| LYMPHLAND |
| APRIL 2008 BREAST CANCER |
| 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 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. |
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