| LYMPHLAND |
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| BREAST CANCER MARCH 2008 |
| 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 (http://www.umich.edu) ******************************************************************************************** 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 (http://www.arrs.org) 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.fccc.edu) ******************************************************************************************** |
| 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 Email to a friendPost a CommentPrinter-friendly 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. ADVERTISEMENT 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. |
