines. Smith said the women start out exercising in baby steps and that she is able to customize an exercise routine based on a person's ability. Nancy Black, 51, is a breast cancer survivor and member of the workout group. Black, also a dietician, is a Glenside resident. She said she works with cancer patients on her job and said they don't just worry about the cancer coming back, but what they can do to affirm their health and make themselves feel good. Black said it is easier to stick with the exercise program as a group because it provides encouragement to get out and exercise. Black said she also appreciates the opportunity for camaraderie that the group allows the women to find. "Its fun to have people to exercise with. We share experiences and it's nice to have something positive come out of it," Black said. Dr. Kathryn Schmitz, an exercise physiologist with the University of Pennsylvania Center for Clinical Epidemiology and Biostatistics, said the study would be over at the end of June. About 300 women in the Philadelphia area with and without lymphedema participated in the study. Schmitz said she is hoping to find funding in order to implement the study nationally. The study compared women working out with lymphedema to women not working out with lymphedema. Though Schmitz cannot reveal the results of the study before they are released, she said overall it seems that women who have or are at risk of developing lymphedema can do strength training and not worry about the onset or worsening of the condition. "Preliminary and anecdotal evidence is good. Women are getting stronger and more fit and their lymphedema is not getting worse. If anything it is getting better," Schmitz said. Schmitz said current clinical guidelines for women who have or are at risk for lymphedema say they should not do any exercise with the affected arm. Schmitz said the study worked with eight YMCAs in the Southeastern Pennsylvania and New Jersey area and said she was pleased with the workouts the women in the study received at the centers. "The trainers have done a wonderful job. They really know how to help the women and I really hope the intervention can be continued long term. I hope the majority will continue long term and thus show that strength training improves bone density, physical function, body composition and fitness," Schmitz said. Sherry Auker, 69, of Wyndmoor, a breast cancer survivor and participant in the workout group, said the exercise strengthened her upper body and helped her with balance. She said she plans to keep up with the exercise program. "It encouraged me to not lead a sedentary life. Now at least I go there twice a week and work out. You get up in the morning and don't really want to do it but by the time you get there you are psyched. I also enjoy the socializing," she said. ----------------------------------------------------------------------------------------------- ---------------------------------- Reported March 19, 2008 Aggressive Breast Cancer: Watch Your BMI (Ivanhoe Newswire) -- A woman’s height to weight ratio -- commonly known as her BMI (body mass index) -- could reflect more than her physical appearance. A new study reveals women with a high BMI are more likely to have a worse prognosis for locally advanced and inflammatory breast cancer than those who fall into the normal or underweight range. “This is the first study to highlight the value of BMI at the time of diagnosis as a prognostic indicator in women with aggressive disease and at a high risk of recurrence,” senior author Massimo Cristofanilli, M.D. was quoted as saying. According to Dr. Christofanilli, locally advanced breast cancer (LABC) -- or cancer than has spread into surrounding tissue or lymph nodes -- account for five percent of breast cancer cases reported every ear. Inflammatory breast cancer (IBC) is rare, accounting for one percent to five percent of all breast cancer cases in the United States, but is also extremely aggressive. Study results showed 10-year survival rates of the normal or underweight women with LABC was about 57 percent and 44 percent for both overweight and obese women. The five-year survival rate of women with IBC was 45.3 percent for overweight women, 49 percent for obese women and 55.1 percent for normal or underweight women. Each of the women received similar treatments based on weight. “From a research standpoint, we really need to further look at the relationship between obesity and some endocrine factors that may explain why inflammatory breast cancer patients are more frequently obese,” Dr. Christofanilli said. “Our next step is to go back to the lab and start looking into those specific factors related to obesity in breast cancer. Insulin, estrogen levels and leptin are areas of immediate interest.” Dr. Christofanilli admits that dietary intervention would be difficult for women undergoing chemotherapy, but changes in lifestyle habits for overweight and obese patients after diagnosis are vital. SOURCE: Cancer Research, March 15, 2008 Contaminant found in heparin By RANDOLPH E. SCHMID, AP Science Writer 1 hour, 13 minutes ago WASHINGTON - U.S. health officials have identified a contaminant in batches of the blood thinner heparin associated with 19 deaths and are trying to determine how the chemical got into the drug. The lots of heparin, whose key ingredient was imported from China, were recalled Feb. 28, and Food and Drug Administration officials said Wednesday that no new deaths have been reported since that time. Dr. Janet Woodcock, head of the FDA's Center for Drug Evaluation and Research, said the contaminant is oversulfated condroitin sulfate, a chemical that does not occur naturally. Condroitin sulfate is a natural compound that occurs widely and is used as a dietary supplement but the oversulfated version has not been widely studied. "We cannot rule in or out whether this was accidentally or deliberately introduced into the product," Woodcock said, "We are investigating how it got in." The FDA has also initiated testing of imported heparin entering this country and Woodcock said the agency feels "doctors and patients now can be confident that the product on the market has been tested and is safe." Condroitin sulfate is a compound in the same family as heparin, so preliminary testing did not identify it, Woodcock said. She said more exacting tests by the government and university researchers uncovered the contaminant. Oversulfated condroitin sulfate would be less expensive to make than heparin, but FDA officials said they could not estimate the cost difference. The lots of heparin linked to hundreds of allergic reactions were marketed by Baxter International and produced in China. FDA said Chinese officials have been highly cooperative in the investigation. The investigation comes just a year after melamine was identified as a contaminate in pet food from China. Officials said an agreement signed at that time with China helped smooth the way for this investigation. FDA officials said they could not yet directly associate the oversulfated condroitin sulfate to the deaths and side effects, but it is the lone contaminant they have found in the product. A different brand of heparin has also been recalled in Germany after 80 patients there became sick, and the German manufacturer said it was narrowing down the source of contamination to another Chinese supplier On Wednesday, German regulators did not say if the contaminant they are investigating is oversulfated condroitin sulfate. Heparin is derived from pig intestines, and China is the world's leading supplier. Tiny family-run workshops near slaughterhouses send batches of raw ingredients to larger middlemen before they reach factories. ___ Associated Press business writers Matthew Perrone in Washington and Matt Moore in Germany contributed to this report. ___ On the Net: FDA: http://www.fda.gov Pap smear: Can it detect ovarian cancer? Can ovarian cancer be detected by a Pap smear? - No name / No state given Mayo Clinic breast-health specialist Sandhya Pruthi, M.D., and colleagues answer select questions from readers. Answer No. A Pap smear cannot detect ovarian cancer. A Pap smear is a procedure that collects cells from your cervix. The test effectively detects not only cervical cancer, but also changes in your cervical cells that suggest cervical cancer may develop in the future. Unfortunately, there is no standard or routine screening test for ovarian cancer. Researchers haven't yet found a screening tool that's sensitive enough to detect ovarian cancer in its early stages and specific enough to distinguish ovarian cancer from other, noncancerous conditions. Doctors don't recommend routine screening for women at average risk of ovarian cancer. For high-risk women, experts don't agree on exactly what to do for screening, when to do it or if it should be done at all. If you're at high risk of ovarian cancer, discuss the risks and benefits of screening tests with your doctor. Ongoing studies throughout the United States are specifically focused on screening for ovarian cancer. Hormone testing: Judicial inquiry probes faulty breast cancer tests Last Updated March 18, 2008 http://www.cbc.ca/news/background/cancer/inquiry.html Nonclinical Factors Affect Odds of Breast Cancer Patients Having Sentinal Node Biopsy By Karla Gale NEW YORK MAR 26, 2008 (Reuters Health) - The likelihood that a woman with early breast cancer will undergo sentinal lymph node biopsy -- as opposed to the more invasive axillary lymph node dissection -- depends in part on sociodemographic characteristics and insurance status, as well as clinical factors, according to a new study. Better outcomes are associated with sentinal lymph node biopsy (SLNB) compared with axillary lymph node dissection (ALND), including decreased lymphedema and pain. According to Dr. Amy Y. Chen, with the American Cancer Society in Atlanta, Georgia, and colleagues, little is known about factors that influence the choice of procedure. They examined these issues using the National Cancer Database, which covers facilities approved by the American College of Surgeons Commission on Cancer. Their study included 491,000 patients with T1a, T1b, T1c, and T2N0 breast cancer who received surgical treatment including lymph node sampling between 1998 and 2005. The use of SLNB increased from 26.8% in 1998 to 65.5% in 2005, Dr. Chen and her colleagues report in the Journal of the National Cancer Institute for April 2. According to multivariate analysis for the entire study period, independent risk factors for not receiving SLNB included age over 72 years, belonging to a racial/ethnic minority, and having Medicaid or no health insurance. Individuals residing in zip codes where more than 19% of residents had not graduated high school or where the median household income was less than $32,000 were more likely to receive ALND. SLNB was performed significantly less often among patients with T2 disease, those who underwent mastectomy, and those treated at community facilities. "SLNB is most appropriately done in conjunction with breast conserving surgery," Dr. Chen told Reuters Health. "Radiation is required after breast-conserving surgery, so if the physician decides that radiation is not 'do-able' after surgery, then a more comprehensive breast and lymph node surgery may be done, and thus ALND may be performed." "SLNB is technically more involved, although not necessarily more difficult," she added. "If surgeons are not trained to do SLNB or if they work in facilities that do not have the support infrastructure, ie, radiology service, then they may need to do ALND." The research team also examined trends over time and observed that, in contrast to disparities that existed in 2005, some factors, including older age, income, and health insurance status, were not associated with chances of undergoing SLNB in 1998. Disparities associated with minority status widened. According to their paper, the adjusted annual rates of SLNB in 2005 were 0.70 in whites, 0.64 in African Americans, and 0.67 in Hispanics. "Even when we controlled for low income and health insurance status, racial disparities still persisted," Dr. Chen added. "It is concerning to see that as dissemination of SLNB increased across all facility types, racial and socioeconomic status disparities increased." However, because the database does not include individual hospital characteristics, she added, they could not tell if "disproportionate groups of poorer individuals, for example, seek medical care at facilities that do not offer SLNB." These findings imply, the authors state, that "those who are more likely to receive ALND may lack resources to deal with the added burdens associated with its adverse effects." SOURCE: J Natl Cancer Inst 2008;100:462-474. ---------------------------------------------------------------------------------------- Role of MRI in breast cancer detection unclear for majority of women Available data confine the use of MRI to women at high risk for the disease. There is no dispute that magnetic resonance imaging can detect microscopic breast cancers that cannot be detected with mammography. However, whether using magnetic resonance imaging is necessary during the course of the disease, from diagnosis to treatment to follow-up, is still unknown. Eric Winer, MD, is Director of the Breast Oncology Center at Dana-Farber Cancer Institute. Photo by Karen M. Cheung According to the ACS, mammography can detect early-stage breast cancer and reduce mortality related to the disease. However, the society stated in its 2003 breast cancer screening guidelines that women at higher risk for the disease may benefit from additional screening using other modalities, such as breast ultrasound and MRI. The 2007 ACS guidelines echo the 2003 guidelines and include more evidence. Screening with MRI is still recommended for women with about a 20% to 25% greater lifetime risk for breast cancer, which includes women with a family history of the disease and women who have been treated for Hodgkin’s disease, according to data from a study conducted by Saslow et al published in CA: A Cancer Journal for Clinicians. For other groups of women, however, the role of MRI is still unclear. 0------------------------------------------------------------------- ----------------------------------------------------------- Gene discovery raises hopes of new treatment for breast cancer By Steve Connor A discovery that has "profound implications" for the diagnosis and treatment of aggressive breast cancer has been made by scientists who believe they have found a critical gene that causes a tumour to spread. The gene was known to be involved in the functioning of the immune system but a study has now shown that when it is active in a breast tumour it causes cancerous cells to break away to other parts of the body. Scientists believe the discovery raises the prospects of tests being developed to assess the risk of an aggressive form of breast cancer developing in a patient, and to find ways of treating tumours before, or even after, they have begun to spread. Breast cancer is the most common form of cancer in women, with more than 44,000 diagnosed each year. Of these, some 12,000 die every year, mostly from aggressive forms of the disease that have spread to other vital organs. The gene is responsible for a protein called SATB1 which regulates up to 1,000 other genes by binding to DNA and causing the double-stranded molecule of inheritance to open up into the two single strands that form the double helix. In studies of more than 2,000 laboratory specimens of human breast tumours, the scientists found that high levels of SATB1 are significantly linked with the deadliest forms of the cancer. They also found that high levels of SATB1 in human breast cancer cells injected into laboratory mice increases the tendency of the cancer to spread to other parts of the body – a process called metastasis. But crucially the scientists found that switching off the gene for SATB1 in the cancerous cells resulted in the appearance of fewer – or even none – of the metastatic nodules caused when a tumour begins its lethal movement away from the breast. Terumi Kohwi-Shigematsu, a scientist at the University of California, Berkeley, who led the study published in Nature, said the discovery of SATB1's role gave new understanding of how a solid cancerous tumour can splinter into metastatic tumours. "SATB1 increases the expression of genes that promote tumour growth and reduces the expression of tumour suppressors," said Dr Kohwi-Shigematsu. Among the hundreds of genes controlled by SATB1 are those involved in stimulating growth factors, or the ability of cells to stick to one another, or those sending growth signals from one cell to another – all features known to be implicated in tumour growth and spread. "In breast tumours, SATB1 reprogrammes the genome to change the expression of hundreds of genes, promoting tumour growth and metastasis," said Dr Kohwi-Shigematsu. "What we have found is a new model of altered gene regulation during the progression of tumours, which depends on SATB1's reprogramming of the gene expression profile. What results is an aggressive cancer phenotype [appearance] that promotes tumour growth and metastasis." Key facts * Breast cancer rates have increased by more than 50 per cent over the past 20 years, and by 12 per cent over the past decade in the United Kingdom. * The NHS breast-screening programme in England saves around 1,400 lives each year. * Women with a mother, sister or daughter diagnosed with breast cancer have an 80 per cent higher risk of being diagnosed with breast cancer themselves. * Most breast cancers are "sporadic", meaning they occur at random, but a small proportion are inherited within a family due to faults in genes such as BRCA1 and BRCA2. “This is an area of evolution,” Eric Winer, MD, director of the Breast Oncology Center at Dana-Farber Cancer Institute, told HemOnc Today. “The only clear role for MRI thus far is for screening in high-risk women and further characterizing indeterminate findings on mammography.” On mammography, benign and malignant lesions often have a similar appearance, a limitation that also applies to a clinical breast exam. An imaging method that accurately detects more cancers, but distinguishes between lesion types, would be a helpful tool for both radiologists and oncologists. “For some women, it is fairly easy to justify the use of breast MRI for screening,” Doug Yee, MD, director of the University of Minnesota Cancer Center and a member of HemOnc Today’ s Editorial Board, said in an interview. “At the same time, it can promote a fair amount of unnecessary anxiety.” Doug Yee Use of MRI as a screening tool does come with challenges. It is sensitive at detecting smaller cancers but also yields false positives, which result in the use of additional and often unnecessary procedures, as well as increased anxiety for women, Winer said. MRI findings may lead to changes in treatment course, particularly the type of surgery, according to Yee. Women may choose to have a mastectomy instead of breast conserving surgery due to microscopic findings on MRI. This change in surgery has not shown any benefit thus far. The survival benefit related to detecting these microscopic cancers earlier is also unknown. There is no uniformity among various radiology centers pertaining to MRI as with mammography. There are technical standards and certification requirements for mammography, but to date, there is no such standard for MRI, Yee said. The variability in the quality of MRI vs. mammography is due in part to the immaturity of MRI technology, according to Steven Harms, MD, a radiologist at the Breast Center of Northwest Arkansas and a clinical professor of radiology at the University of Arkansas for Medical Sciences. “The results of the tests can vary greatly depending upon what kind of technology you have and what kind of doctor you have interpreting the images,” Harms said in an interview. “It’s the same with all medicine. If you have a well-performed breast MRI with an experienced reader, then you are talking about an exceptional procedure with sensitivity close to 100%.” MRI is, however, an expensive procedure that is not yet cost effective for routine screening in all women, Harms said. “If it were inexpensive, there would be no question, and MRI would be done in all women,” he said. “We’re getting closer to that point, but it is only cost effective for high-risk women. We defined these high-risk groups of women to spend health care dollars wisely.” Conversely, mammography has missed cancers in some women, especially in women at a particularly high risk. According to Constance Lehman, MD, PhD, a professor of radiology and section head of breast imaging at the University of Washington Medical Center and the Seattle Cancer Care Alliance, high-risk women are more likely to have a cancer at any given time, compared with average-risk women. For the high-risk women, mammography is just not enough. Constance Lehman High-risk women In studies of high-risk women, as many as 45 cancers for every 1,000 women screened are detected, compared with four to five cancers for every 1,000 women at average risk, Lehman said. The high-risk group comprises women with a family history of the disease and women with BRCA1 or BRCA2 mutations. Women with these mutations have an increased risk for both breast and ovarian cancers in their lifetimes, when compared with the general population of women, according to the NCI. “High-risk women are a unique group of women,” Lehman told HemOnc Today. “They tend to develop their breast cancers at a younger age. This is important because when women are younger, their breast tissue is denser, and therefore a mammogram is more likely to miss their cancers.” About one-half of the women at high risk will have their cancers missed by mammography. One-half of those women will then have their cancers diagnosed at a later stage when they are more difficult to treat, Lehman said. According to the NCI, the average woman has about a 13% lifetime risk for developing breast cancer. Women with BRCA1 mutations have about a 65% lifetime risk, and women with BRCA2 mutations have about a 45% risk for developing breast cancer, according to data from a study conducted by Antoniou et al published in the American Journal of Human Genetics. Many experts recommend that women aged 25 to 31 years with these mutations start receiving yearly mammograms, according to data from a study conducted by Lehman et al published in Cancer in 2005. Data from several studies have indicated the utility of MRI for women with BRCA mutations. In a study of 1,909 women, Kriege et al found that MRI was more sensitive at detecting invasive breast cancer in women with BRCA mutations, compared with mammography and clinical breast exam. Kuhl et al conducted a surveillance cohort study of 529 women with suspected BRCA1 or BRCA2 mutations. They also found that MRI is more sensitive at detecting breast cancers. They said that mammography with or without ultrasound is not sufficient for early breast cancer diagnoses in high-risk women. MRI and surgical choice The standard of care for most patients is breast conservation therapy, which entails a lumpectomy and radiation therapy. According to Monica Morrow, MD, chief of breast surgery at Memorial Sloan-Kettering Cancer Center, MRI detects microscopic areas of cancer around the breast in 10% to 25% of women. The detection of these microscopic cancers has led some women to choose a mastectomy in place of a lumpectomy, Morrow said. However, the presence of these microscopic cancers is not new information. “We know these microscopic cancers are scattered around the breast because pathologists told us 25 years ago,” Morrow told HemOnc Today. “The question is whether identifying these cancers by MRI does the women any good. Are these women having unnecessary mastectomies for microscopic areas of cancer that could be successfully treated with radiation?” Harms also said that MRI does not just detect microscopic disease. According to the results of a study conducted by Harms et al published in Radiology, the average occult cancer picked up on MRI was 2.5 cm. In many instances, the MRI–detected lesion had a higher histologic grade than the lesion that was evident by conventional methods, Harms said. The effect of MRI on surgical decisions also goes both ways, according to Harms. “We have converted patients to lumpectomy when, if they had not had an MRI, they would have had a mastectomy,” he said. “Treatment is not one size fits all. We want the right treatment for each patient, and MRI helps determine what that is.” When women have breast conservation therapy after cancer detection from a physical exam, mammography or ultrasound, the likelihood of cancer recurring in the breast in the next 10 years is 5% or less, Morrow said. There is no evidence that altering treatment due to results on MRI improves that risk. In a study of 759 women with breast cancer, Solin et al found that there was no difference in the eight-year rates of local recurrence, contralateral breast cancer, distant metastasis or overall survival between women who had MRI at diagnosis and women who did not. All women had had breast conservation treatment. “We are debating whether MRI plays a role before surgery,” Yee said. “MRI may help the surgeon with planning the resection. On the other hand, women are making decisions that might not have been made without the information from an MRI. We have to be cautious about that, since such a choice may not affect their overall care.” Women with average risk MRI is beneficial for detecting recurrence in the high-risk woman. In the average-risk woman, the role of MRI is not quite so clear. There are no trials that show a survival benefit to MRI in general-risk women at the time of diagnosis, Lehman said. Survival and recurrence are not the only evidence of a benefit, though, Harms said. “On one side, you’ll hear people that say there is only a 5% recurrence rate, and we are doing just fine without MRI,” Harms said. “It is short-sighted to think the only measurement we have for the benefit of MRI is recurrence.” According to Morrow, there are no ongoing studies to determine whether MRI has a benefit in reducing the rate of local recurrence. Part of the reason for that is that the risk for local recurrence is low. To conduct such a study in the breast cancer population at large would require thousands of women, she said. “Studies in this population need to focus on a different question entirely,” Morrow said. “For example, can you use MRI to identify women who do not need radiation after a lumpectomy, because the rest of the breast is normal?” To study survival benefits of MRI, the same restrictions apply, Lehman said. It would require a trial that takes thousands of women and many years before data were available. Lehman said that looking at surrogate markers would be a good way to study survival in these women. Possible surrogate markers include the tumor size at diagnosis and whether the cancers have already spread to the lymph nodes. Contralateral breast cancer In women with breast cancer, the most common second primary cancer is found in the contralateral breast, with an incidence as high as 12%. Contralateral cancers are found in up to 10% of women who had normal mammograms on the contralateral breast at the time of diagnosis, according to data from a study conducted by Heron et al that was published in Cancer. In women with newly diagnosed breast cancer, MRI often identifies abnormalities in the contralateral breast, Winer said. Although, many of these abnormalities turn out to be benign, some women choose to have a bilateral mastectomy regardless because of fear or a desire to be done with evaluation, he said. According to study data published in The New England Journal of Medicine, among 969 women with breast cancer who had no clinical or mammographic abnormalities on the contralateral breast, MRI detected possible cancers in 135 women. Thirty of these were confirmed with biopsy, according to data from a study conducted by Lehman et al published in The New England Journal of Medicine in 2007. Where MRI fits in For high-risk women, many oncologists and radiologists believe that MRI is beneficial at detecting cancers missed by mammography and clinical exam. To date, the established role of MRI is in the following women: women with BRCA1 or BRCA2 mutations who want to consider not having mastectomies; women with cancer in the lymph nodes but no detectable cancer in the breast; and women who have equivocal findings on mammogram and dense breasts, Morrow said. These comprise less than 20% of breast cancers, she said. More data are needed before MRI can play a role in the screening and treatment of women with a general risk, Winer said. – by Emily Shafer Early stage breast cancer: Should MRI factor into conservation surgery, mastectomy or bilateral mastectomy? For more information: Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117-1130. Harms SE, Flamig DP, Hesley KL, et al. MR Imaging of the breast with rotating delivery of excitation off-resonance: clinical experience with pathologic correlations. Radiology. 1993;187: 493-501. Heron DE, Komarnicky LT, Hyslop T, et al. Bilateral breast carcinoma: risk factors and outcome for patients with synchronous and metachronous disease. Cancer. 2000;88:2739- 2750. Kriege M, Brekelmans C, Boetes C, et al. Efficacy of MRI and mammography for breast- cancer screening in women with a familial or genetic predisposition. N Engl J Med. 2004;351: 427-437. Kuhl CK, Schrading CK, Leutner CC, et al. Mammography, breast ultrasound and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol. 2005;23:8469-8476. Lehman CD, Blume JD, Weatherall P, et al. Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer. 2005;103:1898-1905. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;356:1295-1303. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89. Solin LJ, Orel SG, Hwang WT, et al. Relationship of breast magnetic resonance imaging to outcome after breast conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol. 2008;26:386-391. =============================================================== ========================== E75 vaccine reduced recurrence, mortality in HER2/neu breast cancer SAN DIEGO — A HER2 peptide vaccine reduced mortality by 50% in patients with HER2/neu-positive breast cancer, according to the results of a study presented yesterday at the 2008 Annual Meeting of the American Association for Cancer Research. “E75, if validated in phase-3 testing, may represent a new form of HER2/neu-directed immunotherapy, which could be utilized in the HER2/neu low-expressing group of breast cancer patients,” Linda C. Benavides, MD, a resident in general surgery at Brooke Army Medical Center, said at an April 13 press briefing. Benavides presented results from a phase-2 trial of about 200 women with node-positive and node-negative breast cancer. The trial was conducted in the adjuvant setting. Women were clinically disease free and treated with standard multimodality therapy. Ninety-two women underwent vaccination and researchers followed them for a median of 30 months. The mortality rate in women with over-expressing HER2 tumors was 9.1% for the control group vs. 3.4% for the vaccine group. In the low-expressers, mortality was 6.8% for the control group vs. 0% for the vaccine group. Recurrence rates also decreased with the vaccine. In the over- and low-expresser control groups, recurrence was 18.2%. In the vaccine group, recurrence was 13.8% for over- expressers and 10.7% for low-expressers. The vaccine also had an effect among patients who had recurrence. In the over-expressers with recurrence, the risk of mortality for the control group was 50% compared with 25% for the vaccine group. For low-expressers who recurred, the risk of mortality was 38% for the control group compared with 0% for the vaccine group. The vaccine was intradermal, given every three to four weeks for a total of six inoculations. The trial showed that the vaccine is safe with only minimal flu-like symptoms in <20% of women. – by Leah Lawrence The numbers here are very small, but the concept is good. If you can vaccinate against a protein, especially a mutant protein or an over-expressed protein, and you can demonstrate that the body has responded by making T lymphocytes that are now targeting HER2 expressing cells, that is a very important first step. I am being cautiously optimistic. – William N. Hait, MD, PhD Immediate Past President, AACR For more information: Benavides LC. #2545. Presented at: the 2008 Annual Meeting of the American Association of Cancer Research; April 12-16, 2008; San Diego. ----------------------------------------------------------------------------------------------- ---------------------------------- Drinking plus hormones may up breast cancer risk What breastcancer.org says about this article Research has found that both drinking alcohol and taking hormone replacement therapy (HRT) can increase breast cancer risk. The large study reviewed here combined the two by looking at how drinking alcohol while taking HRT affected breast cancer risk. The study looked at the drinking habits and HRT use of more than 5,000 Danish women for 20 years. The researchers found: Drinking alcohol while not taking HRT didn't really affect breast cancer risk. Postmenopausal women who were taking HRT AND drank 1 or 2 alcoholic drinks per day had a breast cancer risk that was 3 times higher than women who didn't drink and didn't take HRT. Postmenopausal women who were taking HRT AND had more than 2 alcoholic drinks per day had a breast cancer risk that was 5 times higher than women who didn't drink and didn't take HRT. Drinking alcohol increases estrogen levels. It's possible that the extra estrogen from drinking combined with the estrogen in HRT caused the dramatic increases in risk in this study. When researchers look at breast cancer risk factors, they usually focus on 1 factor. This research is different because it looked at how 2 risk factors might combine to have an even larger effect on risk. According to this study, there appears to be an association between regularly drinking alcohol while taking HRT and increased breast cancer risk. And this increase in risk is higher than it would be by drinking alcohol alone or taking HRT alone. More research needs to be done to better understand the link between drinking, taking HRT, and increased risk. In the meantime, here are some things to consider: Limiting your intake of alcohol to 4 or fewer drinks per week is good for your overall health and will probably lower your breast cancer risk. Taking HRT can increase your breast cancer risk, but HRT may be right for you if severe hot flashes or other menopausal symptoms are seriously affecting your quality of life. If you're taking HRT, try to do everything you can to minimize your breast cancer risk. Talk to your doctor about using estrogen-only HRT, which increases breast cancer risk less than combination HRT. Take HRT for the shortest time possible. Consider not drinking alcohol while on HRT. For more information on how to keep your breast cancer risk as low as it can be, visit the breastcancer.org Lower Your Risk section. Last Updated: 2008-03-11 13:00:59 -0400 (Reuters Health) NEW YORK (Reuters Health) - Even moderate drinking may raise the risk of breast cancer among postmenopausal women on hormone replacement therapy, new research suggests. A number of studies have linked regular drinking to a higher risk of breast cancer; it's thought that the risk reflects the effects of alcohol on women's levels of estrogen and other hormones. Similarly, hormone replacement therapy (HRT) after menopause has been shown to raise the risk of breast cancer. The new findings, reported in the International Journal of Cancer, suggest that alcohol and HRT may combine to further boost the odds of developing the disease. Among the more than 5,000 Danish women researchers followed, those who were on HRT and averaged one or two drinks per day had a three-fold higher risk of breast cancer than women who neither drank nor took hormones. Women who had more than two drinks per day had a nearly five-times higher risk of the disease. In contrast, drinking habits were not related to breast cancer risk among women who did not use HRT, according to Drs. Naja Rod Nielsen and Morten Gronbaek of the Danish National Institute of Public Health, Copenhagen. The findings, according to the researchers, raise the possibility that drinking affects postmenopausal breast cancer risk differently depending on women's hormone use. However, more studies are needed to confirm the interaction between alcohol and hormones, they write. The findings come from two decades' worth of data on 5,035 postmenopausal women who were surveyed about their drinking habits and hormone use at the beginning of the study. Over the next 20 years, 267 women developed breast cancer. Overall, regular drinking was linked to a slightly higher risk of the disease. But when the researchers considered hormone use, drinking affected breast cancer risk only among women who were on HRT at the outset. In one previous study of postmenopausal women taking oral estrogen, those who drank were found to have estrogen levels that were three times higher than those of non-drinkers, Nielsen and Gronbaek note. This may be one explanation for the higher breast cancer risk seen in this study, they write. If further research confirms the findings, they conclude, there should be an impact on both HRT use and recommendations for "sensible drinking limits" among postmenopausal women. SOURCE: International Journal of Cancer, March 2008. *this article is March but was not available until April. =============================================================== ===================================== Shorter radiotherapy works for early breast cancer What breastcancer.org says about this article The large study reviewed here found that women diagnosed with early-stage breast cancer who got radiation therapy at higher doses but less frequently (or for a shorter overall period of time) got just as many benefits as women who got a standard course of radiation therapy. Radiation therapy after breast cancer surgery is usually given as 25 treatments -- you're treated 5 times per week over 5 weeks. Half the women in this study received this standard schedule. The other half received fewer treatments per week for either 3 or 5 weeks, but each treatment used a higher dose of radiation. By the end of radiation therapy, the women who were on the non-standard schedule got the same total amount of radiation as the women who were on a standard schedule. The side effects were the same no matter which schedule a woman was on. The main advantage of the non-standard radiation therapy schedule was that the women got fewer treatments, which means they didn't have to go to the doctor's office as much. Scheduling daily trips to the radiation oncologist's office to get radiation therapy treatment can be a problem for some women. More research is needed before alternative radiation therapy schedules become widely used. If radiation therapy is part of your breast cancer treatment plan, you might want to talk to your doctor about this study. Ask whether a modified treatment schedule is something your radiation oncologist would consider for your specific medical situation. Together, you and your doctor can make the best choice for YOU. Last Updated: 2008-03-19 9:16:50 -0400 (Reuters Health) By Michael Kahn LONDON (Reuters) - A shorter radiation course at a lower overall dose appears as safe and effective as the standard treatment delivered over a longer period of time for women with early breast cancer, British researchers said on Wednesday. Their study of nearly 4,500 women with early breast cancer showed that the key was giving fewer -- but larger -- treatments during radiotherapy treatment. The researchers reported their findings in the journal Lancet Oncology. "The results suggest that a high total dose given in 25 small treatments is no better than simpler schedules using fewer exposures to a lower total dose," said John Yarnold of the Institute of Cancer Research and Royal Marsden Hospital, who led the study. The findings back up long-held beliefs among British cancer specialists who have used shorter radiotherapy courses compared with doctors in other developed countries like the United States, he added in a telephone interview. A shorter treatment schedule is good news for cancer patients who would not have to spend as much time in doctors' offices, the researchers said. "Our data suggests our treatment is at least as safe and effective as the international standard," Yarnold said. Nearly 4,500 women took part in the study in which about half received standard radiotherapy of 25 treatments -- five times per week over five weeks. The others received a lower total dose given in fewer, larger treatments in either three or five weeks. The rate of side effects were low, and no higher in women receiving the revised treatment while the shorter course appeared just as effective in attacking tumors, the researchers said. Breast cancer is the leading cause of cancer death among women worldwide, according to the American Cancer Society which estimated that about 465,000 women died from it globally in 2007. Treatment depends on the stage or severity of the disease. Surgery is performed to remove the tumor, radiotherapy is given to kill remaining cancer cells in the breast, and chemotherapy destroys cells that may have spread from the tumor site. The findings could also lead to better treatments in the future, especially if further research shows even higher doses during shorter radiotherapy courses are just as safe and effective, Yarnold added. "The longer term excitement is these findings are not likely to be the end," he said. http://www.breastcancer.org/treatment/radiation/new_research/20080319.jsp =============================================================== ==================================== Femara cuts cancer recurrence even if started late What breastcancer.org says about this article The study reviewed here found that taking the aromatase inhibitor Femara (chemical name: letrozole) after taking tamoxifen for 5 years reduced the risk of the breast cancer coming back (recurrence), compared to not taking Femara after tamoxifen. These results were significant, which means they likely happened because of the Femara and not just by chance. The risk of the cancer coming back was lowered by 63% in women who started taking Femara up to 7 years after finishing 5 years of tamoxifen. The women took Femara for 5 years. Hormonal therapy, with either tamoxifen or an aromatase inhibitor, is usually taken for 5 years after surgery (and possibly radiation and chemotherapy) to lower the risk of hormone-receptor- positive early-stage cancer coming back in post-menopausal women. But the risk of the breast cancer coming back doesn't end after these 5 years of hormonal therapy. (This 5-year schedule was created because taking tamoxifen longer than 5 years doesn't offer any additional benefits.) Tamoxifen works by blocking the effects of estrogen on breast cancer cells. Aromatase inhibitors help stop breast cancer from coming back by preventing the formation of estrogen. Because these two types of hormonal therapy medicines work differently, researchers wondered if taking aromatase inhibitors after 5 years of tamoxifen, for a total of 10 years of hormonal therapy, would offer additional risk reduction benefits. This study confirms earlier results showing that 10 years of hormonal therapy, first with tamoxifen, then with an aromatase inhibitor, continues to reduce the risk of the cancer coming back. About 5% of the women who took only tamoxifen for 5 years had the cancer come back during the 3 years after the research ended. Only 2% percent of the women who took tamoxifen for 5 years and then took Femara for 5 years (for a total of 10 years of hormonal therapy) had the cancer come back. When this study was started, tamoxifen was the hormonal therapy used to reduce the risk of hormone-receptor-positive early-stage breast cancer coming back in post-menopausal women. Since that time, aromatase inhibitors have been found to work a little better than tamoxifen to reduce the risk of recurrence. Besides Femara, there are two other aromatase inhibitors: Arimidex (chemical name: anastrozole) and Aromasin (chemical name: exemestane). This study looked at Femara, but it's likely that all of the aromatase inhibitors can reduce the risk of the cancer coming back when taken after 5 years of tamoxifen. If you're finishing 5 years of tamoxifen, talk to your doctor about the pros and cons of taking an aromatase inhibitor for another 5 years to continue to reduce your risk of the cancer coming back. Together, you and your doctor can decide on an approach that is right for YOU and your unique situation. Last Updated: 2008-03-11 10:13:44 -0400 (Reuters Health) By Julie Steenhuysen CHICAGO (Reuters) - Taking the breast cancer pill Femara can significantly reduce the chances that a woman's cancer will return, even long after she has stopped taking the estrogen blocker tamoxifen, U.S. researchers said on Monday. They said post-menopausal women who took the Novartis AG drug Femara anywhere from one to seven years after finishing a five-year regimen of tamoxifen reduced the risk the cancer would come back by 63 percent. "What our results have shown for the first time in breast cancer treatment history is that taking an anti-estrogen anywhere along that line appears to have a dramatic reduction in the risk of recurrence," said Dr. Paul Goss of Massachusetts General Hospital, whose study appears in the Journal of Clinical Oncology. The drug, known generically as letrozole, cut the risk of cancer spreading to other areas of the body by 61 percent, and cut the risk that a tumor would develop in the unaffected breast by more than 80 percent. Letrozole belongs to a new class of breast cancer drugs known as aromatase inhibitors, which block the production of estrogen that can lead to cancer. It is recommended for use in women past menopause. The most widely used estrogen-blocking drug is tamoxifen, which was shown to cut the risk of cancer recurrence by close to 50 percent. But benefits of the pill, sold by AstraZeneca under the brand Nolvadex and also sold generically, fall significantly after five years. Tamoxifen also raises the risk of death from strokes and endometrial cancer. But more than half of breast cancer recurrences and deaths occur five or more years after completing tamoxifen. CONTINUED RISK "What is important for doctors and patients to recognize unfortunately is that the risk of recurrence of this type of breast cancer does not end at five years," Goss said in a telephone interview. "The risk continues and the benefit remains substantial of starting late on therapy," Goss said. Goss' findings are based on an analysis of 1,579 women who decided to switch to letrozole from a placebo after the trial was halted. Their results were compared to about 800 women who stayed on the placebo. Almost three years after the study ended, those who began letrozole had only a 2 percent risk of tumor recurrence, compared with almost 5 percent in those choosing no treatment. Goss said the findings were limited by the fact that women made the decision about whether they would take the drug or not. Nevertheless, he said the findings are strong and likely to change how women with breast cancer are treated. "The risk that hormone-dependent breast cancer will recur continues indefinitely, and our results imply that aromatase inhibition is effective whenever initiated," said Goss, who is also a professor at Harvard Medical School. He said the study looked at the effects of letrozole only, but said the results will likely apply to all aromatase inhibitors. Pfizer Inc makes an aromatase inhibitor called exemestane, which it sells under the brand Aromasin, and AstraZeneca Plc makes anastrozole, sold under the brand Arimidex. Another study in the journal showed that taking another exemestane soon after completing tamoxifen treatment reduced the risk of recurrence by 56 percent. Breast cancer is the second-leading cause of cancer death among U.S. women after lung cancer. It kills 500,000 people globally every year. http://www.breastcancer.org/treatment/hormonal/new_research/20080311.jsp ---------------------------------------------------------------------------------------------- "Dose-dense" chemo cuts Herceptin heart risk-study What breastcancer.org says about this article The small study reviewed here found that when Herceptin (chemical name: trastuzumab) was given in combination with dose-dense chemotherapy, the risk of heart problems from Herceptin was lower than when Herceptin was given with a routine schedule of chemotherapy. Dose-dense chemotherapy means that the chemotherapy medicines are given every 2 weeks, instead of the routine schedule of every 3 weeks. Herceptin is a targeted therapy used to treat HER2-positive breast cancers. HER2-positive cancers have extra HER2 genes and make too many HER2 protein receptors (also called HER2/neu proteins). Herceptin works by blocking the HER2 protein on the cancer cell's surface. Because it's harder on the body, the researchers were concerned that dose-dense chemotherapy might actually increase the risk of heart problems from giving Herceptin at the same time. They were pleased to find that this wasn't the case. Only 1 woman out of 70 in this study (1.4%) had heart failure after getting Herceptin and dose- dense chemotherapy. When Herceptin is given with a routine schedule of chemotherapy, there is a 4% risk of heart problems. Dose-dense chemotherapy is a relatively new, more intensive way to give chemotherapy. Doctors may recommend a dose-dense schedule for some women because other research has shown that this approach can improve survival and decrease the risk of recurrence more effectively than a routine chemotherapy schedule. Dose-dense chemotherapy doesn't allow as much time for the immune system and red blood cells to recover between chemotherapy doses. Doctors sometimes use the medicines Neupogen (chemical name: filgrastim) or Neulasta (chemical name: pegfilgrastim) to strengthen the immune system, and Procrit (chemical name: epoetin alfa), Epogen (chemical name: epoetin alfa), or Aranesp (chemical name: darbepoetin alfa) to strengthen the red blood cell system during dose-dense chemotherapy. If you've been diagnosed with HER2-positive early-stage breast cancer, your doctor will probably consider treating you with both Herceptin and chemotherapy after surgery to lower the risk of the cancer coming back. This study suggests that dose-dense chemotherapy won't increase your risk of heart problems from Herceptin. Together, you and your doctor can decide on a treatment plan that's best for you and your unique medical and personal situation. Visit the breastcancer.org Targeted Therapies section to learn more about Herceptin and other targeted therapies used to treat breast cancer. Last Updated: 2008-03-07 13:53:32 -0400 (Reuters Health) LOS ANGELES (Reuters) - Combining targeted breast cancer treatment Herceptin with a more frequent chemotherapy regimen reduces the risk of heart problems related to the drug, according to researchers at New York's Memorial Sloan-Kettering Cancer Center. Previous studies have shown that when standard chemotherapy drugs are administered every two weeks -- a treatment plan called "dose-dense" -- the likelihood of survival is improved and the risk of cancer recurrence is lowered. But some oncologists have hesitated to use Genentech Inc's Herceptin in conjunction with more frequent chemotherapy for fear of heart damage, said Dr. Chau Dang, an oncologist at Sloan- Kettering and the study's lead researcher. "We are excited about this because we saw that the risk of cardiac toxicity is actually lower," she said. Herceptin, or trastuzumab, is an antibody-based drug used to treat the 25 percent to 30 percent of breast cancer patients who have tumors that generate a protein called HER-2. These tumors tend to grow faster and are more likely to recur than tumors that do not carry the protein. Unlike chemotherapy, which is toxic throughout the body, Herceptin is designed to target tumor cells and spare normal cells, but it still causes side effects, the most serious being congestive heart failure, which occurs in up to 4 percent of patients treated with the injected drug. The small Sloan-Kettering study demonstrated an even lower risk of cardiac toxicity when standard chemotherapy drugs are administered once every two weeks, instead of once every three weeks, which is the regimen under which previously-published trials evaluated Herceptin. The study of 70 patients with early-stage breast cancer found that just one patient, or 1.4 percent, experienced congestive heart failure after 28 months of follow-up. "There is no reason to forego giving a dose-dense regimen of chemotherapy... the toxicities are not worse," said Dr. Dang. The study will be published in the March 10 issue of the Journal of Clinical Oncology and was supported by grants from Genentech and Amgen Inc. Research News on Targeted Therapies "Dose-dense" chemo cuts Herceptin heart risk-study Glaxo's Tykerb goes head-to-head with Herceptin FDA approves Avastin for breast cancer Avastin survival data mixed in breast cancer Combo therapy with Tykerb fights brain metastases US panel rejects Avastin for use in breast cancer Herceptin eradicates aggressive tumors: study Herceptin gets European OK for breast cancer Herceptin combo to fight breast cancer US FDA OKs Genentech drug for early breast cancer Combo therapy slows breast cancer progression Tykerb Shows Benefit for HER2-positive, Herceptin-resistant Cancer Taxotere and Herceptin Reduces Recurrence of Early-Stage Breast Cancer Avastin Given with Taxol Slows Advanced Breast Cancer Herceptin After Chemo Reduces Recurrence Update on Treatments for HER2-Positive Cancer Herceptin Plus Chemo Continues to Improve Survival FDA Tells Doctors About Potential Heart Problems with Herceptin Herceptin After Chemotherapy Helps Reduce Recurrence Avastin Combined with Taxol Slows Advanced Breast Cancer Herceptin Plus Chemo Improves Survival -------------------------------------------------------------------------------- About breastcancer.org » Meet Our Medical Experts Dr. Ned Z. Carp was a major contributor to clinical trials of sentinel lymph node biopsy for early stage breast cancer. Meet the other Medical Experts. -------------------------------------------------------------------------------- DRMC hosts cancer survivor seminar ST. GEORGE — Dixie Regional Medical Center Cancer Services will sponsor a Cancer Survivor Skills Seminar on April 8 from noon to 1 p.m. in the Radiation Center Conference Room, located in the Cancer Center at the 400 East campus of the hospital. The seminar will discuss how cancer patients and survivors can manage lymphedema, a swelling condition that may result when lymph nodes have been removed as a part of cancer treatment. Lorraine Moe, lymphedema specialist for DRMC Rehabilitation Services, will teach the seminar. Moe will provide information on the options for managing lymphedema. She will also discuss the risk factors for cancer patients and how those factors can be reduced. Attendees are welcome to bring lunch with them. For reservations, please call 251-2222. Serotonin Syndrome Due to Drug Interactions Worst Pills Best Pills Newsletter article April, 2008 Over the past 25 years, drug companies have released so-called “serotonergic drugs” that increase the amount of serotonin — a neurotransmitter that regulates mood, sleep, body temperature and aggression — in the body. Many anti-depressants are serotonergic, but so are certain herbal supplements, painkillers and antibiotics. If a patient is given too much of these drugs or supplements, or if they are taken in combination with other serotonergic products, a side effect known as “serotonin syndrome” or “serotonin toxicity” may occur. Serotonin syndrome happens when there are excessive serotonin concentrations in the central nervous system. Because serotonin syndrome can progress rapidly and can be life-threatening in severe cases, it is important that patients and health professionals be aware of this condition and the drugs that can cause it. Is serotonin syndrome difficult to diagnose? Serotonin syndrome can be difficult to diagnose because many of the symptoms — such as agitation, fast heart rate, fever, sweating, flushing and the like — are nonspecific. The good news is that newer diagnostic techniques improve physicians’ ability to diagnose serotonin syndrome by focusing on the more important and specific symptoms, which mainly involve the nerves and muscles, according to the New England Journal of Medicine and the Medical Journal of Australia. For example, patients with serotonin syndrome often experience muscle jerks (called myoclonus) especially in the legs, and this symptom by itself may be enough to make the diagnosis. Other neuromuscular effects of serotonin syndrome include muscle rigidity, overactive reflexes and tremors. Importantly, in order for a doctor to diagnose serotonin syndrome, there must be a recent change in the patient’s drug therapy. Any of the following are possibilities: The recent addition of a serotonergic drug to a patient’s medication regimen; An increase in the dose of a serotonergic drug; The simultaneous use of two or more drugs that interact to increase the blood levels of a serotonergic drug. Not all physicians are aware of serotonin syndrome. A paper published in 1999 found that 85 percent of physicians were not aware of serotonin syndrome, although that percentage may have since increased. Is serotonin syndrome a newly discovered side effect? Actually, the scientific community has known about serotonin syndrome caused by drug interactions for about half a century. In the 1960s, physicians tried to treat depressed patients with drugs called MAO inhibitors in combination with tricyclic antidepressants such as imipramine (TOFRANIL, TOFRANIL PM). Both MAO inhibitors and tricyclic antidepressants are serotonergic drugs. The use of these products concurrently led to several deaths. Consequently, the Food and Drug Administration (FDA) specifically recommended against using these drugs in combination. Reports of serotonin syndrome have increased dramatically over the past two decades due mainly to the marked increase in the use of selective serotonin reuptake inhibitors (SSRIs), a class of drugs that acts specifically to increase serotonin levels. What drugs have been associated with serotonin syndrome? A large number of drugs have serotonergic effects (the most commonly used are listed in the accompanying table). Any combination of two or more of these drugs may increase the risk of serotonin syndrome. Note that some herbal and dietary supplements may have serotonergic effects, such as St. John’ s wort, ginseng and tryptophan (tryptophan is a building block of serotonin in the body). The serotonergic effect of these products is not as well established as the effects of other medications in the table. However, these and other herbal products should be avoided in general because there is not sufficient evidence that they are safe, effective or properly manufactured. The serotonergic effect of some of the drugs in the table may last for a long time. For example, fluoxetine (PROZAC, SERAFEM) can continue to interact with other drugs for up to five weeks after a patient stops using the drug. The MAO inhibitors mentioned in the table can last for two or more weeks after they are discontinued. Generally, it is a good idea to check with a physician or pharmacist for advice on how long to wait between stopping one drug and beginning another. How is serotonin syndrome treated? Prompt treatment is important. Serotonin syndrome often has a very rapid onset, and symptoms can occur soon after the interacting drug is added to the therapy. The most important step in managing serotonin syndrome is stopping the use of serotonergic drugs in consultation with your physician. If the drugs are not stopped, serotonin syndrome may progress to more serious forms. Mild cases of serotonin syndrome produce symptoms that are merely annoying and may not require treatment beyond stopping the drugs. Moderate cases require treatment but are not life- threatening. However, severe cases of serotonin syndrome can be fatal. They are a medical emergency and require immediate and vigorous treatment. The treatment is primarily supportive: fluids, anti- anxiety agents such as diazepam (VALIUM) and treatment for blood pressure changes. (Some of these might be required for moderate cases as well.) In severe cases, patients may have a very high fever due to the excessive muscle contractions. In these cases, it may actually be necessary to paralyze the muscles and place the patient on a ventilator in order to relieve the fever that results from the muscle contractions. Large doses of serotonin antagonists such as cyproheptadine (PERIACTIN) have been used with good results in some cases, but more information is needed to establish the effectiveness of this drug. How can the risk of serotonin syndrome be reduced? First, avoid taking serotonergic drugs that are “Do Not Use” in Worst Pills, Best Pills, some of which are associated with serotonin syndrome. Dextromethorphan (DELSYM), for example, is relatively ineffective as a cough suppressant and may cause serious toxicity if combined with certain other drugs. Second, patients taking any of the drugs listed in the accompanying table should check to make sure any other drugs they are taking do not interact to increase the risk of serotonin syndrome. Third, patients taking any of the drugs listed in the accompanying table should talk to a physician and/or pharmacist about serotonin syndrome to make sure they are aware of the problem. Fourth, patients taking serotonergic drugs should seek immediate medical help if any of the key symptoms of serotonin syndrome occur: muscle jerking, rigid muscles or tremor (especially if accompanied by less specific symptoms such as fever, sweating and agitation). Drugs with Serotonergic Effects Selective serotonin reuptake inhibitors: citalopram (CELEXA), escitalopram (LEXAPRO)*, fluoxetine (PROZAC), fluvoxamine (LUVOX), paroxetine (PAXIL), sertraline (ZOLOFT) MAO inhibitor antidepressants: phenelzine (NARDIL), tranylcypromine (PARNATE) Other antidepressants: clomipramine (ANAFRANIL), duloxetine (CYMBALTA), imipramine (TOFRANIL, TOFRANIL PM), mirtazapine (REMERON), nefazodone (SERZONE)*, trazodone (DESYREL), venlafaxine (EFFEXOR, EFFEXOR XR) Pain medications: fentanyl (SUBLIMAZE, ACTIQ, DURAGESIC), meperidine (DEMEROL), tramadol (ULTRAM)* Migraine drugs: sumatriptan (IMITREX), rizatriptan (MAXALT), naratriptan (AMERGE), zolmitriptan (ZOMIG), almotriptan (AXERT), eletriptan (RELPAX), frovatriptan (FROVA) Antibiotics: linezolid (ZYVOX) Herbal and dietary supplements: ginseng, St. John’s wort, tryptophan Miscellaneous: buspirone (BUSPAR), dextromethorphan (DELSYM)*, lithium, sibutramine (MERIDIA)*, bromocriptine (PARLODEL), levodopa and carbidopa (SINEMET) * Listed as “Do Not Use” drugs in Worst Pills, Best Pills book, newsletter or worstpills.org Ixabepilone: a new spin on an old idea by Laura Boehnke Michaud, PharmD, BCOP; Nousheen Samad, PharmD Anthracyclines and taxanes have long been described as the most active classes of chemotherapy against breast cancer. With incorporation of these agents into early stage breast cancer treatment regimens, researchers have conducted extensive investigation in pursuit of novel cytotoxic agents that have antitumor activity in anthracycline- and taxane-resistant disease. Capecitabine had been the only FDA-approved agent for the treatment of anthracycline- and taxane-resistant metastatic breast cancer. In June 2007, that changed when the FDA approved ixabepilone for the treatment of metastatic breast cancer. Laura Boehnke Michaud Ixabepilone (Ixempra, Bristol-Myers Squibb) is the principal agent in a new class of drugs called the epothilones. Epothilones work by stabilizing microtubules, arresting cell division at the G2M phase, and ultimately inducing cell death much like the taxanes. Despite having a similar mechanism of action to the taxanes, the epothilones are disparate in structure, allowing them to overcome resistance to taxanes. Epothilones bind to a unique site on beta-microtubules and are able to overcome traditional taxane-resistance mechanisms such as mutations (isoforms) in beta-microtubule and p-glycoprotein–mediated drug efflux pumps (eg, MDR-1). Clinical trials with ixabepilone Ixabepilone has been approved for use with capecitabine (Xeloda, Roche) for the treatment of metastatic or locally advanced breast cancer after failure of an anthracycline and a taxane. It is also approved for use as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline, a taxane and capecitabine. FDA approval of ixabepilone was based on a series of phase-2 clinical trials and one phase-3, randomized, open-label study. Results from phase-2 studies with ixabepilone demonstrated clinical activity against a variety of tumor types such as lung, ovarian, prostate, renal carcinoma, non-Hodgkin’s lymphoma and breast cancer. The results from the phase-2 studies with ixabepilone in breast cancer have demonstrated clinical benefit in those who have been previously treated and who have resistant disease despite standard therapies, as well as synergistic antitumor activity with capecitabine. Some researchers have investigated multiday treatment regimens (eg, daily × 3 to 5 days) with limited efficacy and exaggerated toxicity (eg, neurotoxicity, myelosuppression). Therefore, a single-dose regimen given every three weeks has become the standard dose for ixabepilone administered as a single agent or in combination with capecitabine. In one phase-2, multicenter study, researchers evaluated the efficacy and safety of ixabepilone in patients with metastatic breast cancer resistant to standard therapy. Eligible patients had tumor progression while on an anthracycline, taxane and capecitabine. Ixabepilone was given at a dose of 40 mg/m2 intravenously as a single agent through three hours on day one of a 21-day cycle (n=126). The objective response rate was 12%, and 13% of patients had stable disease for more than six months. The progression-free survival was 3.1 months and median overall survival was 8.6 months. Peripheral neuropathy was the most common nonhematologic adverse effect reported and severe (grade 3 or 4) neutropenia was reported in 54% of patients. However, only four patients experienced neutropenic fever and three patients had an infection during neutropenia. The promising results of the phase-2 trials gave way to a large, international, randomized phase- 3 trial. In this trial, ixabepilone with capecitabine was compared with capecitabine alone. Eligible patients included those with locally advanced or metastatic breast cancer who had been previously treated with or were resistant to anthracyclines and taxanes. Ixabepilone was given at a dose of 40 mg/m2 intravenously during three hours on day one of a 21-day cycle. Capecitabine was administered at either 2,000 mg/m2 per day orally on days one to 14 of a 21-day cycle in combination with ixabepilone, or 2,500 mg/m2 per day for 14 days as monotherapy (n=752). The addition of ixabepilone to capecitabine increased progression-free survival (HR=0.75; 95% CI, 0.64-0.88; stratified log-rank P=.0003) with a 25% reduction in the estimated risk for disease progression compared with monotherapy. Median progression-free survival was prolonged to 5.8 months (95% CI, 5.45-6.97) with the addition of ixabepilone from 4.2 months with capecitabine alone (95% CI, 3.81-4.50) — an increase of 40%. Toxicity profile The adverse effects of ixabepilone mirror those of the taxanes in many ways and appear to be schedule-dependent with more neurotoxicity seen with shorter infusions (eg, one hour infusions). The most common toxicities reported in clinical trials with single-agent ixabepilone administered to heavily pretreated patients were neutropenia/leucopenia, peripheral neuropathy, fatigue/asthenia, myalgias/arthralgias and alopecia. The use of myeloid growth factor support upfront should be considered in individual patients who are at high risk for complications related to neutropenia. Many patients had pre-existing neuropathy (<grade 2) in the clinical trials and were subsequently at higher risk for experiencing worsening of this toxicity. In the combination phase-3 trial mentioned above, 18% of patients receiving combination therapy had to discontinue therapy secondary to drug toxicity, vs. 7% of those receiving monotherapy. One of the sharpest differences in adverse effects between the two groups was peripheral neuropathy, which appears in 67% (grade 3 or 4; 21%) of patients receiving combination therapy compared to 16% (grade 3 or 4; 0%) of patients receiving monotherapy. Neuropathy was managed with dose reductions in most cases. Compared with capecitabine alone, patients in the combination group were more likely to experience neutropenia (89% vs. 43%), febrile neutropenia (19 patients vs. 2 patients) and neutropenia-related deaths (5 patients vs. 0 patients). All neutropenia-related deaths in the combination arm occurred in patients with liver dysfunction at baseline (grade >2 liver function tests: aspartate transaminase or alanine transaminase >2.5 × upper limit of normal or bilirubin >1.5 × upper limit of normal). Patients who experienced a neutropenic event were managed with subsequent dose reductions, due to the recommendation that myeloid growth factors be avoided during capecitabine therapy (days 1 to 14). Traditional capecitabine-related toxicities (eg, hand–foot syndrome, diarrhea, and mucositis) were not more frequent with the combination. Like the traditional taxanes, ixabepilone is extensively metabolized by the CYP450 system and therefore may be susceptible to a variety of drug interactions. Inducers of the enzymes will lead to decreased exposure to ixabepilone (eg, less antitumor activity and toxicity) and inhibitors to increased exposures (eg, more toxicity), respectively. The manufacturer recommends an empiric dose reduction for patients on strong inhibitors of CYP3A4. However, sound clinical judgment should always be used to determine the best dosing strategy for individual patients. Patients with hepatic impairment may experience increased exposure to the drug and increased toxicity, possibly necessitating a reduction in the dose. Ixabepilone use with capecitabine is contraindicated in patients with AST/ALT >2.5 times the upper limit of normal or bilirubin >1 times the upper limit of normal due to increased risk for toxicity and neutropenia-related death. The formulation of ixabepilone contains about 40% alcohol. The product also contains Cremophor EL (polyethoxylated castor oil, BASF Corp.) and should not be used in patients with an allergy to this excipient. This additive is also found in the formulation of paclitaxel (in greater amounts) and may lead to severe hypersensitivity reactions with ixabepilone as well. All patients receiving ixabepilone must be premedicated with an H1 antagonist (eg, diphenhydramine or hydroxyzine) as well as an H2 antagonist (eg, ranitidine or famotidine) prior to administration. Subsequent cycles may require steroid premedication if a hypersensitivity reaction is experienced. Stability and solubility of ixabepilone are related to solution concentration and pH. Ixabepilone must be diluted in Lactated Ringer’s Injection, USP only due to the optimal pH of 6 to 7.5. The use of non–DEHP [d-(2-ethylhexyl) phthalate] bags and tubing is also required due to potential for leaching of plasticizer into the solution secondary to the presence of Cremophor EL. These bags and tubing systems are similar to that used with paclitaxel. Lactated Ringer’s Injection is available in a non–DEHP bag from one manufacturer (B. Braun Medical Inc.). Acceptable solubility is obtained with a narrow range for the final solution concentration of 0.2 mg/mL to 0.6 mg/mL. The final solution in this concentration is stable at room temperature and room light for about six hours. Since the dose is generally administered during a three-hour period, this allows for a three-hour window for preparation. These specific dispensing requirements necessitate some preparation and planning, but are not insurmountable obstacles. What the future holds This novel class of agents provides an additional option for patients as they progress through various therapies to treat their breast cancer. Ixabepilone seems to carry a similar adverse effect profile compared with traditional taxanes, with the ability to overcome taxane resistance. This provides an effective treatment option for patients with resistant, metastatic breast cancer while allowing for familiarity with regard to adverse effect management. Although other epothilones appear to have differing toxicity profiles from ixabepilone (eg, patupilone and diarrhea), the entire class of agents may be useful in this era of drug resistance. Nousheen Samad, PharmD, is an Oncology Pharmacy Practice Resident at the University of Texas M.D. Anderson Cancer Center. Laura Boehnke Michaud, PharmD, BCOP, FASHP, is Manager, Clinical Pharmacy Services at the University of Texas M.D. Anderson Cancer Center. For more information: Fornier MN. Ixabepilone, first in a new class of antineoplastic agents: the natural epothilones and their analogues. Clin Breast Cancer. 2007;7:757-763. Ixempra [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2007. Larkin JMG, Kaye SB. Potential clinical applications of epothilones: a review of phase II studies. Ann Oncol. 2007;18:28-34. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Onc. 2007;25:3407-3414. Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Onc. 2007;25:5210-5217. Exercise could lower breast cancer recurrence risk and insulin levels in survivors Interview: The potential link between physical activity and recurrence in breast cancer survivors BMI linked to overall survival in locally advanced breast cancer Interview: The potential link between physical activity and recurrence in breast cancer survivors Editor's note: The following is an excerpt of an interview with Jennifer A. Ligibel, MD, instructor of medicine at Harvard Medical School. She and her colleagues found a potential relation between exercise and a significant decrease in insulin levels and hip circumference in breast cancer survivors. We performed this study because there is a growing amount of observational evidence that women who exercise after being diagnosed with breast cancer have a lower risk for recurrence. There was a report from another large study that came out recently that showed the same thing: Women who are physically active after having breast cancer had about a 50% lower recurrence risk compared with women who were inactive, and this has been observed now in three large studies. Nobody understands what really happens during exercise that could be influencing recurrence rates. So the point of our study was to look at what happens, hormonally, when women become physically active. Specif http://www.ncbi.nlm.nih.gov/pubmed/18411194?dopt=Abstract Related Articles, Links Implementation of a comprehensive cancer plan. A health planning experience. Expósito Hernández J, Domínguez Nogueira C, Escalera de Andrés C. Plan Integral de Oncología, Unidad de investigación, H.U. Virgen de las Nieves, Granada, Spain. Here we describe the working method used to implement an Integrated Cancer Health Plan in Andalusia (Spain) and to set out some of the lines of work for improving quality of care and health network planning. Four main initial considerations were made: (1) work must be centred on patients and respect for their autonomy; (2) cancer requires action at every healthcare level; (3) integration of expert professionals is to be encouraged; and (4) relevant information and data should be systematically used for planning. Two operative approaches were also established: structured participation and evidence-based healthcare. This methodology was used in various planning programmes, largely in relation to healthcare resources. In this article, as examples, we describe the development of two types of programmes: one for radiotherapy equipment and another for the management of lymphoedema in breast cancer patients. Analysis of results obtained against cancer is always controversial. It is necessary to review the healthcare structure used in terms of effectiveness and excellence. Comprehensive or integrated health plans are a useful model for a wide-ranging and multi-level approach to cancer. The structured and real participation of experts and an evidence- based healthcare strategy proved very useful in this public health planning experience. PMID: 18411194 [PubMed - in process] http://www.ncbi.nlm.nih.gov/pubmed/18411305?dopt=Abstract Related Articles, Links Emilin1 Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature. Danussi C, Spessotto P, Petrucco A, Wassermann B, Sabatelli P, Montesi M, Doliana R, Bressan GM, Colombatti A. Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, Aviano, Pordenone, Italy; IGM-CNR, Unit of Bologna c/o IOR, Bologna, Italy; Mouse Genetics Laboratory, Department of Histology Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy; Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy; and MATI Center of Excellence, University of Udine, Udine, Italy. Lymphatic vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have been poorly taken into consideration when studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril associated protein, is highly expressed by LECs in vitro and co-localizes with lymphatic vessels in several mouse tissues. A comparative study between wild-type and Emilin1(-/-) mice highlighted that Emilin1 deficiency in both CD1 and C57BL/6 background results in hyperplasia, enlargement and frequently irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. Emilin1-deficient mice also develop larger lymphangiomas than wild-type mice. Lymphatic vascular morphological alterations are accompanied by functional defects such as mild lymphedema, highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for an efficient function. The phenotype displayed by Emilin1(-/-) mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis. PMID: 18411305 [PubMed - as supplied by publisher] http://www.nugget.ca/ArticleDisplay.aspx?e=993821 Ontario Home News Ontario Mysterious swelling can be managed with therapy Mysterious swelling can be managed with therapy Posted By Cheryl Clock Posted 4 days ago The good news for Julia Gibson was that her cancer was long gone. The bad news was the unexplained swelling in her arm years after her radiation. The lump was gone. The cancer was gone. But five years later, the surgery and treatments she'd had were instigators of a new problem in her life. Gibson, 62, stood with her arms raised in front of a mirror. She compared arms, scrutinized her right, and noted, "I have no elbow." It looked swollen, and she'd been having trouble fitting it into the sleeve of her blouses. The Port Colborne woman was worried because the swelling was on the same side as the breast cancer she'd had in 2000. She'd had the lump removed as well as some lymph nodes under her arm, which later tested positive for cancer. After that, she had eight months of chemotherapy and five weeks of radiation. Her arm became infected, turning red and hot. Her doctor prescribed antibiotics, but the infection kept coming back. Finally, she told her oncologist, who recognized the problem right away: Lymphedema. Simply put, it's a chronic swelling in one part of the body, caused by a problem with the lymphatic system. Think of the lymph network as a sort of waste-disposal system. The network runs alongside blood vessels and its job is to remove impurities. Primary lymphedema happens at birth or any time in life, for unknown reasons that relate to a malformation of the lymphatic system. Secondary lymphedema is triggered by a trauma, surgery or treatment such as radiation. But often it happens months, even years, afterwards. There hasn't been a lot of research, so it's not understood why some people who have surgery and radiation develop lymphedema while others never do, said Anna Kennedy, executive director of the Lymphovenous Association of Ontario. Nonetheless, it begins when the lymph nodes are either damaged or removed. Lymph nodes are like traffic lights that direct the flow of lymph fluid, which contains specialized disease- fighting cells. If nodes are damaged or removed - most commonly through cancer surgery and treatments - then traffic doesn't flow as well. Advertisement It's like four lanes of a highway reduced to two. All you need is one accident (something as simple as a scratch that triggers an infection) and everything starts to back up, said Kennedy. Fluid backs up and causes swelling. Without treatment, that swelling can cause problems that range from an infection called cellulitis (red, blotchy skin with sudden fever and chills) to hardening of the skin, delayed wound healing and pain from heaviness - and, of course, psychological distress. Trouble is, few family doctors even recognize the signs, said Kennedy, herself a lymphedema patient who woke up one morning with a grossly swollen leg. It had been five years since her surgery for cervical cancer. There is no cure for lymphedema, although it can be successfully managed with a treatment called combined decongestive therapy (CDT), which includes an intensive phase to reduce swelling and a long-term maintenance phase to keep the swelling down. Gibson's treatments were reduced to once a month. And instead of a tight bandage, she wears a $500 compression sleeve custom-made in Germany. She only takes it off at night. Gibson also uses special skin cream to keep her arm soft and prevent cracking and infections. And even though the compression sleeve is hot in the summer and a reminder of the cancer she once had, she's not complaining. "You know what? I'll take it," Gibson said. "I feel blessed that I have a solution to my problem. I'm living. I'm enjoying my life." Article ID# 993821 http://www.ncbi.nlm.nih.gov/pubmed/18403655?dopt=Abstract Chest. 2008 Apr 10 [Epub ahead of print]Related Articles, Links Yellow Nail Syndrome: Analysis of 41 Consecutive Patients. Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Background Yellow nail syndrome is a rare condition defined by the presence of yellow nails associated with lymphedema and/or chronic respiratory manifestations. Several aspects of this disorder remain poorly defined. Methods We sought to clarify the clinical features and course associated with yellow nail syndrome by analyzing 41 consecutive cases evaluated at a tertiary referral medical center. Results There were 20 men and 21 women; the median age at diagnosis was 61 years (range, 18 to 82 years). None had a family history of yellow nail syndrome. All but one patient had chronic respiratory manifestations that included pleural effusions (46%), bronchiectasis (44%), chronic sinusitis (41%), and recurrent pneumonias (22%); 26 patients (63%) had lymphedema. Treatment included rotating antibiotic therapy for bronchiectasis, thoracenteses, oral vitamin E and corticosteroid therapy. Eight patients underwent surgical management of recurrent pleural effusions including pleurodesis and decortication; 2 additional patients underwent pleurodesis via tube thoracostomy. The yellow nails improved or resolved in 14 of 25 patients (56%) for whom the relevant data were available. Median survival of this cohort using the Kaplan-Meier method was 132 months, significantly lower than (p=0.01) the control population. Among those still alive (20 patients), the disease appeared stable. Conclusions In most cases yellow nail syndrome is an acquired disorder and associated respiratory manifestations are generally manageable with a regimen of medical and surgical treatments. Yellow nails improve in about one-half of patients, often without specific therapy. PMID: 18403655 [PubMed - as supplied by publisher] Cancer Foundation receives $100,000 support grant Print this page E-mail this article Share this article: Del.icio.us Facebook Digg Reddit Newsvine What’s this? Breast Cancer Foundation of the Ozarks, BCFO, has been awarded a 24-month Basic Support Grant in the amount of $100,000 from the Missouri Foundation for Health, said BCFO Executive Director Crystal Webster. The funds will be used for BCFO’s mammography program that helps cover the cost of mammography screenings for those who qualify in the Ozarks, and provide resources to purchase lymphedema garments for those in need, Webster said in a news release. The grant also provides for BCFO to staff a nurse/RN Educator to develop organizational, education and support services. “Missouri Foundation for Health is pleased to support BCFO in its efforts to provide important breast cancer education and mammograms for the many women in Missouri who can’t afford it. By focusing on prevention and early detection now, BCFO is helping these women live healthier lives and reduce their future medical costs,” said MFH president and CEO Dr. James R. Kimmey. The Missouri Foundation for Health is a philanthropic organization based in St. Louis whose vision is to improve the health of the people in the communities it serves. Breast Cancer Foundation of the Ozarks is a not-for-profit agency serving southwest Missouri. BCFO provides support networks, mentor programs, a full range of resources regarding breast cancer awareness, diagnosis and treatment, where to find related community services, and more. For more information on BCFO’s educational and support services, call 862-3838, toll-free at 866-874-1915, or visit bcfo.org. All requests are kept confidential. http://www.news-leader.com/apps/pbcs.dll/article? AID=/20080423/BREAKING01/80423025 Quality Cancer Care Must Address Emotional Needs Dr. Jimmie Holland Dr. Holland discusses the IOM report, "Cancer Care for the Whole Patient." Runtime: 1 minute 30 seconds. A diagnosis of cancer can be overwhelming. Ordinary concerns are often put on hold while important decisions are made and treatments begun -- treatments that can have a debilitating effect on an individual's mental and emotional health. What too frequently is overlooked during this chaotic time, both by patients and their doctors, is that quality cancer care must treat the cancer and address the patient's general well-being. A recent report by the Institute of Medicine proposes a new standard of care that integrates psychological and social support into routine care for people with cancer. The Mental and Emotional Side Effects of Cancer The psychological and social concerns of cancer patients include everything from an ongoing need for information about therapies and their resulting side effects to depression, stress, and the other mental and emotional conditions that can develop as a result of the traumatic upheavals associated with cancer treatment. These individuals may require assistance with daily activities that they can no longer perform independently, as well as with transportation, prosthetics, and medications to which they may not have easy access. The Institute of Medicine's (IOM) report, entitled "Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs," recommends that all cancer care providers screen every cancer patient at their initial visit for signs of distress, then connect patients in need with health care providers who can treat this distress, periodically reevaluating patients to determine if any changes in care are required. Sponsored by the National Academy of Sciences, of which the Institute of Medicine is a part, the report was based on the findings of a committee of experts, including Jimmie C. Holland, who holds the Wayne E. Chapman Chair in Psychiatric Oncology at Memorial Sloan-Kettering. "This report represents the first time that an organization which recommends health policy has recommended that the standard of care for cancer patients must include psychosocial care," Dr. Holland says. "This is important because, to date, most hospitals and clinics have equated cancer care with therapies used to treat cancer, excluding the mental and emotional needs of the patient being treated. This report provides a new level of credibility to this area since it confirms that there is strong evidence from the literature that psychosocial interventions are effective to help patients adhere to their treatments and reduce their distress." Lost in Outpatient Care This is a particular problem now that the majority of cancer treatment is delivered in an outpatient clinic. In this setting, many people are treated with short visits, during which there is little time for anything beyond the treatments being delivered. Cancer care providers are not in any regular, systematic way identifying the psychological and social needs of these patients, nor are they helping them to find and use available resources. Added to this is what Dr. Holland refers to as the "don't ask, don't tell" phenomenon, in which patients are reluctant to mention their emotional distress for fear of seeming weak, or of displeasing or bothering their doctors. Doctors, for their part, Dr. Holland says, often are busy and do not ask patients about any issues not directly related to treatment. "This report represents the first time that an organization which recommends health policy has recommended that the standard of care for cancer patients must include psychosocial care." -- Jimmie C. Holland, Wayne E. Chapman Chair in Psychiatric Oncology Seeking to address these problems, the report offers practical guidance to cancer care providers, showing them how they can design their practices to better address these needs of their patients. Distress Thermometer "For example," Dr. Holland explains, "we can provide what is known as a Distress Thermometer to patients in the waiting room." The Distress Thermometer is based on the pain management model used at some comprehensive cancer centers like Memorial Sloan- Kettering. In the model, patients are asked if they have pain and if so are asked to assess the intensity of the pain on a scale of 0 to 10. With the distress model, patients are routinely asked to rate their distress 0 to 10, either with a pencil and paper model in the waiting room or on a touch screen. If the response is 4 or higher, the oncology nurse or social worker should explore the cause of their distress and then, if necessary, refer patients to the appropriate psychosocial resource. Dr. Holland and her fellow committee members point out that many of the services and resources required by cancer patients in distress already exist, and are offered free of charge or are reimbursable through health insurance providers. "What this report hopefully will mean is that both patients and healthcare professionals will now know that psychosocial support is a standard part of routine cancer care," Dr. Holland suggests. "This will add tremendously to the overall quality of care." http://www.mskcc.org/mskcc/html/84855.cfm Probing the Genomic Basis for Cancer Agnès Viale and Marc Ladanyi collaborate with many members of Memorial Sloan-Kettering's research community on a variety of projects related to cancer genomics. Here they are pictured with a 454, a so-called next-generation DNA sequencer, which is changing the way investigators learn about tumors and their genetic defects. Imagine a day when a patient could have a biopsy taken from a tumor, have the entire genome of the tumor characterized, and then be treated with drugs and other therapies that are tailored to the exact genetic changes present in the tumor cells. The scenario is not science fiction, but a goal that investigators at Memorial Sloan-Kettering Cancer Center and other institutions have recognized as one of the most promising avenues for treating cancer. "The future of oncology is going to be in large part a drive toward more personalized medicine, which is more effective and has fewer side effects," said medical oncologist William Pao. "It would be similar to the way we treat infections today: We take cultures, identify the organism causing the infection, and figure out exactly which antibiotic to give. We can now envision something similar in cancer: obtain a tumor sample, identify the molecular lesions causing that tumor, and give specific targeted agents to kill it," said Dr. Pao, who is a member of the Human Oncology and Pathogenesis Program (HOPP). "As we learn more about the genetic abnormalities in human cancers, we will find there are many different subtypes among tumors that, using conventional pathology techniques, might look quite similar," said molecular pathologist Marc Ladanyi. "However, more detailed analysis will reveal subsets of a certain cancer that can benefit from a particular drug. Even if the subgroup doesn't immediately connect to a known drug, it may help us determine which tumors are likely to behave more aggressively and which patients are therefore candidates for more intensive conventional therapy." Dr. Ladanyi is a HOPP member, and he leads the Center's contribution toward a nationwide effort to catalog comprehensively the genetic changes involved in human cancer. William Pao's research is focused on the genetic changes present in lung cancer cells. For a few types of cancer, this concept is starting to become a reality. Several years ago, Dr. Pao and Memorial Sloan-Kettering President Harold Varmus, as members of an Memorial Sloan-Kettering team called the Lung Cancer Oncogenome Group (LCOG), helped determine molecular reasons why some lung adenocarcinomas (a subtype of non-small cell lung cancers) are either sensitive or resistant to the targeted therapies gefitinib (Iressa®) and erlotinib (Tarceva®). The team found that highly sensitive tumors harbor mutations in a gene called EGFR, whereas resistant tumors often contain mutations in a gene called KRAS. About 10 percent of patients with lung adenocarcinomas have EGFR mutations, and about one-quarter of lung adenocarcinomas have KRAS mutations. Based on these findings, testing for these mutations has become a part of routine care for lung cancer patients at Memorial Sloan- Kettering to help guide treatment decisions regarding the use of targeted therapies. The knowledge gained from studying these lung cancer drugs -- along with the success of other targeted therapies -- illustrates why this area of research is becoming so important. Currently, for most types of cancer, there is still much to be learned about their molecular characteristics, including the genetic changes that cause them to form, grow, and spread (metastasize) and that make some tumors more aggressive and resistant to therapy than others. Identifying a genetic change that leads to the formation of a certain tumor, however, does not necessarily mean there will be compounds available today to counteract the defect. But identification of these changes could spur the development of such agents. One of the strengths that has put Memorial Sloan-Kettering at the forefront of the search for genomic changes in cancer is its extensive tumor bank, directed by molecular pathologist and HOPP member William L. Gerald. As early as the 1980s, Memorial Sloan-Kettering surgeons, led by then-Department of Surgery Chair Murray F. Brennan, began saving thousands of tumor specimens collected from patients with all different types of cancer. These specimens are stored anonymously to protect patient confidentiality but are linked to clinical information about the patients, such as whether they responded to certain treatments, where the cancer metastasized (if it did), and whether the patients were ultimately cured. The tumor bank already has contributed to significant findings, including work by cancer biologist Joan Massagué pinpointing genes that mediate the metastasis of breast cancer to the lungs and bones. Another resource that gives Memorial Sloan-Kettering a distinct advantage in the field is its Genomics Core Laboratory and its DNA Sequencing Core Laboratory. The latter recently received a huge boost in sequencing capabilities through the purchase of an instrument called a 454 -- a "next generation" DNA sequencer. Both facilities are led by Agnès Viale. The genomics lab analyzes tumor cells using various microarrays (also called "chips"), which can monitor thousands of genes at the same time to look for changes in the number of copies of a gene or determine whether a gene is expressed, for example. Data from these microarrays might explain differences between tumor cells and normal cells or distinguish different subtypes of the same cancer. Using next-generation sequencing, investigators are able to sequence each individual DNA molecule separately, rather than combining the sequences of all fragments, as older sequencing machines do. "What this means," explained Dr. Viale, "is that if only 1 percent of cells in a tumor have an additional mutation that confers resistance to a drug treatment, we can find it. That small number of cells is what likely would be responsible for disease recurrence, and up until now we had no way to detect that rare additional mutation. This technology is beautiful, absolutely cutting edge." Recently the Center's tumor analysis capabilities were further enhanced by the creation of the Geoffrey Beene Translational Oncology Core Facility, under the leadership of Adriana Heguy. The facility, which is part of HOPP, extracts DNA from patient tumor samples, prepares the DNA for sequencing, and then outsources the material to high-volume sequencing facilities. It also performs mutation detection and data analysis using software designed by Memorial Sloan- Kettering's bioinformatics team and maintains a centralized database. "The goal of our core is to identify novel mutations in different cancer types, as well as to characterize the samples for known mutations that can ultimately translate to new options for patient care," Dr. Heguy said. "Our laboratory has been in operation for less than six months, and we are already collaborating with a large number of researchers across Memorial Sloan- Kettering who are utilizing our technology in diverse tumor types." The Center's research on genomic changes in lung adenocarcinoma is moving forward. A multidisciplinary team of clinicians and basic scientists, led by medical oncologist Mark G. Kris, has received a large grant from the National Institutes of Health to expand the work started by the LCOG. Members of the team are working on a variety of projects, including the development of newer targeted therapies; the search for additional genes that cause the formation of lung cancer, as well as genes that mediate the metastasis of lung cancer to the brain; and the study of genes related to disease persistence. "Disease persistence means that even in patients for whom targeted therapies like gefitinib and erlotinib induce massive tumor shrinkage, you never get rid of all the cancer," explained Dr. Pao. "So we're trying to figure out why these cells persist." Members of Memorial Sloan-Kettering's lung team also have participated in the Tumor Sequencing Project (TSP), a federally funded, multi-institutional collaboration that is seeking to map genomic changes in lung adenocarcinoma. In November 2007, the TSP team published a paper in Nature identifying more than 40 previously unknown genomic regions that are frequently altered in lung adenocarcinoma. The paper was based on a different approach than the one used by LCOG, a technique called single nucleotide polymorphism (SNP, pronounced "snip") profiling, which allows investigators to look for changes in the number of DNA copies that occur in tumors on a genome-wide level. [PubMed Abstract] Samuel Singer is working to characterize the genetic changes that occur in the most common types of soft tissue sarcoma. Another type of cancer on which the Center is focusing its genomics efforts is soft tissue sarcoma, a broad category of rare but aggressive tumors that affect tissues such as fat, muscle, and nerves. Through a joint project with the Broad Institute of Harvard and MIT, now funded by a grant from the Starr Cancer Consortium, Memorial Sloan-Kettering scientists are characterizing the genetic changes in several subtypes of soft tissue sarcoma, which together make up about three-quarters of all cases. "Most types of sarcoma are not sensitive to traditional chemotherapy, and that is why we set out to look for molecular changes that we might be able to target with new therapies," said surgical oncologist Samuel Singer. "We're analyzing patient samples to look for genes that are altered or amplified to see if they promote sarcoma formation," he elaborated. So far, the team has studied more than 200 sarcoma samples across seven subtypes for changes in the number of gene copies and changes in gene transcription. Investigators have sequenced more than 225 genes in 48 tumor samples and have identified mutations that may serve as potential therapeutic targets. They plan to expand the mutational analysis to additional genes and additional sarcoma samples. "Now we need to determine which mutations are the most significant, in terms of those that can be targeted with drugs, as well as those that can teach us more about how tumors behave," he said. In collaboration with several clinical departments at Memorial Sloan-Kettering, Dr. Gerald has begun a similar project with prostate cancer. The group is studying approximately 250 genes in 200 prostate tumor samples, and data generation is expected to be completed later this spring. Likewise, a project initiated by immunologist Alan N. Houghton seeks to characterize genomic changes that occur in melanoma cell lines. "We have the expertise and resources at Memorial Sloan-Kettering to make an important contribution to the cancer genome efforts," Dr. Ladanyi said. http://www.mskcc.org/mskcc/html/84549.cfm Researchers Identify New Genetic Marker for Breast Cancer March 3, 2008 NEW YORK, NY - An international group of investigators led by scientists at Memorial Sloan-Kettering Cancer Center (MSKCC) and the National Cancer Institute has identified a new genetic marker of risk for breast cancer. Women with this DNA variation are at a 1.4 times greater risk of developing breast cancer compared to those without the variation. The findings are to be published online on March 3, 2008 in the journal Proceedings of the National Academy of Sciences. [PubMed Abstract] "These results are exciting because they point us to new molecular pathways that may be associated with breast cancer," said the head of the research team and the study's senior author, Kenneth Offit, MD, MPH, Chief of the Clinical Genetics Service at MSKCC. The study used a methodology called genome-wide association mapping, which looks at genetic variations across the entire genome that alter the individual building blocks of DNA makeup. These alterations may occur more frequently in individuals who have certain types of disease than in carriers without such disease. In this study, a new gene locus, a specific place on a chromosome where a gene is located, was associated with breast cancer risk. That gene locus is on the long arm of chromosome 6. "These research findings are of great interest because of the method of genome- wide association used to discover this new locus as well as others in recent months," said Bert Gold, PhD, a Staff Scientist at the National Cancer Institute in Frederick, MD., and first author of the current study. While the risk associated with this genetic marker is much lower than that of BRCA genetic mutations for example, this discovery will increase the understanding of the genetic variants that contribute to breast cancer. “These results are exciting because they point us to new molecular pathways that may be associated with breast cancer.” -- Kenneth Offit, MD, MPH, study's senior author and Chief of the Clinical Genetics Service at MSKCC Researchers used samples largely from MSKCC, but also from other sites in the US, Canada, and Israel. Participants were all of Ashkenazi (Eastern European Jewish) ancestry. The study used a three-phase design centered on 249 families with multiple cases of breast cancer and no mutations of the BRCA genes. "This newly identified genetic marker will not have any immediate clinical implications or impact on current screening guidelines for familial breast cancer," said Dr. Offit. "As such, a test for these markers is not available to the general public and these tests should be performed only as part of research studies." Dr. Offit's research team is now confirming that this risk marker is observed in other populations, and is studying possible changes in two genes in the chromosome 6q region. The study was funded in part by federal funds from the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, the Breast Cancer Research Foundation, the Susan Komen Foundation, the Lymphoma Foundation, and the Niehaus, Southworth, Weissenbach Cancer Research Fund. -------------------------------------------------------------------------------- Journalists may contact the Department of Public Affairs for more information. Telephone: 212-639-3573 E-mail: publicaffairs@mskcc.org http://www.mskcc.org/mskcc/html/84255.cfm Cardiac Effects Associated with Breast Cancer Treatment Appear Lower with Dose-Dense Delivery of Conventional Chemotherapy Media Advisory March 6, 2008 NEW YORK - A new pilot study by investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) found that breast cancer patients can be treated safely with a "dose-dense" regimen of standard chemotherapy agents and the antibody trastuzumab (Herceptin®), a drug that has previously been shown to cause cardiac toxicity. While previous reports evaluating the cardiac effects of breast cancer treatments including trastuzumab and anthracyclines have shown an acceptable safety margin, the new study demonstrates an even lower risk of cardiac toxicity when standard doses of these drugs are administered more frequently over time -- a treatment plan called "dose-dense," which has previously been shown to be a more effective anti-cancer approach. The researchers used a dose-dense regimen of doxorubicin (Adriamycin®) and cyclophosphamide (Cytoxan® or Neosar®) followed by paclitaxel (Taxol®) and found that the regimen - when given every two weeks instead of three -- pairs safely with trastuzumab, a drug that is used to treat breast cancer in women whose tumors contain the protein receptor called HER2. According to the findings, only 1.4 percent (one patient) of the 70 early-stage breast cancer patients treated with this regimen experienced congestive heart failure after 28 months of follow- up. This rate of cardiac toxicity is lower than the 4 percent threshold that is generally considered acceptable, and still lower than what was found in larger, previously published trials evaluating conventionally scheduled treatment with the use of trastuzumab. The study's authors concluded that this dose-dense regimen combined with trastuzumab is a safe and effective way to treat women with early-stage HER2-positive breast cancer in the adjuvant setting and there is no need to forgo the use of this regimen because trastuzumab is also being administered. Chau Dang, MD, a medical oncologist on the Breast Cancer Medicine Service at MSKCC, led the study, and Clifford Hudis, MD, Chief of the Breast Cancer Medicine Service at MSKCC, is the paper's senior author. The study will be published in the March 10, 2008, issue of the Journal of Clinical Oncology and was supported by grants from Genentech and Amgen. [PubMed Abstract] -------------------------------------------------------------------------------- Journalists may contact the Department of Public Affairs for more information. Telephone: 212-639-3573 E-mail: publicaffairs@mskcc.org http://www.mskcc.org/mskcc/html/84357.cfm An Update on Complementary Therapies, Herbs, and Other Botanicals in Cancer Care Tuesday May 20, 2008 6:00 PM to 7:30 PM Type: Lecture Summary: Join Memorial Sloan-Kettering physicians Barrie R. Cassileth, PhD, Chief; Gary E. Deng, MD, PhD, Associate Attending Physician; and Kathleen M. Wesa, MD, Assistant Attending Physician, all of MSKCC's Integrative Medicine Service for a discussion of complementary therapies. Our speakers will give an overview of integrative oncology and also talk about acupuncture, herbs, and other botanicals used to treat cancer. Sponsor: CancerSmart Speaker(s): Barrie R. Cassileth, PhD Chief Integrative Medicine Service Gary E. Deng, MD, PhD Associate Attending Physician Integrative Medicine Service Kathleen M. Wesa, MD Assistant Attending Physician Integrative Medicine Service Location: Rockefeller Research Laboratories 430 East 67th Street (Between First & York Avenues) Phone: 212-639-3074 E-mail: cancersmart@mskcc.org Here is a Recap of a letter that I received from the Komen Advocacy Alliance: Did you know that there is a genetic test that can help people find out if their family history of breast cancer may be due to a genetic mutation? Unfortunately, if you are tested - and your results are positive - there are very few federal protections preventing insurance companies from denying you coverage due to your genetic condition. This has led many to forgo testing, denying them important information that could help them manage their health and the health of their families. ?But there is something we can do to change this! The Senate is debating a bill called the Genetic Information Nondiscrimination Act (GINA), which would make it illegal to discriminate based on genetic information. The House of Representatives overwhelmingly passed the Genetic Information Nondiscrimination Act last year. If this bill passes the Senate, we will have a great opportunity to promote personalized medicine and the use of genetic information in healthcare. This will lead to better research and development for new targeted drugs and treatments, which will save lives. Go to the Susan G Komen web site and there is a link that will take you to a letter that will be sent to your Senator. Please do this and forward it to your friends and family...for our sisters and daughters. http://www.startribune.com/lifestyle/health/17313309.html Fasting may help cancer treatment Healthy cells that don't receive nourishment for a few days become more resistant to stress, study finds. Last update: April 4, 2008 - 7:45 PM Starving mice for a few days before chemotherapy protected their healthy cells from damaging side effects, offering a possible way to shield cancer patients from the debilitating hair loss, nausea and anemia that comes with treatments, researchers reported this week. The study in Proceedings of the National Academy of Sciences could also allow the use of higher chemotherapy doses without endangering patients. Valter Longo of the University of Southern California, who led the research, said healthy cells deprived of nourishment stop dividing and become more resistant to stress. That makes them less vulnerable to chemotherapy, which targets cells that are dividing. Because cancer cells do not respond to their environment in a normal way, starvation does not protect them from the drugs, said Longo, who did the research with scientists at USC and Giannina Gaslini Institute in Genoa, Italy. The experiment looked at how healthy and cancerous cells reacted when they were exposed to toxins after being denied glucose, a simple sugar. Yeast cells, for example, were 1,000 times more resistant to damage from chemotherapy than yeast cells containing a tumor gene. An experiment in mice confirmed the protective effects of fasting. http://www.physorg.com/news127996289.html Japan scientists identify enzyme that may suppress cancer Some cancer patients removing second breast WRAL Raleigh Play Video Video: New technology holds promise for predicting breast cancer recovery CBC.ca Play Video Cancer Video: Stimulus bill draws Kennedy back to Senate AP HONG KONG (Reuters) – Scientists in Japan have identified an enzyme which appears to suppress breast cancer and they hope the finding will spur new therapies to control the second most common cancer in the world. At issue is the enzyme CHIP, which experts say can stunt cancer growth by degrading a number of cancer-causing proteins. The enzyme occurs naturally in human breast tissue. In an article published in Nature Cell Biology, the scientists said they injected two kinds of human breast cancer cells into mice. One set carried the CHIP enzyme and the other was without the chemical. Tumors in the first group of mice with the CHIP enzyme were far smaller than the one without the enzyme, Junn Yanagisawa at the University of Tsukuba's Graduate School of Life and Environmental Sciences in Japan told Reuters. The same results were seen in a parallel experiment using a more aggressive line of human breast cancer cells, he added. http://news.yahoo.com/s/nm/20090209/sc_nm/us_cancer_breast nephrogenic systemic fibrosis mimicking inflammatory breast cancer Nephrogenic Systemic Fibrosis Mimicking Inflammatory Breast Carcinoma By Solomon, Garron J; Wu, Elizabeth; Rosen, Paul Peter * Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing dermopathy, is a newly recognized systemic fibrosing disorder primarily affecting patients with chronic renal failure. Patients with skin involvement often develop papules and plaques with peau d'orange surface changes. The lower extremities and trunk are most commonly affected. The most important histologic differential diagnosis is with scleromyxedema. To our knowledge, we report the first case of nephrogenic systemic fibrosis involving the breasts of a 61-year-old woman with end-stage renal disease, clinically mimicking inflammatory breast carcinoma. We propose that nephrogenic systemic fibrosis be considered in the differential diagnosis as a rare possibility when cutaneous changes in the breast suggest inflammatory breast carcinoma in a patient with renal failure. (Arch Pathol Lab Med. 2007;131:145-148) Nephrogenic systemic fibrosis (NSF) is a recently described systemic fibrosing disorder primarily affecting patients with chronic renal insufficiency. Although the exact cause is unknown, bone marrow-derived circulating fibrocytes are suspected to be involved in the pathogenesis of this rare condition. Skin involvement in NSF frequently presents on the extremities as erythematous papules or plaques, often with peau d'orange surface changes and woody induration. Truncal involvement is less common, and breast involvement has not previously been reported. We report here a case of a woman with advanced renal disease who presented with bilateral breast swelling leading to the clinical impression of inflammatory breast carcinoma. Biopsy of one of the breasts revealed NSF. REPORT OF A CASE The patient is a 61-year-old woman with end-stage renal disease on hemodialysis who presented with tense swelling and ''dimpling'' of both breasts. The patient's medical history also included diabetes mellitus, hypertension, asthma, and hypercoagulability, with a recent thrombectomy performed for a left arm thrombosis involving her arteriovenous shunt. The patient was taking many medications including epoetin alfa. The patient's only significant laboratory findings were an elevated creatinine (10.2 mg/dL), a mild normocytic normochromic anemia (hemoglobin, 11.0 g/dL), and mild thrombocytopenia (platelet count, 140 10^sup 3^/µL). She had no palpable breast mass on physical examination. The clinical impression was inflammatory breast carcinoma, for which a biopsy was performed. The referring pathologist noted ''an infiltrating pattern of fibroblastic cells'' and submitted the slides for consultation to rule out fibromatosis. MATERIALS AND METHODS Clinical information was obtained from patient records. The diagnosis was based on examination of histologic sections stained with hematoxylin-eosin. Stromal mucin was demonstrated with the Alcian blue histochemical procedure, and CD68-reactive and CD34- reactive cells were identified by immunohistochemistry using a standard avidin-biotin method. PATHOLOGIC FINDINGS The excisional biopsy specimen of the left breast measured 5.0 4.0 1.0 cm with an attached skin ellipse measuring 5.0 1.0 cm. The microscopic sections showed marked thickening of the dermis with accumulation of thick collagen bundles separated by clefts in the papillary and reticular dermis (Figures 1 and 2). There was focal extension into the subcutaneous tissue along thickened fibrous septae. Within the dermis there was a laminar proliferation of small blood vessels surrounded by a predominantly plasmacytic infiltrate (Figure 3). Higher magnification of the collagenous stroma revealed an increased number of spindled cells resembling fibroblasts and increased stromal mucin (Figures 4 and 5). The stromal spindle cells were largely CD68- positive and CD34-positive (Figure 6, a and b). COMMENT Nephrogenic systemic fibrosis is an emerging disease principally affecting individuals with advanced chronic renal disease.1 It has also been associated with chronic hepatic disease and the hepatorenal syndrome.2 The scleroderma-like cutaneous manifestations of this clinicopathologic entity were first recognized in 1997 in a cohort of renal dialysis patients and reported by Cowper and colleagues3 in 2000. The term nephrogenic fibrosing dermopathy (NFD) was introduced in 2001.4 Subsequently, an autopsy performed on an individual diagnosed with NFD revealed fibrosis of the diaphragm, psoas muscle, renal tubules, and rete testis, suggesting that the fibrosing disorder was not limited exclusively to the integument.5 Additional reports demonstrated that the lungs, heart, and skeletal muscle can also be affected, 6,7 and as a consequence, the preferred terminology is now NSF/NFD. CancerCare Assist® We know the financial burden of cancer can be great. So, for more than 60 years, we have provided limited grants for certain expenses related to treatment. Our financial assistance program is one of the longest running and best regarded in the country. In order to qualify, you need to provide CancerCare with information about your income, savings and expenses, and in some cases provide invoices for the cost of service. Your healthcare professional must also provide information on your cancer. Download our financial assistance application in English or en español . Please be aware that our grants are not for basic living expenses such as rent, mortgages, utility payments or food. If this is the kind of assistance you need, please call or visit your local United Way for information on local resources that can help. Below is a description of our programs available to people nationwide. Please contact CancerCare at 1-800-813-HOPE (4673) for more information. Breast Cancer 0. AVONCares: Limited financial assistance for homecare, childcare and transportation. A program in partnership with the Avon Foundation. 0. Linking A.R.M.S.™: Limited financial assistance for hormonal and oral chemotherapy, pain and anti-nausea medication, lymphedema supplies and durable medical equipment. A program in partnership with the Susan G. Komen Breast Cancer Foundation. All Cancers (excluding the above) Limited financial assistance for men and women for homecare, childcare, transportation, and pain medication. Includes the Touching Hearts program funded by the Mary Kay Ash Charitable Foundation and San Diego area assistance funded by the WebMD Foundation. Children (ages 18 and under; all cancers) Limited financial assistance for homecare, childcare, transportation, medication and copays. This program has been funded by many generous individual donors. This page can be found at: http://www.cancercare.org/get_help/assistance/cc_financial.php Cancer Care, Inc._1-800-813-HOPE (4673) - www.cancercare.org CancerCare is a national nonprofit organization that provides free, professional support services for anyone affected by cancer. We are busy with our heads in the books trying to understand estrogen and detoxification. We do feel that there is convincing evidence that a. You can remove toxic chemicals from your body b. You can influence whether the chemicals you are exposed to do more damage by using nutrition as a preventative c. You can use nutrition to influence how estrogen is behaving in your body. Over the nest few months, we will attempt to lay out some evidence. Let us know what we are missing and what you are thinking about this info. This month, we published a talk by naturopath Connie Hernandez about detoxification. Dr Hernandez was great in getting the entire picture of not only body detoxification, but also mental and spiritual issues. Her article is posted here. http://www.breasthealthproject.com/DetoxificationforBodyMindandSoul.html Since Dr Hernandez started talking about estrogen testing, we took on the issue a bit and published a "101" page on it. http://www.breasthealthproject.com/EstrogenMetabolites.html On the blog this month we put all the evidence from the past six months that is coming out about how nutrients are protecting from cellular or DNA damage. Well, probably not all, let us know what we may have missed. http://www.breasthealthproject.blogspot.com/ Last month we attended the Annie Appleseed Project conference on Cancer and integrative/alternative medicine. If you did not go, DO NOT MISS IT next year! Not only was the food actually nutritious a first for any cancer conference we have been to, but the information was outstanding. Read more here and look for our interviews with amazing knowledgeable clinicians to be published in the next few months. http://www.breasthealthproject.com/AnnieAppleseedConference.html Men With Breast Cancer at High Risk of Second Tumor THURSDAY, Jan. 25 (HealthDay News) -- Men who have breast cancer have a significantly increased risk of a second cancer, according to the largest study ever done on the subject. "We looked at the risk not only of a second breast cancer but also of other cancers. We found the risk of other cancers increased as well," said lead researcher Hoda Anton-Culver, director of epidemiology at the University of California at Irvine. Her team published its findings in the February issue of Breast Cancer Research. Breast cancer remains rare among men. Only about 1 percent of breast cancers are diagnosed in men, but some 1,400 new cases are reported in the United States each year, according to the American Cancer Society. Because of the relatively small incidence of male breast cancer, "not one study until now has looked at large numbers," Anton-Culver said. However, "our study looks at a very large number of men," she said, "so there can be validity to large numbers of a rare cancer like this one." The researchers analyzed data from the California Cancer Registry on 1,926 men who developed breast cancer from 1988 to 2003. Of these, 221, or 11.5 percent, went on to develop a second cancer at least two months after their breast cancer diagnosis. One significant second cancer in the group was malignant melanoma, with an incidence that was 50 percent higher than normal, she said. There was also an elevated risk of stomach cancer. There are several possible explanations for the increased risk, Anton- Culver said. It might be due to the side effects of treatment of the primary breast cancer, for example. But the most probable cause is genetics, she said, with the men being at "higher risk of developing cancer in general." And studies by the group have shown a high incidence of a breast cancer-related gene, BRCA2, in the men, Anton-Culver said. The findings could have a very practical application in terms of screening, she said. Her group has been collecting family histories of men with breast cancer, in collaboration with British researchers. "We definitely do see an association between breast cancer in men and an increased risk of being a carrier of a cancer-related gene," Anton- Culver said. That relationship indicates that a screening program looking at close relatives of men with breast cancer could help with the early detection of malignancies, she said. "Once you have a man with breast cancer, you have a great target for screening," Anton-Culver said. For more on male breast cancer, go to the U.S. National Library of Medicine. Story By Ed Edelson HealthDay Reporter This Man Survived Breast Cancer Ted Allen Esquire Magazine, August 2000 In "This Man Survived Breast Cancer" contributing editor Ted Allen sheds some light on a virtually unknown killer, male breast cancer. "Hardly anyone is aware that men can get it--not even most doctors," says Allen, who, together with executive editor Scott Omelianuk, also authors the periodic Things a Man Should Know column and the eponymous series of books, the latest of which is Things a Man Should Know About Marriage (Riverhead Books). "When I first looked into this disease, had trouble finding anybody who could talk about it, because there is precious little data about this type of cancer and virtually no information about the social issues surrounding it," says Allen. "But when I did find some men who are struggling with it--through an Internet news group--information just started gushing in I think that attests to the frustration that a lot of these men feel--that there's so little support for them out there. It was a privilege to hear their stories." This year in America, fourteen hundred more will learn they have it. All of them will be shocked and dumbfounded. And some of them will die. This is a story about numbers. And then, decidedly, it is not. The first of these numbers is seven: one man plus one woman plus four kids plus a dog named Happy. You pull out of Portland, Oregon, that misty and muscular little city bisected by the Willamette River, that town of rain and Powell's Books and gold-rush hotels with Wild West murals in the lobby, and you point yourself toward the Pacific. Past the Intel plant on Highway 26, where they developed the new one-gig Pentium chip, code name Coppermine, down the littered byways of Exxon and Wendy's and Safeway, could be anywhere, U. S. A., and it is. And then, about twenty-two miles outside town, you're or Pacific Avenue in the suburb of Forest Grove, and you're turning in to a trailer park, and the street is wide and clean, and the yards are landscaped- -one garden has painstakingly sculpted spiiral topiaries--and there are those rows and rows of mailboxes nailed neatly to planks and mounted on poles, must be a hundred or them. And you stop in front of a blue double-wide, number 68, with a line of rosebushes cut back for the winter and a vine-covered trellis and a varnished cypress sign hanging by two little chains from the porch roof. And into the sign has been routered, in cursive, the words "Lyons' Den." This is the home of Dave and Teresa Lyons. And you find, after knocking on the door and being admitted to the cozy living room by a seven-year-old in his pj's and a two-year-old Labrador-spaniel mix, a big, loving, chaotic family. There's the two foster kids (eleven and four), whom we'll call Melinda and Jack. There's Jacob and David, their natural-born sons (nine and seven). There's Ashley and Raymond, whom the couple is watching so their mother can go to work. Six kids and a puppy. Three bedrooms. One paycheck. There are Sounds of computer games, barking, and occasional shrieks of toddler outrage; there are shelves sagging with National Geographics and videos and toys; there's Dave's collection of Hot Wheels cars--he especially favors purple ones. There are Olan Mills portraits of Jacob and David arranged stair-step on the wall, both looking left and upward, toward a third portrait: Jesus. And on a blue love seat, the closest thing to a sofa that will fit in the crowded room, sit Dave and Teresa. Dave has positioned his right arm upon the back of the sofa, with his forearm hoisted skyward. He flexes his fingers as if he's crunching a squeeze bulb. He does this with his arm, with the squeezing, for hours on end. David Bayne Lyons is thirty-six years old. He is soft-spoken and gentle, and he radiates a goofy sense of humor. He's possessed of a boyish aspect and wiry, thinning black hair, wears blue jeans and a purple T-shirt and glasses and Nikes. He grew up in Fremont, California, where his father was an electronics technician and his mother served it up in school cafeterias. He and Teresa were married in 1986 in a quickie chapel in Reno--the kind of place where you return the plastic bouquet after the ceremony--and kept it a secret until they could seal the deal with a church wedding later that year. "We tied a double knot," says Teresa, "so it won't come untied." They are both devout Seventh-day Adventists, and they eat no meat and neither smoke nor drink. Dave works in the class- 1 "clean room" at Intel, where you will find only one half-micron of dust per cubic foot. There, in a white Gore-Tex bunny suit (that's what he calls it: his "bunny suit"), he cranks out the microchips that have powered the nation's techno-revolution. "Mostly what we do is we put the wafers on the machine and push start," he jokes. They are the most regular of American families, a loving family, a salt-of-the-earth, giving sort of family, as you can plainly see, and things are pretty good. But it's been rough these past three years--very rough. The warning signs, .they came way, way back. Back when Dave was just a teenager. And the signs, despite Dave and Teresa's desperate efforts to get answers, they were flat-out ignored.Breasts. You should know that despite your possession of a Y chromosome, you have them. Two of them, most probably. They may not be perky or pendulous; nobody is likening them to peaches or proposing to shake your tree. But you have them. Call them pecs if you like, but your pectoral muscles, the ones that power your lateral arm strength, facilitating push-ups, the ones that wrap around your rib cage, those are just part of the picture that makes up the larger entity we know as your chest. On top of those muscles is fatty tissue. That fatty tissue, between the muscles and the skin- -those are breasts. Your breasts. See, there was this lump. In Dave's chest, right side. Painless at first. He mentions it to his doctor, who assures him it is a cyst, or something or other. Boys get those in puberty, they go away, don't give it a second thought. So he never gives it a second thought. Not until quite a few years go by. Not until the day in early 1990 when he is driving to work and notices that his shirt is sticking to his chest, wetly, on the right-hand side. He reaches down, checks, sees red on his hand. He reaches again and squeezes a little, to ascertain whether the fluid is coming from where he thinks it is coming from: his nipple. It is. After work, he brings it to Teresa's attention. She looks. He squeezes and more pinkish fluid comes out. Oh, my God, she thinks. What's happening? Something takes shape in her stomach; she will later describe it as a heavy ball of dread. She wipes away the fluid with a tissue. The doctor sees him a week later and forwards him to a specialist in breast diseases. What the specialist in breast diseases tells him: Don't give it a second thought. This pattern will persist, with each new job and each move and each insurance change and each new GP-- four doctors, eight years, a mantra of blithe reassurance. And eventually, Teresa says, the pooh-poohing from one medical professional after another takes hold and causes the ball of dread to shrink, to recede. And then, in late 1997, Lyons is roughhousing with his boys, and he finds himself pushing them away from his right side because somewhere along the line, pain has come into the picture--a throbbing ache that radiates from the pectoral area to the right arm. And then there's that dinner at Round Table Pizza, which features a play structure for kids; one of the tots drops a toy between the play structure and a wall, and Dave, reaching for it, brushes the right side of his chest against a sharp corner. "The only pain I can think of that comes even close," he recalls, "is getting hit in the testicles." And Dave is worried. And Teresa is worried. And this time, they resolve, something is damn sure going to be done. An appointment is made, and Dave drives to a clinic. There he is told to put on a gown, open to the front, which feels strange. He's a man, after all, he goes to the swimming pool without a shirt; why not here? But he complies. Perhaps you're not aware of this: A mammogram is achieved by stepping up to a machine with a hard plastic clamp, a sort of vise. The breast is pulled into the clamp by a technician and held there. The clamp then squeezes down, flattening the breast so that it's thin enough to produce a clear X-ray picture. The clamp is rotated, the breast is compressed again, and another picture is taken. This can be done with a man as well as with a woman, but unless you're a man with some meat on you, it's difficult to get much into the clamp. Also, as any woman who's ever had one can tell you, it hurts. The technician pulls as much of Lyons as she can into the clamp and compresses until her hand will no longer fit between the plates, down to about half an inch. She notes that his is the hairiest chest she has X-rayed in some time. They laugh. The crack makes Dave feel a little better. After the X ray, there is an ultrasound. And the radiologist tells Dave he does not like the looks of this thing. Not at all. This thing, he tells Dave, it measures 2.2 centimeters. It has edges that are bumpy, like a piece of cauliflower. Garden-variety cysts don't have edges like that, plus, they're hollow, with fluid inside. This thing, he says, it has blood vessels in it.Talking with Dr. Patrick Borgen is like chasing a felon on a perp walk. He can squeeze in a meeting only on foot, striding from one appointment to another at Memorial Sloan-Kettering Cancer Center in New York. So much cancer, so little time--Borgen seizes his days at six or seven in the morning, stretches them to eight or nine at night, toils weekends. Most cancer doctors live like this. He has a house in the fancy-pants suburb of Bedford, New York, around the corner from Paul Shaffer; doesn't see much of home, though. His kids attend school with Glenn Close's kids. He's been profiled in Biography's magazine, and he's been a guest on the Today show. Borgen is the breast-service chief in Sloan-Kettering's department of surgery. He is a nationally recognized authority in the field of breast cancer at one of the nation's best cancer hospitals. He has seen thousands upon thousands of breast-cancer patients since the 1980s and has saved thousands of their lives and has lost many, too, and of these thousands upon thousands, about 140 of these breast- cancer patients were men. You are surprised to learn that men can develop breast cancer? That selfsame disease that ravages millions of women the world over? You did not know this? Don't feel bad. Your doctor doesn't know, either. Even breast specialists don't always know, as Dave Lyons learned. In his entire lifetime of practicing, chances are, your general practitioner might identify one case. He will be shocked and astonished. He will telephone his colleagues. He will not know what to do. Why this uncertainty, this lack of information? Simple, really: "You look for common things, commonly," says Portland oncologist Ralph Weinstein. "Men, they feel a lump, they don't know they can get breast cancer, they go, they see their doctor, he doesn't know men can get breast cancer," Borgen says. "Their doctor tells them, `Well, let's see if it goes away. Come back in six months.'" By the numbers, from a particular way of looking at public health-- and this is a story about numbers--male breast cancer is a completely insignificant disease. More than 180,000 women will be diagnosed with breast cancer in the United States this year. Forty thousand will die. By contrast, the number of men who will contract the disease is about fourteen hundred, with four hundred fatalities. More people are killed by falling off roofs or scaffolding each year. If Borgen's sample of 140 patients sounds small, it is, though it's also more male breast-cancer patients than any other facility in the United States has treated. So is this yet another damned disease a man needs to worry about catching? Not really. Not much. But a little. When boys and girls are still in the single digits, their breasts are essentially the same--undeveloped ducts just under the nipple and areola. At puberty, girls' ovaries produce hormones (notably estrogen) that cause the ducts to grow and lobules (milk glands) to form at the ends of the ducts. The lack of estrogen prevents this growth from happening in boys. But they retain those vestigial, atrophied ducts. Women have vastly more breast cells than men, which is part of the reason why they're much more susceptible to breast cancer. But men aren't home free, particularly men with a family history of breast cancer (even among female ancestors) and men with the common disorder gynecomastia (an enlargement of the male breast) or the rare genetic condition Klinefelter's syndrome. Age is also a risk factor (most patients are diagnosed in their fifties and sixties), as are exposure to radiation, liver disease, and estrogen treatments, such as those used by prostate-cancer patients and transsexuals. The causes of breast cancer, as with most cancers, are not firmly known. Some breast cancers are related to inherited mutations of the genes that suppress tumors. Estrogen and other hormones are thought to play a major role; most breast cancers feed on these hormones. Ironically, the whole reason Borgen became interested in male breast cancer in the first place was the potential such research into hormonal differences between the genders could offer. The good news: Male breast cancer is often easy to detect. It always occurs immediately behind the nipple, in the milk ducts that, because men are men, never develop. So that's where you look. (In women, cancer can occur behind the nipple, but far more often it strikes in the upper lobes of the breast, closer to the arm.) Sometimes male breast cancer causes inversion of the nipple. It may cause bleeding there, too, although that happens in only about 20 percent of cases. "A bloody nipple discharge in a man who hasn't had any history of trauma is breast cancer about 90 to 95 percent of the time," says Borgen. Yet, harmless cysts are common enough that it hardly makes sense to go around mammogramming and biopsying every guy who comes into the doctor's office complaining about a bump (numbers, yet again). What's needed is something simpler: for more doctors to become at least dimly aware of a constellation of symptoms. You figure, male patient, in his fifties or sixties, family history of cancer, painless mass behind a nipple, gynecomastia, let alone nipple inversion or bleeding--"these should all play a role in someone's index of suspicion," Borgen says. All of the above, he says, "that should set off a lot of bells, buzzers, and whistles." That's all.Dave and Theresa spend Thanksgiving 1997 with Teresa's parents. They feel no need to mention the impending surgery, basically an investigative lumpectomy. It is scheduled for December 9. The surgeon is in no particular hurry. On D-day, the doc is almost jolly, despite his conviction that the Lyonses are wasting their time and, more important, his. He performs the lumpectomy. Local anesthetic. Dave feels no cutting, no pain; he does feel a touch of nausea, a tugging. He hears these sounds: the suction machine, the snipping of scissors, the clanking of instruments on a tray. The proceeds: a lump of flesh, size of a grape. It's a dull word, lump, suggesting something stupid, inanimate. Another term, mass, feels similarly vague, faintly threatening, maybe, but clinical. Growth, that's worse than mass. Cyst sounds like something disgusting on your toe that doesn't belong, but harmless; something that's removed and forgotten. And then there's tumor. "Oh, yeah; this is fine," the surgeon says. "I'll be able to tell you this is not cancer." Seven days pass. On December 16, there is a chemical spill at the Intel plant. Dave, being a member of the emergency-response team, dons a protective suit and helps clean it up. Wearing the suit causes a man to sweat prodigiously, so when the job is done, Dave's supervisor sends team members home for a shower. Dave reaches the trailer about noon, scrubs up, and sits down at the kitchen table with Teresa. It is a pleasant surprise for her; Dave rarely comes home in the middle of the day. The phone rings; Teresa answers. It is a man. He asks for Dave. It is the surgeon. "And so I handed the phone to Dave and I just collapsed in a chair," Teresa says. "Dave sat down and his face just turned white, I mean white as a sheet. If I could have sunk down any more, if I could have fallen off the chair--I was just in shock. I didn't even have any words. I couldn't cry. I was just too ... too shocked to cry, I guess. And I said, `It was cancer?' And he goes, `Yes.' And we just sat there looking at each other. "I said, `Honey, you can't go back to work.' He said, `I have to. What am I gonna do? Sit around here and mope all day?'" Teresa tried hard not to start crying. They stood there hugging each other for probably five minutes. And he said, "I have to go." You can't even describe the awful sick feeling you have, the sinking feeling, like a ship is going down," Teresa says. "And I thought, Oh, my God, he's gonna die. And there's no way I can raise my kids on my own. The kids are playing; how do you explain to them that Daddy's got cancer? All we knew was that they didn't get it all. There was still more there. The margins had been positive." The second surgery, a modified radical mastectomy, comes without delay this time. It takes three and a half hours. The lymph nodes feel unusually large, the surgeon tells Teresa. You better pray there wasn't cancer in those nodes, he tells her. When the nurse removes the bandages the next morning, a huge flap of skin comes off with them. On the right side, Dave's chest is not just flat; it's deeply indented, purple and red from the trauma, staples and sutures everywhere, two eliptical scars coming together and trailing up to e armpit, from which a clear tube drains fluid into a bulb. After a time, the doctors and nurses leave. Dave and Teresa are shocked and angry; the wounds look sloppy to them. "They took my nipple, Dave says. The surgeon hadn't mentioned that. There was a time not long ago at all when male breast cancer was commonly treated with a procedure called orchiectomy--the surgical removal of the testicles, or castration. Theory was, scale back the level of male sex hormones in the body, upon which many cancers greedily feed, and the tumor will regress. It works. Happily, they can do that sort of manipulation now with drugs. But nearly any man who develops breast cancer will need a mastectomy, the removal of all the offending breast tissue, the nipple, and the areola. Of course, cancer is often not content to stay put. If it metastasizes through the lymphatic system, the body's "pool filter" network, which drains upward from the breast through a string of lymph nodes under the arm, those nodes must come out, too. And when you take out enough nodes under an arm, a condition called lymphedema can result, in which the lymphatic fluid that accumulates in that arm has no nodes to escape to. The arm swells, sometimes painfully, making manual work difficult. There's no cure, just massage techniques and compressive bandages that help force the fluid back out of the arm. For many men, of course, the surgery is just the beginning. There's chemo and radiation, too. Lyons was lucky enough to dodge those bullets, but he got a nasty case of lymphedema--that's why he holds his arm skyward on the back of the couch, flexing his hand, squeezing the lymphatic fluid back into his torso. Considerably worse, both for him and his family, have been the side effects of his primary medication. Four weeks after his mastectomy, Lyons sees his oncologist for the first time. The prescription: tamoxifen, a frontline treatment for breast cancer that blocks cancer-cell receptor sites for estrogen, upon which they would otherwise feed and grow. The drug is effective for many people, but it can cause serious side effects in men: depression, hot flashes, sleep problems, lack of libido, impotence. "We read that the-loss of libido was awful," Teresa Lyons says, "but the worst part were the mood swings and depression." Dave rubs his eyes; his left hand shakes slightly. "It's been pretty hard on my family," he agrees. Nine months into the drug therapy, Teresa's parents are visiting, staying with the Lyonses in their crowded trailer. Teresa's mom ignores Dave's pleas that she stop cleaning, scrubbing, washing. He blows up. "He told her that he didn't like having her in our house, and that she needs to mind her own business," Teresa says. Mom starts crying. Dave rips his arm from Teresa's grasp and runs out of the house into a frigid night. In a T-shirt. Half an hour later, she finds him pacing the block, still seething. Around the same time: Tough day at the plant, nothing's going right, and the emergency-response team is paged to perform an emergency drill. Lyons goes ballistic. He peels the ERT sticker from his employee badge, storms up to his supervisor, smacks the sticker onto the supervisor's chest, and hollers, "I don't have time for this crap!" "I don't talk to anybody that way," Dave says, "much less my supervisor." You've got to get this taken care of, Teresa says. You're going to lose your job, she says. You're going to ruin our lives because of your anger. The doctors up his dosage of Paxil, an antidepressant, and Lyons evens out pretty well. "He's still hotter under the collar than he ever was," Teresa says, "but it's under control now." And his prognosis? As with any man, it should be no worse than it would be for a woman. The previously held notion that breast cancer is more deadly in males turns out to be largely a function of delayed diagnosis. Of medical ignorance. When that lack of knowledge is surmounted, male breast cancer is exactly the same disease. "If you correct that delay," Borgen says, "then the disease is every bit as curable, as treatable, as female breast cancer is." Dave had a long, long delay in diagnosis. "There should not be a reason why men have an inferior chance for cure than women," says Dr. Weinstein. "If it's done right."The day breaks clear and chilly on the banks of the Willamette on September 27, 1998, and at 7:00 A.M. the Lyons family arrives in downtown Portland for the Susan G. Komen Foundation's 5K Race for the Cure. There are thirty-three thousand people there. Weeks prior, they had been told that Dave could not compete because, by acclamation of the foundation's members, the race is a women-only event. "We're bosom buddies," a member told Teresa. Dave, clearly, is bosom free, but Teresa is not sitting still for this. She scores two and a half hours on a local radio call-in show. The host, Lars Larson, is outraged; the callers fume. The foundation is embarrassed. Dave is extended an invitation to run as an "honorary participant." The "honorary" thing galls him and Teresa, but they show up, albeit with chips on their shoulders, and they bring more than $200 that they've raised from friends and neighbors and people from church. Dave still has to tussle at the sign-in table to get his hands on a competitor's shirt and cap emblazoned with SURVIVOR--the volunteers want to give him a different shirt, the kind worn by spouses. He wins out. When Dave was first diagnosed, he recalls, "I was too embarrassed to tell anyone." Now, at the race, he elects to keep the shirt untucked. "If anybody bugs me about it," he vows, "I will pull up my shirt and show 'em!" Along the route, a few of the onlookers point at Dave. Some snicker. The Komen Foundation is a hugely successful operation--there are now 109 cities hosting Race for the Cure--and is obviously a well- meaning one. But its raison d'etre, like that of the entire breast- cancer system--research, fundraising, public relations, psychological support--is breast cancer in women. The movement has been incredibly effective. Borgen calls it the strongest lobby in the country, stronger than the NRA. But it appears unprepared to deal with the 1 percent of cases that happen to be male. Recently, the John W. Nick Foundation, named for a Wall Street broker who lost his life to breast cancer, created a ribbon honoring both men and women with the disease (it's pink and blue), but few have ever seen it. Dave and Teresa Lyons felt so alone in their struggle that they launched a support group, the Male Breast Cancer Awareness Group, in Portland, one of the few anywhere in the country. Its first meeting was in October of 1999. No such endeavor has yet to take wing anywhere near East Windsor, New Jersey--at least not to Bill Sherman's knowledge. Sherman, a high school guidance counselor, naturally felt shocked and frightened when he was diagnosed with breast cancer in 1996, and so he sat in on a women's group. "And I was--I don't want to say shunned, that's a strong word," Sherman recalls. "But I never felt welcomed. I just didn't feel welcomed, so I didn't go back." Even if there were more men's groups, there's that peculiarly male tendency toward stubborn self-reliance and insecurity at play here, too. "Women pick up the phone and call fifty other women," says Borgen. "They network, they say, `Oh, I know a good radiation guy, I know a good surgeon, I know a good acupuncturist.' Men don't do that; men sit at home. It's almost like asking for directions; men just don't do it." Sherman is asked if he's ever met another male patient. "Met?" he asks. "Uh, no. Nope. I'm on the Internet, but I have not met any." Back at the 5K race, Dave makes it to the finish line, where the woman who is supposed to record his time won't take his ticket. "Are you the person who's supposed to take this?" Dave growls. "Sor-ry," the woman says sarcastically. The fact that the fight against breast cancer has become something that women own is in large part a function of the fact that they have every right to own it. Just not entirely. "I had women telling me, `We don't want men in this group; it's a woman thing,' "Teresa says. "I mean, even before the race was half over, we were feeling defeated. I didn't even want to turn in the money." But they did turn in the money. And Dave got a prize. And a short time later, they got a vastly better reward. The best possible reward. The most meaningful, inspiring, exciting outcome possible. Which is to say, through their actions, they quite possibly saved a man's life.Eugene, Oregon, is about two hours south of Portland. It has long been something of a hippie haven; during the anti-WTO brouhaha in Seattle, Eugene activists staged their own boutique protest downtown. Richard Gilbert, though, he watched the protests on TV with something of a gimlet eye, being that he's not a hippie; he's a sixty-six-year-old real estate broker who nurtures seventy-year-old, holly trees and drives a twenty-year-old Benz. He's also more your typical candidate for breast cancer than Lyons, being rather a large man of more advanced years. My daughter says, `Dad we've already decided you re gonna die of a heart attack, not cancer,'" Gilbert cracks. "She's very candid." Also, Gilbert suffers from a case of gynecomastia, a risk factor for the disease. In late September of 1999, Gilbert was carrying his wife s sewing machine up a flight of stairs and bumped it against the left side of his chest. It hurt. Shortly thereafter, his wife, Nancy, recalls, he went to his doctor on a routine matter and mentioned the chest pain. "And the doctor said, `Well, let's just watch it.'" Three weeks later, the Portland Oregonian published a small story about Lyons's dustup with Race for the Cure. The story got picked up by the Eugene Register-Guard on October 7. Gilbert read it over breakfast and faxed it to his doctor. The next day, the mammogram. "They squeezed the hell out of me," Gilbert says. On October 12, the ultrasound. "Nodular palpable abnormality just to the ten-o'clock position of the left nipple," the radiologist wrote of the tumor, about the size of a pea. "Should be biopsied ... suspicious for malignancy." It was. And it was. On October 29, the modified radical mastectomy. Nancy, it should be noted, is not Richard Gilbert's first wife. The woman he was married to before, Roxy, died of brain cancer. Her deterioration lasted five years. In part because of that, Nancy imagines, her husband decided to act early. Still, the improbable activism of the Lyonses can't be overlooked. Because the mild-mannered couple--hardly political rabble-rousers-- were hell-bent on participating in a women-only event and because they formed a support group and got their story into Gilbert's local paper and because he saw it and faxed it to his doctor, a malignant tumor was detected and removed. "I think we might have made a difference for a few people," Teresa allows. Gilbert's lymph nodes turned out to be clean. He now will check in with an oncologist every three months for the next two years, every six months for three years after that. "I feel like I've been reborn because of this experience," Gilbert says. After his surgery, he drove up to visit the Lyonses. He brought them an azalea and Morsecode flashlights for the boys. It turns out that Gilbert also is a Seventh-day Adventist. Coincidence? "That might be the wrong word," Lyons says.It is now late February 2000. A Thursday. Dave Lyons gets in his 1986 Chevy Celebrity and drives forty minutes to the oncologist, as he must do every three months. And afterward, he is advised that he has reached something of a milestone: He remains clear, and now, for the next three years, he need go only every six months. Lyons is incredibly fortunate, relatively speaking. Despite the fact that his cancer had a generous number of years to riddle his body unperturbed, his doctors believe it did not spread. "I believe that I was healed," he says. Of course, faith would be meaningless if it were easy. "That fear, it's always there," Teresa admits. "This could show its ugly head again. We believe he was healed, but we also know that--reality--that it could come back." Little Jack, the four-year-old, interrupts for the umpteenth time and approaches Dave's knee. The boy's been living in their home for only a week; already, he's calling them Mom and Dad. "Dad," Jack wants to know, "where are my socks?" "I don't know," Dave says. "Where'd you take them off?" "I took them off in the bedroom." "Well, they must be in the bedroom, then."Ten Names. Ten men. TEN NAMES. Men who are fighting or have beaten this disease--to the extent that one beats cancer--and who shared their stories with us: Bob Riter, Ithaca, New York; Bob Jones, Yardley, Pennsylvania; Denton Ortman, York, Pennsylvania; Sam Hurwitz, Spokane; Charles Blosten, Littleton, Colorado; Stephen Meredith, Woodinville, Washington; James Lowery, Cordes Lakes, Arizona; Hellmut Golde, Seattle. And two more in the Portland support group: Bob Miller and Lowell Gere.This is a story about numbers. Five-year survival rate for men with breast cancer with no metastasis: 90 percent. Five-year survival rate when spread to regional lymph nodes: 75 percent. Five-year survival rate with distant spread: 20 percent. Relative delay in diagnosis of men versus women: eighteen months.The Numbers Results from an informal, non-scientific survey of 104 male breast- cancer patients treated at Memorial Sloan-Kettering Cancer Center, New York, between 1984 and 1999: * Percentage of patients who, prior to diagnosis, were unaware that men could develop breast cancer: 86 * Percentage of patients who were not diagnosed until they had sought a second opinion, often because the initial physician was uncertain of what he was seeing and asked the patient to do so: 77 * Percentage of patients who confined specific discussion of their diagnosis to immediate family: 20 * To family and very close friends: 60 * Percentage of patients who felt "significant" embarrassment at being diagnosed with a disease typically considered to affect only women: 40 * "Some" embarrassment: 15 * Percentage of patients who were frustrated by the lack of community support mechanisms for men: 80 Question: What was the most frustrating part of your diagnosis and treatment? Answer: Overwhelmingly, patients felt frustrated by the lack of information in the press and on the Internet concerning male breast cancer, and by the lack of other men with whom they could discuss their situation. FOR MORE RESOURCES: http://www.ibca.net/online_resources/male_breast_cancer.php Cancer cells spread by releasing 'bubbles' A new fundamental mechanism of how tumour cells communicate has just been discovered by the team of Dr. Janusz Rak at the Research Institute of the McGill University Health Centre (MUHC) in collaboration with Dr Guha from the University of Toronto. The cancer cells are able to communicate with their more healthy counter-parts by releasing vesicles. These bubble-like structures contain cancer-causing (oncogenic) proteins that can trigger specific mechanisms when they merge into non or less-malignant cells. These findings could change our view on how cancerous tissues work and lead to major clinical innovations. They were published on April 20 in the on-line edition of Nature Cell Biology. The surface of some brain tumour cells has long been known to express a mutated version of what is called the variant III epidermal growth factor receptor (EGFRvIII). Although this factor is expressed only in a fraction of tumour cells, it has a major impact on the malignancy of the whole tumor. How could this cellular minority have such an important impact" This mechanism was still unknownŠ until now. This study shows that the mutated EGFRvIII triggers production of small vesicles that project from the cell membrane and that carry mutated copies of EGFRvIII on their surfaces. They were baptised "oncosomes." Surprisingly enough, this shows that oncoproteins are not always confined to the cell that produced them. In this case they even migrate! Oncosomes will migrate until they fuse with another cell, either healthy or benign tumoral. Oncogenic protein AGFRvIII then becomes integrated in the membrane of the "recipient" cell and starts stimulating specific metabolic pathways to make it act in an aberrant and malignant way. Although this may be a transient event, the changes could impact tumor behaviour by more rapid increases in cell numbers and by stimulation of blood vessel growth, hallmarks of malignant brain tumors. "With this information we can imagine that many mutant proteins are not necessarily confined to the cells that make them, but rather can migrate and spread around as cargo of oncosomes, a process that could be referred to as formation of the "oncogenic field effect," explained Dr. Rak. "It demonstrates that cancer is a multi-cell process, where the cells talk to one another extensively. This goes against the traditional view that a single 'mutated' cell will simply multiply uncontrollably to the point of forming a tumour. This discovery opens exciting new research avenues, but we also hope that it will lead to positive outcomes for patients." Indeed, the presence of oncosomes (containing EGFRvIII or other proteins) in blood of cancer patients could become a clinical marker, meaning that doctors could screen for a tumour's molecular characteristics instead of having to perform invasive surgery or biopsy. Currently, in the case of brain cancer, this very precise assessment cannot be performed without removing the tumour and therefore opening a patient's skull. However, the assay and analysis of oncosomes would potentially only require taking a small sample of blood or cerebrospinal fluid. This would be a step in ensuring patient comfort and choosing the best therapeutic strategy for them, factors that are key in the journey towards personalized medicine in a hopefully not-too-distant future. Reported April 25, 2008 Detecting Cancer at the Dentist's Office HOUSTON, Texas (Ivanhoe Newswire) -- Every two minutes, a woman is diagnosed with breast cancer. Every thirteen minutes, a woman dies from this disease. Early detection may be the key to surviving it … so what if finding out you had it could be as simple as going to the dentist? It could happen! It wasn't long ago, Resa Ott's life was threatened by cancer. "It takes the wind out of your sails and you don't want to die," Ott says. Had a double mastectomy. Now she's cancer-free. But her story is not unusual ... one in eight women will battle breast cancer in her lifetime and the battle against this disease has become personal for Dr. Charles Streckfus. "Cancer essentially wiped out my family," says Charles Streckfus, D.D.S., a professor of diagnostic services at the University of Texas in Houston. "My mother and father were killed back to back with cancer and left my sister orphaned, so it's somewhat of a grudge match." That why he's developing a test to catch breast cancer that can be given at the dentist's office. His idea is as simple as chewing gum! "It's very, very simple," Dr. Streckfus says. "It's extremely inexpensive. We get a gum base. You just chew it on a regular basis and then just spit it into a cup and after five minutes, we take the cup and determine what constituents are in it." Saliva from the gum is applied to a gold plated chip. A laser will give immediate results. Researchers at the University of Texas identified 49 specific protein markers that provide non- invasive diagnosis of benign and malignant breast tumors. "When an individual has cancer, a lot of the proteins are altered in saliva, so it could be a good bell weather instrument for presence of disease," Dr. Streckfus says. He warns this test is an early detection device … not a replacement for mammograms, ultrasounds or biopsies. But any woman who's had breast cancer knows … the earlier it's detected … the better! "I don't have mammograms any more, so for me to be proactive and chew a piece of gum and have someone say, 'You know, Resa, you're clear.' Oh, talk about peace of mind," Ott says. The diagnostic device is now being developed to be installed in dentist's offices. This saliva test could also be used to detect ovarian, endometrial, cervical and head and neck cancer. FOR MORE INFORMATION, PLEASE CONTACT: The University of Texas Dental Branch at Houston http://www.db.uth.tmc.edu http://publicaffairs.uth.tmc.edu/media/newsreleases/nr2008/bc-saliva.htm For information on Dr. Streckfus' research, contact: Cynthia Edwards Cynthia.Edwards@uth.tmc.edu Taking the Scary out of Breast Cancer Statistics Headline-grabbing reports citing alarming risk factors are often meaningless.By Carol Tavris and Avrum Bluming April 17, 2008 American women fear breast cancer more than heart disease, according to most studies, even though heart disease is responsible for 10 times as many female deaths every year -- and heart disease deaths exceed breast cancer deaths in every decade of a woman's life. Of women who are diagnosed early with breast cancer, more than 90% will survive, and most will not need disfiguring mastectomies or even chemotherapy. But the media understand how deeply women fear breast cancer, and the result is that every study that seems to find a link between some new risk factor and the disease makes headlines everywhere, captures public attention and stimulates the blogosphere into overdrive. Grapefruit is the most recent culprit. According to a study in the Journal of the American Medical Assn., eating a quarter of a grapefruit a day increases the risk of breast cancer by 30%. For many women, grapefruit immediately was toast. To assess these studies for their real-life implications, let alone for making decisions about our own behavior, the public needs to understand the difference between absolute risk and relative risk. If we tell you that the relative risk of breast cancer is increased by 300% in women who eat a bagel every morning -- Relax! It's not! -- that sounds alarming, but it is not informative. You would need to know the absolute numbers of bagel-eating breast cancer patients. If the number shifted from one in 1,000 women to three in 1,000 women, that is a 300% increase, but it's meaningless. If the risk had jumped from 100 women to 300, we might reasonably be concerned. In the large epidemiological studies that generally include tens of thousands of people, it is very easy to find a small relationship that may be considered "significant" by statistical convention but that, in practical terms, means little or nothing. For example, in July 2002, the Women's Health Initiative reported a 26% increase in breast cancer risk for women on hormone replacement therapy, which sounded worrisome. Even if that number were statistically significant -- and it was not, by the way -- this is what it translates into: The risk of breast cancer would increase within the studied population from five in 100 women to six in 100 women. We now have a fat file folder of all the studies we could find that have reported an association between some purported risk factor and breast cancer. Of these, the ones that got the most attention were three Women's Health Initiative reports. In 2002, investigators found an increased relative risk of 26% from using combined estrogen and progesterone; in 2003, it was 24%; and in 2004, the relative risk from using estrogen alone was minus 23% (suggesting it was protective against breast cancer). To put those findings in perspective, consider these published studies showing the increased relative risk of breast cancer from: * eating fish: 14% * eating a quarter of a grapefruit a day: 30% * gaining more than 33 pounds in pregnancy: 61% * being a Finnish flight attendant: 87% * being a Dutch survivor of childhood famine: 201% * using antibiotics: 207% * having a diagnostic chest X-ray: 219% * being an Icelandic flight attendant: 410% * using an electric blanket: 630% (but only if you are a black woman who used it for more than 10 years but less than six months in a given year). Why was there no call for Icelandic flight attendants to quit (or transfer to Lufthansa), for black women to use electric blankets for more than six months a year but only for nine years, for labeling antibiotics as carcinogens? Because these findings, which were improbable to begin with, were never replicated. In contrast, the increased relative risk of lung cancer from smoking is consistently between 2,000% and 3,000%. That's a finding that means something. Unfortunately, good news doesn't travel as fast as fear does. In 2006, the Women's Health Initiative investigators reanalyzed their data and found that the risk of breast cancer among women who had been randomly assigned to take hormone replacement therapy was no longer significant. Women assigned to take a placebo but who had used hormone replacement therapy in the past actually had a lower rate of breast cancer than women who had never taken hormones. This reassuring but non-scary news did not make headlines. Neither did the real findings from the March 2008 Women's Health Initiative report, which followed women in the sample who had stopped taking hormones for the previous three years. The researchers reported that the risk of cardiovascular events, malignancies, breast cancers and deaths from all causes was higher in the hormone-replacement-therapy group than in the placebo group even three years after stopping the therapy -- pretty alarming. But when we read the article closely, we saw that not one of the associations between hormone replacement therapy and breast cancer, or between the therapy and mortality rates from any cause, was statistically significant. Unfortunately, this did not stop the investigators from highlighting their negative findings as meaningful and troubling, and that is what most of the media picked up. No wonder the public, assaulted by numbers and frightening headlines, alternates between panic and cynicism. Physicist Richard Feynman once said, "If something is true, really so, if you continue observations and improve the effectiveness of the observations, the effects stand out more obviously, not less obviously." The association between hormone replacement therapy and breast cancer becomes less obvious with every study. We all want to understand the risk factors in breast cancer that are "really so," but to do that, we have to give up entrenched beliefs when the data do not support them, and look elsewhere. In the meantime, enjoy your grapefruit. Carol Tavris, a social psychologist, is a coauthor of "Mistakes Were Made (but Not By Me)." Avrum Bluming is a clinical professor of medicine at USC and a medical oncologist. ----------------------------------------------------------------------------------------- Erythropoiesis-Stimulating Agents May Not Be Safe for Cancer Patients CME News Author: Allison Gandey CME Author: Laurie Barclay, MD Disclosures Release Date: February 28, 2008; Valid for credit through February 28, 2009 Credits Available Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians; Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians To participate in this internet activity: (1) review the target audience, learning objectives, and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation; (4) view/print certificate View details. Learning Objectives Upon completion of this activity, participants will be able to: Describe the risk for venous thromboembolism associated with use of erythropoiesis- stimulating agents for treatment of anemia in patients with cancer. Describe the risk for mortality associated with use of erythropoiesis-stimulating agents for treatment of anemia in patients with cancer. Authors and Disclosures Allison Gandey Disclosure: Allison Gandey has disclosed no relevant financial relationships. Stem Cell Protein Stops Cancer in its Tracks (Ivanhoe Newswire) -- A protein found in human embryonic stem cells is showing promise in fending off the spread of deadly cancers. Researchers say the protein, which they’ve dubbed “Lefty,” inhibits the production of another protein known as Nodal, found in embryonic stem cells and cancer cells alike. Under normal circumstances, Nodal plays a key role in helping embryonic stem cells turn into the different cells needed in the human body, such as tissue cells, skin cells, etc. In this study, cells found in melanoma (skin cancer) and breast cancer were found to over- produce Nodal, thus leading to the spread of the cancers. But when the researchers exposed the cells to Lefty, the over-production of Nodal came to a halt. Tumors began to decrease, and an increase was seen in the programmed suicide of the cancer cells. “The remarkable similarity of the responses of the two tumor types is likely attributable to the commonality of plasticity . . . that indiscriminately unifies highly aggressive cancer cells, regardless of their tissue of origin,” study author Mary J. C. Hendrix, M.D., from Northwestern University, was quoted as saying. She says she believes the tumor suppressive qualities of Lefty identified by this study could open the door to new and better treatments for melanoma, breast cancer, and possibly other types of cancer as well. Finding better treatments for aggressive melanoma and breast cancer is vital, because both conditions carry high death rates. The median survival time for someone diagnosed with metastatic melanoma is less than 7.5 months. More than 40,000 women died from metastatic breast cancer in 2007 alone. Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here. SOURCE: The Proceedings of the National Academy of Sciences, published online March 3, 2008 Scientists Track Down Smoking-Cancer Link (Ivanhoe Newswire) -- We all know smoking causes lung cancer -- but which of the thousands of ingredients in cigarettes is at fault? Researchers from the University of California, Davis, believe they’ve found a big piece of that puzzle. In a study conducted in the laboratory, they discovered human lung airway cells exposed to either cigarette smoke or hydrogen peroxide -- one of several oxidants found in cigarettes -- both developed changes indicative of cancer. Airway cells not exposed to either cigarette smoke or hydrogen peroxide did not undergo the changes. Study authors say identifying the specific substances in tobacco that cause lung cancer is a major step forward, both in the development of safer cigarettes and, most importantly, drugs to combat lung cancer once it develops. “With the five-year survival rate for people with lung cancer at a dismally low 15.5 percent, we hope this study will provide better insight into the identification of new therapeutic targets,” study author Tzipora Goldkorn was quoted as saying. Gerald Weissmann, M.D., editor-in-chief of the journal that published the study, echoes those sentiments. “Guns kill, bombs kill and cigarettes kill,” he was quoted as saying. “While biologists can’t do much about the first two, studies like this will help in the fight against tobacco-related death and disease.” Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here. SOURCE: The FASEB Journal, published online Feb. 28, 2008 Posted February 29, 2008Higher rate of abnormal mammograms in women on combined HT Print Email Discuss in our forum Women considering combined hormone therapy should be counseled about the risks vs. benefits due to the adverse effect the therapy has on breast cancer detection. A team of researchers from the Women’s Health Initiative conducted a trial to determine the effect of combined HT on breast cancer detection. Post-menopausal women (n=16,608) were randomly assigned to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or to receive placebo. Breast examinations, including mammography, were performed each year. Researchers evaluated mammography results for 5.6 years of treatment to determine its effects on cancer detection. The overall frequency of abnormal mammograms was higher in the HT group than in placebo (35% vs. 23%; P<.001). Breast biopsies in the HT group diagnosed cancer less frequently than in the placebo group (14.8% vs. 19.6%, P=.006), despite a greater increase in breast cancers and diagnosis at higher stages in the HT group, the researchers wrote. Those assigned to combined HT had an approximate 4% greater risk of an abnormal mammogram after one year and an approximate 11% greater risk after five years, compared with placebo. – by Stacey L. Adams Arch Intern Med. 2008;168:370-377. The researchers report ancillary findings of the WHI with an eye to understanding how conjugated equine estrogen plus medroxyprogesterone acetate for approximately five years affected the ability to diagnose breast cancer. Recall that the reason this arm of the WHI was stopped was because of greater relative risk of invasive breast cancer and a higher incidence of stage 2B or greater cancers compared to placebo. The findings are not surprising given our understanding of how estrogen and progestin in combination is associated with more breast density. Unfortunately, assessing breast density was not planned for in the WHI. The findings don't help us with estrogen-only therapy. The WHI, however, also found that there was no increase in mammograms suspicious or highly suggestive of malignancy in the active arm. Prior work suggests that these changes happen when estrogen is coupled with a progestin necessary to avoid increased endometrial cancer risk from unopposed estrogen alone. Current prescriptions most commonly use lower doses of estrogens and progestins (when the uterus is present), and alternative preparations and route of delivery are more commonplace. We have also improved our screening capability with more experience and with better technology. Currently, screening methods are being studied to determine how best to deal with breast density given that it is more common in younger patients and those in need of hormone treatment when the risk-benefit suggests it is needed. Many physicians avoid mammography in patients with dense breasts and use alternative screening methods. Optimum strategies are yet to be understood. The delivery and the methodology are improving all the time. I have consistently discussed the problem of more dense breasts leading to more difficulty with diagnosis. These findings don't change that discussion. The quantitative risk can't be transferred precisely to current risk-benefit discussions. On the other hand, it is nice to see that it has been quantified for this dose. It is one more bit of information that helps us inform our patients better. It is unfortunate that only one preparation and one dose of estrogen and progestin were used in the WHI randomized controlled trial. – Robert A. Wild, MD, PhD, MPH Professor of Reproductive Endocrinology Oklahoma University Health Sciences Center, Oklahoma City NCCN task force findings raise questions on future oral chemotherapy use Malignancies increased in women after stopping hormone therapy HER2 status may predict response to adjuvant anthracycline therapy Laurie Barclay, MD Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships. Brande Nicole Martin Disclosure: Brande Nicole Martin has disclosed no relevant financial information. February 28, 2008 — Erythropoietin and darbepoetin, often used to treat chemotherapy- associated anemia in patients with cancer, might cause serious complications such as venous thromboembolism (VTE) or even death. Although previous systematic overviews of trials have identified the risk for VTE related to the drugs, this new meta-analysis, published in the February 27 issue of the Journal of the American Medical Association, is the first to identify mortality. Speaking to Medscape Oncology, lead author Charles Bennett, MD, PhD, from the Veterans Administration Chicago Healthcare System at the Northwestern University Feinberg School of Medicine in Chicago, Illinois, said he was surprised by the finding. "With 15 years of data, we are the first to detect a mortality risk with these agents." Dr. Bennett said this study highlights the need for academic pharmacovigilance outside of industry or a regulatory setting. "We really need to question the safety of pharmaceuticals and the diligence with which they are being studied," he said. Many questions remain for doctors and patients using erythropoietin and darbepoetin. Dr. Bennett advocates using the drugs with caution at this time. "We found a 1.57-fold increased venous thromboembolism risk and a 1.10-fold increased mortality risk when erythropoiesis- stimulating agents [ESAs] were administered to patients with anemia and cancer," the authors write. "These risks are important given the prevalence of erythropoiesis-stimulating agents use as supportive care drugs among patients with cancer," they add. The US Food and Drug Administration (FDA) indicated that it will hold a meeting of its Oncologic Drug Advisory Committee (ODAC) next month to review safety concerns. "I hope this study and others will encourage more energy at the next ODAC meeting in March," Dr. Bennett said during an interview. Drugs Boost Risk for VTE and Death At a December 2007 workshop on ESAs and tumor growth, convened by the National Cancer Institute, clinical and basic-science researchers agreed that continued preclinical work is necessary to evaluate the precise role of erythropoietin and erythropoietin-receptor expression in human cancers. Researchers attending the workshop said that future clinical trials should include the collection of tissue specimens to directly assess the drugs' effects on tumor cells. Although the mechanism by which the agents affect the survival of patients with cancer is not completely understood, there is concern about the potential for the products to directly affect tumors. The drugs received approval from the FDA for cancer indications in 1993 and 2002 based on transfusion benefits among patients with nonmyeloid malignant tumors who developed anemia associated with chemotherapy. When erythropoietin received its approval, issues pertaining to VTE and tumor progression were raised. Early trials evaluated serum hemoglobin levels and red blood cell transfusions when ESAs were administered to patients to treat chemotherapy- associated anemia. According to the authors, 2 trials reported in 2003 evaluated the potential for the drugs to improve overall or progression-free survival. In these trials, poorer survival was identified for patients with breast cancer who were treated with ESAs and chemotherapy and for patients with head and neck cancer who received radiotherapy. Agents Might Also Directly Affect Tumors In the current analysis, researchers collected data from a variety of sources, including a published overview from the Cochrane Collaboration, MEDLINE, and Excerpta Medica databases. They also used the FDA's public Web site, drug manufacturers, and safety advisories. Investigators included phase 3 trials comparing ESAs with placebo or standard of care for the treatment of anemia among patients with cancer. The group extracted mortality and VTE rates and 95% confidence intervals (CIs) from 51 clinical trials with more than 13,000 patients. Another 38 clinical trials with more than 8100 patients provided additional information on VTE. The researchers point to a number of study limitations. For example, they did not have access to original source data and therefore evaluated trial summaries reported in overviews, published literature, and FDA briefing materials. They pooled results of individual trials, most of which had limited ability to evaluate survival or tumor progression. Also, they note that the definitions of VTE varied across trials, and the rate of this complication was not a predefined primary- outcome measure in any trial. The group did not report separately on erythropoietin and darbepoetin. The researchers say this is because American Society of Clinical Oncology/American Society of Hematology guidelines, the National Comprehensive Cancer Network guidelines, and the FDA consider the products to belong to a single class. The investigators conclude: "Our findings, in conjunction with basic-science reports on erythropoietin and erythropoietin receptors in solid cancers, raise concern about erythropoiesis- stimulating agents' safety for patients with cancer." They add that additional research is clearly needed. Dr. Charles Bennett has disclosed receiving previous grant support from Amgen. Both Dr. Bennett and coauthor Benjamin Djulbegovic, MD, PhD, professor of medicine and oncology at the H Lee Moffitt Cancer Center and Research Institute at the University of South Florida in Tampa, have disclosed serving as consultants to Amgen. Coauthor Anthony Blau, MD, from the department of medicine/hematology and the Institute for Stem Cell and Regenerative Medicine at the University of Washington in Seattle, has disclosed being named as an inventor on patent applications related to the regulation of blood cell production. Dr. Blau is also a cofounder of CellNexus LLC, which aims to develop this technology for the treatment of anemia. Coauthor Samuel Silver, MD, PhD, from the University of Michigan Health System in Ann Arbor, has disclosed being a consultant for Bear Stearns, Maverick Capital, and the Marwood Group. JAMA. 2008;299:914-924. Clinical Context Erythropoietin and darbepoetin, both FDA-approved ESAs, are widely used to treat anemia in patients with cancer. Early concerns regarding use of erythropoietin included possibly increased risk for VTE and tumor progression. In 2003, research studies showed poorer survival for patients with breast cancer who were treated with ESA and chemotherapy. The FDA is planning a meeting of its ODAC in March 2008 to review safety concerns with ESAs. Although systematic overviews of trials have shown increased risk for VTE, none have examined mortality risks. The present review highlights findings from phase 3 trials of ESA used to treat anemia in patients with cancer. Study Highlights The goal of this review was to evaluate rates of VTE and mortality associated with ESA administration to treat anemia among patients with cancer. The investigators searched the Cochrane Collaboration from January 1, 1985, to April 1, 2005, and MEDLINE and EMBASE databases, the public Web site of the FDA, ESA manufacturers, and safety advisories from April 1, 2005, to January 17, 2008. Key words used for the search were "clinical trial," "erythropoietin," "darbepoetin," and "oncology." The review included both independent and industry-sponsored studies. These sources were supplemented by reports for phase 3 trials reported more recently, enrolling a total of 4062 patients. All 8 of these trials prospectively evaluated survival as a primary or secondary outcome, and they individually identified increased rates of tumor progression or mortality associated with ESA use. Inclusion criteria for identified studies were phase 3 trials comparing ESAs with placebo or with standard of care to treat anemia in patients with cancer. 3 reviewers extracted mortality rates, VTE rates, and 95% CIs from evaluated trial summaries reported in overviews, published literature, and FDA briefing materials. Included studies were 51 clinical trials with a total of 13,611 patients that included survival information and 38 clinical trials with a total of 8172 patients that included information on VTE. For the mortality analysis, a median of 223 patients were included in the individual trials. 40 trials with 8878 patients evaluated epoetin alfa or epoetin beta, and 11 trials with 4733 patients evaluated darbepoetin. Duration of ESA treatment ranged from 6 to 52 weeks; follow-up duration ranged from 11 to 62 months. Patients with cancer who were treated with ESAs had increased risks for VTE (334 VTE events among 4610 patients treated with ESA vs 173 VTE events among 3562 control patients; 7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31 - 1.87). The association of ESA use with VTE risk was not dominated by a small number of trials. Patients with cancer who were treated with ESAs also had an increased risk for mortality (hazard ratio [HR], 1.10; 95% CI, 1.01 - 1.20). Subgroup analysis showed that patients in the ESA group had increased mortality risks in the anemia of cancer studies (HR, 1.29; 95% CI, 1.00 - 1.67; P = .05) and a increase in mortality risk in the treatment-related anemia studies (HR, 1.09; 95% CI, 0.99 - 1.19), both of which were nonsignificant results. The association of ESA use with mortality was also not dominated by a small number of trials. Based on these findings, the authors concluded that administering ESA to patients with cancer is associated with increased risks for VTE and mortality. With respect to basic science studies on erythropoietin and erythropoietin receptors in solid cancers, these findings also raise concern about the safety of ESA administration to patients with cancer. The investigators suggest that these safety concerns may account, in large part, for changes observed in patterns of use, reimbursement policies, clinical guidelines, and FDA-approved package inserts regarding oncologic use of ESAs. Limitations of this analysis are lack of access to original source data, varying VTE definitions across trials, VTE rate not a predefined primary outcome measure in any trial, and failure to report separately on epoetin vs darbepoetin. Pearls for Practice Administration of ESAs to patients with cancer is associated with increased risks for VTE. The association of ESA use with the risk for VTE was not dominated by a small number of trials. Administration of ESAs to patients with cancer is associated with increased mortality, with findings similar in patients with anemia of cancer and in those with treatment-related anemia. These findings, in conjunction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer. Reported March 24, 2008 Destroying Thyroid Cancer LOS ANGELES (Ivanhoe Newswire) -- Every year in the United States, more than 33,000 people will develop thyroid cancer. It's a slow-growing disease and is one of the least-deadly cancers, but when it reaches an advanced stage and starts spreading to other organs, that prognosis changes. And treatment options are limited. Now, a new drug is extending -- even saving -- lives. You'd never know it, but Connie Smith has had thyroid cancer for a third of her life. "I was diagnosed when I was 40, 21 years ago," Smith says. She's had two surgeries and a lifetime of radioactive iodine to keep the slow-growing cancer in check. But a few years ago, it spread to her lungs. "It just looked like you took a paintbrush, dipped it into ink and then splattered it on a white wall. It was all through my lungs, so it's inoperable," Smith says. Dr. Lee Rosen offered Smith a new drug -- Axitinib -- in a class of drugs called VEG-F inhibitors. They cut off blood supply to tumors and are thought to block several receptors on cancer cells. "We don't really know why exactly they work, but as long as they work, I always say that we'll figure it out later," says Lee Rosen, M.D., a hematologist and oncologist with Premiere Oncology in Santa Monica, Calif. One study shows 30 percent of patients with advanced thyroid cancer had tumors shrink by more than half. Another 40 percent saw their cancer stop growing. "Our longest patients have been on this study for three, three and a half years already -- [that's] completely unheard of," Dr. Rosen says. Smith started the drug three years ago -- hoping it would save her life. "When she started the study, her prognosis was probably that she had a 20 to 30 percent chance of being alive in a year," Dr. Rosen says. Now, the tumors in her lungs are all but gone. "What can you say when someone gives you time? It's just wonderful," Smith says. Dr. Rosen says there are several trials going on across the country studying this class of drugs for many different types of cancer. Side effects of the drugs can include fatigue and sores in the mouth, and on the hands and feet. FOR MORE INFORMATION, PLEASE CONTACT: Premiere Oncology http://www.premiereoncology.com (310) 633-8400 _______________________________________________________________________ _________________ Reported March 28, 2008 Early Detection of Oral Cancer SAN FRANCISCO, Calif. (Ivanhoe Newswire) -- Each year, more than 34,000 Americans are diagnosed with oral cancer. The best chance at survival is early detection. Now, a new device can catch oral cancer earlier than ever before. Dentist Stephen Brattesani is on a mission -- to find oral cancer early and destroy it. "In a 24-hour period, every hour, one person dies of oral cancer. If we can be preventative ... saving a life ... that's what it's all about," says Stephen Brattesani, D.D.S., a dentist with Marina Pacific Heights Dental Care in San Francisco, Calif. A new device -- called VELscope -- is doing that. It uses a non-invasive blue light to spot oral cancer in its earliest stages. "Anything that's healthy shows up appleish green. Anything that's not healthy shows up in a dark color so cancer or basal cells that started to change would show up like an oil slick," Dr. Brattesani says. Until now, oral cancer was only detected once it hit surface tissue. With this light, abnormalities are found far below the surface -- even in pre-cancerous states. "It's the closest thing we have to the earliest detection process available," Dr. Brattesani says. The light found a suspicious dark spot in Spencer Larson's mouth. A biopsy followed -- it's not cancer -- a relief to Larson. "It shows a cleaning is more than a cleaning. It's a check-up," Larson says. Katherine Brienze says the new test is extra protection. "I'm really glad that it's so easy. It's not invasive and it doesn't hurt ... and it takes seconds," Brienze says. "It allows the dentist to screen patients and be proactive in having a way of stopping the disease process that unfortunately all too often has been a death sentence," Dr. Brattesani says. When oral cancer is caught early, 90 percent of cases are curable -- providing a blue light at the end of the tunnel. In the last thirty years, there has been a 60 percent increase in oral cancer in adults under age 40. If it's not caught in an early stage, more than half of people diagnosed with it won't live five years. VELscope is FDA approved and available to dentists right now. FOR MORE INFORMATION, PLEASE CONTACT: Steven Brattesani, DDS http://www.drbrattesani.com VELscope Web site www.velscope.com/ Oral Cancer Foundation www.oralcancerfoundation.org/ Reported March 26, 2008 Gastric Bypass Alternative SAN FRANCISCO, Calif. (Ivanhoe Newswire) -- More than 177,000 Americans had weight loss surgery in 2006. This can mean massive weight loss, but the surgery doesn't come without risks. Now, an investigational approach is helping patients shed pounds a whole lot safer. Losing weight was never easy for Garth Michaels. "I've felt fat all my life, really," Michaels says. He topped out at 320 pounds. "I really was just up against a wall. I was praying daily. I didn't know where to turn," Michaels says Then, he found Dr. Robert Lustig. "Everyone in the world seems to think that obesity is one problem, you know, you eat too much, exercise too little and it couldn't be further from the truth," says Robert Lustig, M.D., an endocrinologist at the University of California, San Francisco. Dr. Lustig says the vagus nerve, which tells the brain when the body's full, plays a big part in obesity. "Every single thing the vagus nerve does is designed to get energy into your fat cells," Dr. Lustig says. He's testing an easy-on-the patient surgery called a laparoscopic vagotomy where he actually cuts the vagus nerve. "The severe hunger that many obese patients report seems to be just completely obviated - it goes away completely," Dr. Lustig says. An early study shows the 20 minute procedure led to an average 18 percent excess weight lost. "The weight loss that the patients have achieved appears to be durable and we're very happy about that," Dr. Lustig says. Michaels has lost more than 100 pounds since having the procedure nearly two years ago. "Definitely life-saving. I think I added at least 10 to 20 years to my life," Michaels says. "It's a whole new life -- a whole new lease on life and at age 56, that's pretty good." And after a lifetime of big clothes, Michaels is proud to finally shed that image. Not only does the procedure have fewer side effects than gastric bypass, but it's cheaper, too! Bypass surgery costs between $25,000 and $50,000, while this new procedure would cost between $5,000 and $10,000. The procedure does not cause the massive weight loss patients report after gastric bypass, but Dr. Lustig says it typically does cause more weight loss than weight-loss drugs. This technique is still being studied and not yet widely available. FOR MORE INFORMATION, PLEASE CONTACT: Phyllis Brown University of California, San Francisco Public Relations phyllis.brown@ucsf.edu Reported March 27, 2008 Patient Navigators LOS ANGELES, Calif. (Ivanhoe Newswire) -- Cancer kills one in four people in the United States, but research shows it's not an equal opportunity killer. Lower income and lack of health coverage contribute to worse outcomes. But change is coming. When Bill Rivera was diagnosed with colon cancer four years ago, he was floored. "It was tough. Very, very tough," Rivera says. Even tougher was getting to all the appointments. "See the cardiologists, see the gastroenterologist, see the oncologist," Rivera says. Luckily, he had help from a patient navigator. "Patient navigators are basically like shepherds, to sort of guide patients through cancer treatment," says David Khan, M.D., a radiation oncologist with Cancer Care Consultants in Los Angeles, Calif. Dr. Khan says navigators help low-income patients who often don't have resources to get the treatment they need. "Transportation is the very biggest barrier to treatment." Dr. Kahn says. In a recent study, navigators reduced the time it took to overcome barriers like that from 42 days to one; and two-thirds of patients said navigators greatly improved their care. "It's purely free of charge. It's optional if patients want to receive navigation services." Cancer survivor Lillian Morton-Benbow was Rivera's navigator. For 40 patients, she's done everything from lend an ear to transport them to appointments. "If they need to have a fight for social security, I'll go and fight with them," Morton-Benbow says. She fought to get Rivera disability insurance, found him financial aid … and became a friend. "I'm enjoying now. If it wasn't for the program, who knows what's going to happen?" Rivera says. Today, he's in remission and instead of doctor's appointments … he's got grandson appointments. The National Cancer Institute provides funding for patient navigator programs across the country in underserved populations. Some programs have paid social workers that serve as navigators. Others like Morton-Benbow are volunteers. Doctors and patients are already seeing dramatic effects. In Harlem, at one hospital alone, the five-year survival rates from breast cancer have risen dramatically since patient navigators came on the scene. Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here. FOR MORE INFORMATION, PLEASE CONTACT: Keith Andre, Program Director Cancer Care Consultants Los Angeles, CA (310) 251-3302 Treating lymphocytic predominant Hodgkin’s disease by Wajeeha Razaq, MD An 80-year-old man with a prior history of coronary artery disease, hypertension and repaired abdominal aortic aneurysm was found to have a 2-cm retroperitoneal lymphadenopathy on a follow-up ultrasound for the abdominal aortic aneurysm. The patient denied any symptoms including fevers, night sweats or weight loss. Wajeeha Razaq On examination, he had left axillary lymphadenopathy, but no cervical, supraclavicular or inguinal lymphadenopathy was noticed. The liver and spleen also were not palpable. He underwent left axillary lymph node biopsy, which was consistent with lymphocytic predominant Hodgkin’s disease. Classical lymphocytic and histiocytic cells were found. The immunohistochemistry revealed CD20+, focal CD45+, CD15– and CD30– cells, confirming the diagnosis of lymphocytic predominant Hodgkin’s disease (See image). A subsequent positron emission tomography/computed tomography scan revealed bilateral axillary, mesenteric and pelvic lymphadenopathy. His complete blood count was normal. A bone marrow biopsy was not performed. He had an excellent performance status and continued to work full time as an accountant. A lymphocytic and histiocytic cell (“popcorn cell”) is a hallmark for lymphocytic predominant Hodgkin’s disease. Source: W Razaq What will you do next? A) Treat with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) B) Treat with rituxan, cytoxan, vincristine and prednisone C) Treat with rituxan weekly for four weeks D) Watchful waiting CASE DISCUSSION Hodgkin’s disease includes two different disease entities: the rare lymphocytic predominant Hodgkin’s disease accounting for <5% of cases, and classical Hodgkin’s disease comprising 95% of all cases. In the World Health Organization classification as well as in the recently proposed InterLymph classification system, lymphocytic predominant Hodgkin’s disease still comes under the general category of Hodgkin’s disease but is separated from the classical Hodgkin’s disease based on morphologic and immunophenotypic features. Morphologically, lymphocytic predominant Hodgkin’s disease is distinguished from classical Hodgkin’s disease by the presence of an atypical Reed-Sternberg cell called a lymphocytic and histiocytic cell, also known as “popcorn cell,” as its nucleus resembles an exploded popcorn kernel. These cells have vesicular and hyperlobulated nuclei, with small but distinct nucleoli. Immunophenotypically, the classical Reed-Sternberg cells stain positive for CD15 and CD30 but lack the B cell marker CD20. In contrast, the lymphocytic and histiocytic cells are positive for the leukocyte common antigen (CD45) and express B cell antigens (eg, CD19, CD20, CD22) but lack CD15 and rarely express CD30. Clinically, lymphocytic predominant Hodgkin’s disease usually presents as asymptomatic peripheral lymphadenopathy. The clinical course of this disease is different from classical Hodgkin’s disease as it progresses slowly but with frequent relapses after the treatment, which are rarely fatal. The indolent nature and favorable prognosis of the disease is illustrated by many published reports of patients with early stage disease who enjoyed excellent overall survival without any treatment (93% at five years and 80% at 10 years). Although there are no randomized data to support watchful waiting in stage IIIA lymphocytic predominant Hodgkin’s disease, given the advanced age of the patient, we elected to watch him carefully to avoid treatment-associated toxicities. A follow-up was performed every three months, and a PET/CT scan was performed every four to six months. He remained stable for one year. Eventually, a PET scan showed new hypermetabolic lesions involving his spleen along with previously reported lymphadenopathy. There are limited data concerning the choice of chemotherapy regimens when used initially or at relapse. Regimens used in classical Hodgkin’s disease, eg, ABVD, mechlorethamine, vincristine, procarbazine and prednisone (MOPP) or MOPP-like regimens have been tried with durable complete remission. In one published report, 10-year overall survival for patients with advanced stage lymphocytic predominant Hodgkin’s disease treated with radiation alone or with chemotherapy and radiation was reported to be 93%, with increased toxicity in the combined therapy arm. Nearly all deaths were cardiac or second malignancy related. This suggests that less aggressive treatment for lymphocytic predominant Hodgkin’s disease might continue to yield good results while perhaps lowering the long-term risk for complications. Rituximab, a monoclonal antibody against CD20, has been tried successfully in various B cell hematological malignancies, and recently there has been increasing interest in exploring its role in lymphocytic predominant Hodgkin’s disease as the neoplastic cells express CD20. Data from two phase-2 trials indicated high response and remission rates in untreated and previously treated patients. We treated our patient with a standard dose of rituximab weekly for four weeks. He tolerated the treatment well and continued to work full time. A repeat PET/CT scan showed complete resolution of splenic lesions and partial resolution of hypermetabolism associated with axillary and iliac lymph nodes. In summary, treatment remains controversial; however, recent understanding of the molecular pathogenesis of lymphocytic predominant Hodgkin’s disease could lead to modification of current therapeutic approach to this disease. Wajeeha Razaq is a third-year HemOnc Fellow at St. Luke’s Roosevelt Hospital Center in New York and is a member of the HemOnc Today Editorial Board. For more information: Bodis S, Kraus MD, Pinkus G, et al. Clinical presentation and outcome in lymphocyte- predominant Hodgkin’s disease. J Clin Oncol. 1997;15:3060-3066. -------------------------------------------------------------------------------------- Too Few Cancer Survivors Pursue Healthy Lifestyles By Amanda Gardner HealthDay Reporter Wed Apr 30, 7:01 PM ET WEDNESDAY, April 30 (HealthDay News) -- Cancer survivors who eat more fruits and vegetables, stay physically active and avoid tobacco have a higher quality of life than those who don't do these things. The bad news is that many cancer survivors aren't eating right and aren't exercising enough, although a good three-quarters do follow recommendations not to light up. "We all know that living a healthy lifestyle, eating well, being physically active and not smoking reduces the risk of physical problems and improves overall physical health," said Kevin Stein, director of Quality of Life Research at the American Cancer Society's Behavioral Research Center. "Here we have additional evidence that it not only reduces disease burden but also improves emotional health and quality of life and, moreover, the effect appears to be cumulative. The more you comply, the better your quality of life." Stein is senior author of a new study detailing the findings, published in the May issue of the Journal of Clinical Oncology. Yet the message doesn't seem to be getting through. "When I sit down and talk to patients about changing their lifestyle after treating them for cancer, a lot of times you're glaring into people's eyes, and they don't really believe what you're telling them," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "I don't think really people really grasp the importance of what they do in their lives in terms of how it affects what happens to them." That would include behaviors engaged in both before and after a cancer diagnosis and treatment. More than 10 million Americans are cancer survivors, making them more vulnerable to other health conditions such as heart disease, osteoporosis, diabetes and, more generally, a reduced health-related quality of life. The American Cancer Society recommends that cancer survivors engage in 30 minutes of exercise at least five times a week, eat at least five servings of fruits and vegetables a day, and not smoke. Previous studies have shown that a healthy lifestyle can prevent cancer recurrence and prolong survival, yet many of these studies were conducted at elite cancer treatment centers, Stein said. The new study aimed to get a more realistic portrayal of the issue by asking more than 9,000 survivors about their quality of life. Participants were either two-, five- or 10-year survivors of six different types of cancer. Only 14.8 percent to 19.1 percent of survivors were meeting the five-a-day fruits and vegetables recommendation, while 29.6 percent to 47.3 percent were meeting the physical activity recommendation. On the other hand, 82.6 percent to 91.6 percent didn't smoke. But a mere 5 percent were meeting all three recommendations, up to 12.5 percent weren't complying with any lifestyle behavior recommendations, and less than 10 percent were meeting two or more. The findings echoed a recent study that found that cancer survivors have rates of obesity and physical inactivity similar to those of the general population. That study, published in the June 1 issue of Cancer, found that less than one-quarter of cancer survivors were regularly physically active, and more than 18 percent were obese. "We want to focus on survivors because of their increased risk" for other conditions as well as cancer recurrence, Stein said. "In addition, they're in the health-care system, so this is a teachable moment," he added. "We have an opportunity to talk to them about their health, communicate to them, 'Hey, you've dodged a bullet this time, here's an opportunity for you to live a healthy lifestyle and reduce the risk of a second cancer or another co-morbid condition and also improving your quality of life.' " More information The American Cancer Society has more on cancer risk and lifestyle factors. http://news.yahoo.com/s/hsn/20080430/hl_hsn/toofewcancersurvivorspursuehealthylifestyles ----------------------------------------------------------------------------------------------- - Lip Balms and Glosses May Boost Skin Cancer Risks Sat Apr 26, 11:45 PM ET SATURDAY, April 26 (HealthDay News) -- Shiny lip balms and glosses may attract ultraviolet rays and increase the risk of skin cancer, warns a dermatologist at Baylor University Medical Center at Dallas. ADVERTISEMENT Dr. Christine Brown noted that protecting your lips from harmful sun rays is as important as using sunscreen to protect your skin. But a recent study found that less than 25 percent of Americans use some form of lip protection. Lips are more susceptible than skin to aging from chronic sun damage and also more prone to developing serious cancers. "When skin cancer occurs on the lower lip, it has the potential to be much more aggressive and metastasize to surrounding lymph nodes," Brown said in a prepared statement. Shiny balms and glosses don't offer protection. Instead, they attract the sun's rays to the lips. "What most people don't realize is they're actually increasing light penetration through the lip surface by applying something clear and shiny to them," Brown said. Women should only wear glossy lipsticks in the sun when they have a layer of sun protection on underneath, dermatologists advise. Anyone who's planning on being outdoors for more than 20 minutes at a time should use a lip sun block with an SPF of 30. Women should apply it in the morning under any lipsticks or lip glosses and then reapply the sun block throughout the day. People should check their lips for signs of cancer. Consult a dermatologist if you notice any changes to the color of the lip surface (an area turns opaque or white), or if you have persistent peeling or flaking of a spot on your lip, Brown said. More information The U.S. National Cancer Institute has more about lip and oral cancer. http://news.yahoo.com/s/hsn/20080427/hl_hsn/lipbalmsandglossesmayboostskincancerrisks --------------------------------------------------------------------------------------------- Experimental Cancer Vaccines Show Promise By Amanda Gardner HealthDay Reporter Tue Apr 15, 7:02 PM ET TUESDAY, April 15 (HealthDay News) -- A germ that commonly causes food poisoning may be the next weapon in the fight against cervical cancer, a major cause of death among women worldwide. ADVERTISEMENT A new trial shows that a live Listeria vaccine called Lovaxin C is safe and even showed some benefit in 15 women with advanced cervical cancer. Listeria is a common bacteria found on leafy vegetables and dairy products. "Most of us eat it routinely but don't know it, because it generates a strong immune reaction," study lead author John Rothman, vice president of clinical development at Advaxis Inc. of North Brunswick, N. J., which makes the vaccine, said at a Tuesday news conference. "It can cause disease, but it's safe, because the lowest doses of any number of antibiotics will clear it and will do it without impeding the immune response." This vigorous immune response is what researchers are hoping will give the vaccine a fighting chance against cervical cancer. According to Rothman, there are at least 10 ways that Listeria attacks tumors, and probably more. Most of the women involved in this study had stage 4 disease and had failed prior surgery, chemotherapy or radiation. All women were given the vaccine as well as the antibiotic ampicillin. By study's end, only five patients still had progressive disease, seven were stable and one demonstrated a partial response to the vaccine. Three of the seven stable patients showed tumor reductions of about 20 percent and one of more than 30 percent. The vaccine did cause flu-like symptoms in all patients (fever, chills, nausea), but those who had received lower-dose vaccines were treated easily with over-the-counter drugs, the researchers said. Rothman's study was just one of several showing promise that were presented Tuesday at the American Association for Cancer Research annual meeting, in San Diego. A second study, out of the Netherlands, found that the GVAX vaccine stimulated a significant immune response in men with prostate cancer. Five out of six participants receiving the highest dose of vaccine showed declines in PSA (prostate-specific antigen) levels of 50 percent or more. "This appears to be a promising approach," study lead author Saskia Santegoets of VU University Medical Center in Amsterdam, said at the news conference. Another vaccine -- this one for prostate cancer that hasn't responded to other therapies -- also showed hope. Three of six patients who received the highest dose of the vaccine saw declines in PSA levels of more than 50 percent. The trial involved 24 patients overall. According to lead author Dr. Lawrence Fong of the University of California, San Francisco, the vaccine works by "educating" the immune system." And, finally, antibody directed enzyme pro-drug therapy (ADEPT) showed positive responses in 44 percent of patients with either colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, pancreas or cancer of unknown primary site. With ADEPT, an enzyme activates a drug that has been targeted to the tumor by an antibody, at the site of the tumor. More information The U.S. National Cancer Institute has more on cancer vaccines. http://news.yahoo.com/s/hsn/20080415/hl_hsn/experimentalcancervaccinesshowpromise -------------------------------------------------------------------------------------- Treatment Lessens Side Effects By Ben Hogwood It is estimated more than 200,000 men in the United States will be diagnosed this year with prostate cancer. Now, patients diagnosed in the metropolitan area can benefit from a new piece of equipment that limits the damaging side effects of radiation treatment. The equipment is called the Calypso 4D Localization System and it is nicknamed “GPS for the Body.” And the only hospital that has it locally is Long Island Jewish at North Shore University Hospital. “This represents a paradigm change in our ability to deliver high doses of radiation in a safer environment,” said Dr. Louis Potters, radiation oncologist at the hospital. Of the men diagnosed with this type of cancer, Dr. Potters said 175,000 of those are treatable. There are three types of treatment: surgery, radiation and seed implantation. Calypso is an add- on for patients receiving beam radiation. Its purpose is not to increase the success rate of the treatment, but to reduce the radiation’s side effects. “The concept of external radiation is almost like spotlight beams aimed at the tumor,” said Dr. Potters. Over the last 15 years, technology has been enhanced to more accurately target the cancer cells, which in turn have resulted in a higher success rate. The problem with radiation treatment is that the prostate can move – via the patient coughing or yawning or a change in volume of the bladder – and healthy tissue can be affected. “When you deal with radiation beams, a millimeter shift in the prostate may be meaningful,” said Dr. Potters. But the Calypso systems allows doctors to tell when the prostate shifts, allowing them to stop treatment if necessary to realign the patient’s body. This is done by permanently inserting three beacons no larger than the size of a grain of rice in the prostate. It’s a simple, 10-minute procedure, Dr. Potters said. Then, when the radiation treatment is given, doctors can track the location of the prostate, much like a GPS system tracks the location of a vehicle. “The patients on a day-to-day basis don’t feel any different,” he said. “There is no difference in treatment, but long-term, the accuracy of treatment will be translated into fewer side effects,” such as incontinence, impotence, sterility and lymphedema. The technology has been in some clinics for over a year now, and Dr. Potters said those locations are starting to confirm fewer complications. Dr. Potters said he has been treating prostate cancer now for 17 years and he finds it amazing at how much the prostate actually moves during the course of treatment. He was initially cynical of this technology, but now believes it will prove beneficial over time and may evolve into becoming a standard of care. “The hospital has a history of pioneering a lot of technological advances that are now commonplace,” he said. “This is just another in a long line of technologies where North Shore LIJ is ahead of the pack.” http://www.queenstribune.com/news/1210872542.html ------------------------------------------------------------------------------------------- Bringing 'Strength for Life' to cancer patients Free exercise classes may alleviate anxiety, back pain, depression and fatigue By Linda Benninghoff May 15, 2008 | 02:33 PM Who knew that even the slightest exercise, like small compressions on a mini-trampoline, could be beneficial for cancer patients? But that's exactly what Jacqui Errico and Debbie Hughes, founders of Strength for Life, have found. "It helps the gravitational force in your body and it's really supposed to help with lymphedema, which is a major problem for a lot of women with breast cancer because they've had lymph nodes removed," said Errico, who with Hughes offers trampoline activities as part of Strength for Life's free exercise classes to cancer patients. The organization's first class started eight weeks ago and the facilitators said they are willing to hold classes in almost anywhere in the Nassau-Suffolk area. "For people with a cancer diagnosis going through treatment, it's extremely difficult to travel a distance," Hughes said. "For people in Huntington, we're trying to get a location in Huntington. We're looking at churches, libraries, hospitals — facilities like that." The two leaders have associate's degrees as fitness specialists from Suffolk Community College, awarded in 2001. They are also both certified as exercise specialists from Medical Health and Fitness. The certification is necessary to train cancer patients, said Hughes. "Cancer patients are unique because the treatment breaks down your bones and also other factors like lymphedema occur," she said. "The average trainer probably shouldn't work with someone who is in treatment, unless they have the certification or the knowledge." The organization was founded to keep alive the name and mission of Evelyn Knapp, a Bay Shore resident who died of breast cancer three years ago. "She exercised before her diagnosis and during treatments and said it was the only thing that made her feel in control. It was her mission to help others," Hughes said. Knapp, with Carol Kur, cofounded the Personal Training Institute, a Jericho-based fitness and nutrition organization with locations in Huntington Bay and elsewhere around Long Island. "She lost her battle with breast cancer but we continued," Hughes said. "It's very rewarding. We see clients coming in feeling tired, and after eight weeks they are feeling good. Treatment-related fatigue, from what we understand, is an overwhelming sense of tiredness to the point that you can't even get out of bed." The organization's goals are "to grow and to reach as many people as we can." Breast cancer is a major disease on Long Island but they want to reach out to men, too. Studies dating back to 1996 have shown that exercise has helped cancer patients, according to the two leaders of the organization. A 2001 study in Cancer magazine by Victoria Mock et al. found that women who did home- based exercise for at least 90 minutes three or more days a week reported significantly less fatigue and a higher quality of life than did the women in the study who were less active during treatment. A 2004 study done in the European Journal of Cancer Care by L. Adamsen et al. found that exercise transformed the type of fatigue felt to an exercise-induced fatigue and a feeling of physical well-being instead of a negative, flu-like induced chemotherapy fatigue. And a Journal of the American Medical Association study found that women who exercised three to five times a week had a better chance of getting over breast cancer. "They had a 50 percent greater chance of survival," Errico said. The targeted exercise of "rebounding" on the mini-trampoline also helps drain a patient's lymphatic system, Hughes said. "Radiation also damages lymph nodes," Hughes added. "If you're not draining, then you're going to get swelling, usually down extremities: arms, legs. You see people who have tripled, quadrupled the size of their legs — and this helps it." "We're breaking down exercise into easy steps. Just start from the beginning do what you can and it's very self-rewarding," Errico said. The two facilitators distinguish between exercise and physical therapy, which many cancer patients have undergone. They gave seminars to Live Love Laugh, a breast cancer group that meets at Mather Hospital in Port Jefferson. "The members were pleased with the fact that it was exercise, and they felt very good afterwards," she said. Exercise helps the posture and improves back pain. Anxiety and depression contribute to fatigue, Errico said. She added, "I think the exercise is monumental and takes them away from the moment of thinking about what's going on into a more positive vein: 'I'm helping myself, I'm feeling better about myself, I can do this, I'm in control.'" Hughes said, "Evelyn always felt like her body betrayed her and that's what a lot of people with cancer feel — like their bodies betrayed them. You don't expect to get a cancer diagnosis and, when that happens, you feel very helpless so we're giving them a little piece back, yes, you can control, and make yourself feel better." The pair also endeavor to bring in volunteers, money, places to hold classes. "We are still in our infancy and we're looking for places that are willing to let us hold free exercise classes," Errico said. "We've written to some of the fitness companies asking for donations of bands and balls because when people come to our class we want to give them a band, a ball so in this way they can do it at home," she explained. "We don't want them to have to go out and buy it. They have paid so much in co-pays for their treatments, for their medical expenses, we want this to be free. Right now we've been doing it all on our own. We want to be big enough so that we can educate others and they can help us in this cause." Their first fundraiser was held Saturday, May 3 — and they plan more. "Hopefully by August, we'll do a 5K run and in the winter a fashion show, and next year, a golf outing. So we're going to need plenty of giveaways and help. Anyone experienced in nonprofit fundraising who is willing to put their time in is welcome," Hughes said. Eileen Swieczkowski, a nurse at the Fortunato Breast Health Center at Mather Hospital and also the nurse in attendance at Live Love Laugh, said, "They're wonderful at what they do; they're very patient. I have observed them at my support group and they were very wonderful with the women, showing them exercises that they could do that would be very beneficial to their health. There are a lot of articles that do support exercise during and after treatment." Email strengthforlife@optonline.net or call 974-3346. http://www.thetimesofhuntington.com/Articles-i-2008-05-15-71919.113114 _Bringing_Strength_for_Life_to_cancer_patients.html |