Let's talk about the numbers for a minute. Say about 5 percent of the people with a lumpectomy and radiation therapy ultimately end up with an in-breast local recurrence, which is 1 in 20. That means 1 in 20 ends up with a mastectomy because of a recurrence and that 19 in 20 get to avoid mastectomy. So it really comes down to a question of what matters to the individual patient.
Still, there are many patients for whom the yearly mammogram and maybe MRI and physical exam is anxiety provoking, and some of those people will elect bilateral mastectomy instead. But for most patients, preserving the breast seems to be the priority, and they're willing to put up with this small risk of local recurrence in exchange for the benefits of keeping their breast.
What is the goal of adjuvant (post-surgical) therapy?
The goal of adjuvant therapy is to kill cancer cells that might have spread beyond the breast and lymph nodes before the surgery took place. They're out and about in the body, and we don't have a way of identifying exactly where they are so we have to treat with medicines that circulate throughout the body and kill cancer cells wherever they may be.
How much does chemotherapy reduce risk of recurrence?
Chemotherapy across the board lowers the annual rate of recurrence by about 24 percent. And this adds up, depending on the absolute risk of a patient, to roughly a one-fifth to one-quarter or slightly better reduction in risk at five years. That's the average for old chemotherapy regimens like CMF (Cytoxan, methotrexate and fluorouracil). Most modern chemotherapy regimens that work better than CMF will obviously offer even greater advantage.
How is someone's personal benefit from chemotherapy assessed?Chemotherapy decision-making is really challenging for everybody involved. We first have to ask ourselves what's the benefit of chemotherapy generally. Then we have to apply that to the individual patient, which means calculating her individual risk of recurrence.
Once we get into that discussion, adjuvant chemotherapy is not generally recommended unless women will likely reduce their risk of recurrence with chemotherapy by at least 1 percent. Some people will set it even higher. Clinicians often set it at 2 or 3 percent, but patients surveyed after treatment typically set it at 1 percent.
Saturday, October 28, 2006
What's the goal of surgery for a woman who has early-stage disease
For early-stage disease, the goal of surgery is to remove all of the cancer with clear margins around it and to determine the risk of spread by looking at the status of the lymph nodes under the armpit.
In the early days of breast cancer surgery, the procedure of choice was a mastectomy. But the National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a series of randomized studies that showed that just as many women could be cured with a lumpectomy and radiation therapy as could be cured with mastectomy. Women who choose lumpectomy need the radiation because it lowers the risk of local recurrence in the breast.
Does everyone require radiation therapy after lumpectomy?There is a movement afoot to look very carefully at some subgroups of people who may not need radiation after a lumpectomy. For example, researchers are looking at women with DCIS (ductal carcinoma in situ), which is a precancer that remains confined to the ducts, so we don't call it an invasive cancer. It does not have the potential, that we know of, to spread distantly beyond the breast.
As the degree of invasiveness of the cancer goes down and as the age of the patient goes up, the risk of recurrence is lower. Hence, the potential gains from radiation may be smaller.
How do women decide between mastectomy and lumpectomy?
The choice of mastectomy vs. lumpectomy is a fairly difficult one for some people. On the one hand, the mastectomy is over with quickly. You can choose to do reconstruction right away or at a later date. On the other hand, the lumpectomy allows you to preserve the breast, but generally requires four to six weeks of postoperative radiation therapy five days a week.
Some variables are technical. For example, if there is a large cancer in a small breast and the cosmetic result of a lumpectomy will be unacceptable, doctors and patients may select mastectomy. But there can be a large cancer in a woman with a very large breast that's amenable to lumpectomy.
In addition, patients who live far from a radiation center, who have economic issues with coming for treatment every day, may elect to have a mastectomy simply so they're not having to come to the hospital for six weeks for daily treatments. So there are many factors that can influence this decision and not all of them are medical.
Do women have a lot of anxiety over local recurrence following a lumpectomy? I think there is a lot of anxiety over recurrence in the breast, although we try to counsel people that that's not the major issue. In the end, what matters is whether the cancer spreads throughout the body or not. In the rare case of a local recurrence in the preserved breast, one can treat that with mastectomy.
In the early days of breast cancer surgery, the procedure of choice was a mastectomy. But the National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a series of randomized studies that showed that just as many women could be cured with a lumpectomy and radiation therapy as could be cured with mastectomy. Women who choose lumpectomy need the radiation because it lowers the risk of local recurrence in the breast.
Does everyone require radiation therapy after lumpectomy?There is a movement afoot to look very carefully at some subgroups of people who may not need radiation after a lumpectomy. For example, researchers are looking at women with DCIS (ductal carcinoma in situ), which is a precancer that remains confined to the ducts, so we don't call it an invasive cancer. It does not have the potential, that we know of, to spread distantly beyond the breast.
As the degree of invasiveness of the cancer goes down and as the age of the patient goes up, the risk of recurrence is lower. Hence, the potential gains from radiation may be smaller.
How do women decide between mastectomy and lumpectomy?
The choice of mastectomy vs. lumpectomy is a fairly difficult one for some people. On the one hand, the mastectomy is over with quickly. You can choose to do reconstruction right away or at a later date. On the other hand, the lumpectomy allows you to preserve the breast, but generally requires four to six weeks of postoperative radiation therapy five days a week.
Some variables are technical. For example, if there is a large cancer in a small breast and the cosmetic result of a lumpectomy will be unacceptable, doctors and patients may select mastectomy. But there can be a large cancer in a woman with a very large breast that's amenable to lumpectomy.
In addition, patients who live far from a radiation center, who have economic issues with coming for treatment every day, may elect to have a mastectomy simply so they're not having to come to the hospital for six weeks for daily treatments. So there are many factors that can influence this decision and not all of them are medical.
Do women have a lot of anxiety over local recurrence following a lumpectomy? I think there is a lot of anxiety over recurrence in the breast, although we try to counsel people that that's not the major issue. In the end, what matters is whether the cancer spreads throughout the body or not. In the rare case of a local recurrence in the preserved breast, one can treat that with mastectomy.
Making Decisions in Early-stage Breast Cancer
While more than 200,000 North American women are diagnosed with breast cancer every year, most of the time the disease is found in its early, most curable stages. This bodes well for the long-term survival of these women, but there are often many treatment decisions to make in a relative short and stressful span of time. Once the benefits of a particular treatment for a particular patient are assessed, women and their medical teams must weigh the risks and benefits in order to design the best treatment plan.
Tools for better decision-making are now in the works. A study published the July 28th issue of the Journal of the American Medical Association evaluated a decision aid, called a decision board, which includes pictures and text, that physicians can use when presenting information about surgery, which is one of the first breast cancer treatment decisions. Researchers found that the decision board helped patients make a more informed choice when deciding whether to have a mastectomy or a lumpectomy; the women were also more satisfied with their decision six and 12 months later.
Below, Clifford Hudis, MD, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City, talks about the goals of breast cancer therapy and how treatment decisions are best approached.
What is the goal of treatment for early-stage breast cancer?
The goal of therapy for early-stage breast cancer is cure, and there are many ways to get there. Different treatment choices will often be associated with different side effect profiles, and that's where we have to have a long discussion weighing the risks and benefits of different approaches.
For early-stage breast cancer, most people will say they're willing to put up with fairly substantial side effects in the short run because their hope is that they will never hear from the cancer again. If we're going to think of a scale, it will be tipped towards more toxicity for more benefit. When we're treating advanced cancer, however, the scale may be tipped the other way. People may not want to deal with a whole lot of toxicity or give up quality of life for very marginal benefits. So these are the kinds of decisions that come into play.
Tools for better decision-making are now in the works. A study published the July 28th issue of the Journal of the American Medical Association evaluated a decision aid, called a decision board, which includes pictures and text, that physicians can use when presenting information about surgery, which is one of the first breast cancer treatment decisions. Researchers found that the decision board helped patients make a more informed choice when deciding whether to have a mastectomy or a lumpectomy; the women were also more satisfied with their decision six and 12 months later.
Below, Clifford Hudis, MD, chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center in New York City, talks about the goals of breast cancer therapy and how treatment decisions are best approached.
What is the goal of treatment for early-stage breast cancer?
The goal of therapy for early-stage breast cancer is cure, and there are many ways to get there. Different treatment choices will often be associated with different side effect profiles, and that's where we have to have a long discussion weighing the risks and benefits of different approaches.
For early-stage breast cancer, most people will say they're willing to put up with fairly substantial side effects in the short run because their hope is that they will never hear from the cancer again. If we're going to think of a scale, it will be tipped towards more toxicity for more benefit. When we're treating advanced cancer, however, the scale may be tipped the other way. People may not want to deal with a whole lot of toxicity or give up quality of life for very marginal benefits. So these are the kinds of decisions that come into play.
Role Reversal: Chemo Before Surgery for Breast Cancer
When it comes to breast cancer treatment, there is usually a standard sequence of events. First a woman has surgery to remove the tumor, then, if necessary, she has chemotherapy to kill any remaining cancer cells in the body. But the results of a number of studies suggest reversing the order of treatment, giving chemotherapy before surgery in order to offer certain women with early-stage breast cancer an added benefit; this approach is called neoadjuvant therapy.
"Neoadjuvant chemotherapy refers to giving chemotherapy upfront before we do surgery."
says Harry Bear, MD, PhD, a professor with the division of surgical oncology at Virginia Commonwealth University in Richmond. "It can be used for the express purpose of shrinking a tumor that might be too big for lumpectomy. For selected patients, if we’re able to shrink the tumor, we’re able to do a lumpectomy instead of having to remove the whole breast."
At one time, it was hoped that giving chemotherapy before surgery might give all women better treatment options. The idea was that neoadjuvant chemotherapy would offer better survival rates than post-operative chemotherapy because cancer cells would be killed earlier in the disease process. But such a survival advantage has not been demonstrated in studies. A review of nine clinical trials of neoadjuvant chemotherapy involving almost 4,000 women was published in February 2005 in the Journal of the National Cancer Institute (JNCI). The study researchers, from the University of Ioannina School of Medicine in Greece, found that women who received chemotherapy before surgery had similar rates of survival, disease progression and cancer spread as women who were treated with post-operative chemotherapy, which is known as adjuvant chemotherapy.
The researchers did find that the women who had neoadjuvant chemotherapy had higher rates of local recurrences, or recurrences in the breast and nearby lymph nodes. Local recurrences don’t hurt a woman’s chances of survival, but any return of the cancer in nearby tissue after the initial surgery means that a woman would most likely have to undergo a mastectomy after all. The researchers found that these recurrences were most likely to occur in women who did not have any surgery because their tumors had disappeared completely after the neoadjuvant chemotherapy.
And for women who do have surgery to remove the remains of their tumor after chemotherapy the procedure is often is often trickier. The goal of any surgery is to remove the cancer with a wide margin of tissue around it to ensure that you are getting all of the cancer cells out of the body. This wide margin is called a "negative" margin.
"If you’re doing surgery right away, you know where the cancer is, and we have a large body of knowledge that shows that if you take the cancer out with a large margin [around the tumor], there will be a low rate of recurrence." says Monica Morrow, MD, the chair of the department of surgery at the Fox Chase Cancer Center in Philadelphia. "But when some cancers die after chemotherapy, they die in a patchy fashion, so if you do surgery after chemotherapy, a negative margin might not mean the same thing." She adds that the greater possibility that part of the tumor will be left in the breast requires "a greater need for close communication between the surgeon, the pathologist and the radiation oncologist."
For now, neoadjuvant chemotherapy is only offered to women with a large tumor in a small breast who want a lumptectomy. But this approach to treatment may play a greater role in the future. Some researchers hope that neoadjuvant chemotherapy can one day be used to test the impact of a given chemotherapy drug on a particular tumor, allowing women to quickly switch to a more effective chemotherapy combination. But first scientists have to identify cancer markers that will indicate whether a chemotherapy drug is working.
"One of the other theoretical advantages to neoadjuvant chemotherapy—and this is really why it’s a very exciting focus for a lot of our research protocols—is that it allows us to look at features of the tumor that are associated with either a good response to a particular drug or no response to a particular drug." Dr. Bear says. "We are hoping that, eventually, we’ll get to a point where we can look at patient’s tumor with very sophisticated tests and be able to determine whether a particular tumor should be treated with drug A or drug B or whether neither one of those drugs is good."
"Neoadjuvant chemotherapy refers to giving chemotherapy upfront before we do surgery."
says Harry Bear, MD, PhD, a professor with the division of surgical oncology at Virginia Commonwealth University in Richmond. "It can be used for the express purpose of shrinking a tumor that might be too big for lumpectomy. For selected patients, if we’re able to shrink the tumor, we’re able to do a lumpectomy instead of having to remove the whole breast."
At one time, it was hoped that giving chemotherapy before surgery might give all women better treatment options. The idea was that neoadjuvant chemotherapy would offer better survival rates than post-operative chemotherapy because cancer cells would be killed earlier in the disease process. But such a survival advantage has not been demonstrated in studies. A review of nine clinical trials of neoadjuvant chemotherapy involving almost 4,000 women was published in February 2005 in the Journal of the National Cancer Institute (JNCI). The study researchers, from the University of Ioannina School of Medicine in Greece, found that women who received chemotherapy before surgery had similar rates of survival, disease progression and cancer spread as women who were treated with post-operative chemotherapy, which is known as adjuvant chemotherapy.
The researchers did find that the women who had neoadjuvant chemotherapy had higher rates of local recurrences, or recurrences in the breast and nearby lymph nodes. Local recurrences don’t hurt a woman’s chances of survival, but any return of the cancer in nearby tissue after the initial surgery means that a woman would most likely have to undergo a mastectomy after all. The researchers found that these recurrences were most likely to occur in women who did not have any surgery because their tumors had disappeared completely after the neoadjuvant chemotherapy.
And for women who do have surgery to remove the remains of their tumor after chemotherapy the procedure is often is often trickier. The goal of any surgery is to remove the cancer with a wide margin of tissue around it to ensure that you are getting all of the cancer cells out of the body. This wide margin is called a "negative" margin.
"If you’re doing surgery right away, you know where the cancer is, and we have a large body of knowledge that shows that if you take the cancer out with a large margin [around the tumor], there will be a low rate of recurrence." says Monica Morrow, MD, the chair of the department of surgery at the Fox Chase Cancer Center in Philadelphia. "But when some cancers die after chemotherapy, they die in a patchy fashion, so if you do surgery after chemotherapy, a negative margin might not mean the same thing." She adds that the greater possibility that part of the tumor will be left in the breast requires "a greater need for close communication between the surgeon, the pathologist and the radiation oncologist."
For now, neoadjuvant chemotherapy is only offered to women with a large tumor in a small breast who want a lumptectomy. But this approach to treatment may play a greater role in the future. Some researchers hope that neoadjuvant chemotherapy can one day be used to test the impact of a given chemotherapy drug on a particular tumor, allowing women to quickly switch to a more effective chemotherapy combination. But first scientists have to identify cancer markers that will indicate whether a chemotherapy drug is working.
"One of the other theoretical advantages to neoadjuvant chemotherapy—and this is really why it’s a very exciting focus for a lot of our research protocols—is that it allows us to look at features of the tumor that are associated with either a good response to a particular drug or no response to a particular drug." Dr. Bear says. "We are hoping that, eventually, we’ll get to a point where we can look at patient’s tumor with very sophisticated tests and be able to determine whether a particular tumor should be treated with drug A or drug B or whether neither one of those drugs is good."
Sunday, October 22, 2006
Breast cancer screening underutilized by ethnic women
Lack of information, modesty and a false sense of security may prevent women from immigrant backgrounds from having regular clinical breast examinations, says a Candian study. The Toronto study of South Asian immigrant women showed that although 83 per cent of the women surveyed had heard of clinical breast examination, only 38.5 per cent had ever had the exam - a concern since breast cancer is the most commonly diagnosed cancer among women in North America.
From Universoty of Toronto:Breast cancer screening underutilized by ethnic women
New immigrants less likely to get exams
Lack of information, modesty and a false sense of security may prevent women from immigrant backgrounds from having regular clinical breast examinations, says a study by the University of Toronto and the University Health Network (UHN).
A Toronto study of South Asian immigrant women, published in the July issue of the Journal of Immigrant Health, showed that although 83 per cent of the women surveyed had heard of clinical breast examination (CBE), only 38.5 per cent had ever had the exam - a concern since breast cancer is the most commonly diagnosed cancer among women in North America.
''Early detection of breast cancer increases the chance of survival, so having regular clinical breast examinations is important,'' says Farah Ahmad, a PhD candidate in medicine at U of T. Ahmad co-authored the study with Dr. Donna Stewart, a University Professor in psychiatry and obstetrics/gynecology at U of T and chair of the Women's Health Program at UHN. ''Because South Asian women are at low risk from breast cancer in their native countries, they don't realize that the risk changes once they are living in North America.
The U of T study, funded by the Canadian Breast Cancer Foundation, focused on Urdu- and Hindi-speaking women residing in urban areas. Researchers also found that the women who had been in Canada longest were more likely to have had a CBE. Overall, there were big gaps in knowledge about breast cancer risk and screening methods; only 7.4 per cent knew that mammograms were recommended every two years for women aged 50 and over. Less than half the women in the study knew that mammograms are universally covered by Canadian health insurance.
''Our study, although small, points to the value of having educational initiatives tailored to emphasize issues specific to the targeted community,'' said Ahmad.
From Universoty of Toronto:Breast cancer screening underutilized by ethnic women
New immigrants less likely to get exams
Lack of information, modesty and a false sense of security may prevent women from immigrant backgrounds from having regular clinical breast examinations, says a study by the University of Toronto and the University Health Network (UHN).
A Toronto study of South Asian immigrant women, published in the July issue of the Journal of Immigrant Health, showed that although 83 per cent of the women surveyed had heard of clinical breast examination (CBE), only 38.5 per cent had ever had the exam - a concern since breast cancer is the most commonly diagnosed cancer among women in North America.
''Early detection of breast cancer increases the chance of survival, so having regular clinical breast examinations is important,'' says Farah Ahmad, a PhD candidate in medicine at U of T. Ahmad co-authored the study with Dr. Donna Stewart, a University Professor in psychiatry and obstetrics/gynecology at U of T and chair of the Women's Health Program at UHN. ''Because South Asian women are at low risk from breast cancer in their native countries, they don't realize that the risk changes once they are living in North America.
The U of T study, funded by the Canadian Breast Cancer Foundation, focused on Urdu- and Hindi-speaking women residing in urban areas. Researchers also found that the women who had been in Canada longest were more likely to have had a CBE. Overall, there were big gaps in knowledge about breast cancer risk and screening methods; only 7.4 per cent knew that mammograms were recommended every two years for women aged 50 and over. Less than half the women in the study knew that mammograms are universally covered by Canadian health insurance.
''Our study, although small, points to the value of having educational initiatives tailored to emphasize issues specific to the targeted community,'' said Ahmad.
Patient's genes predict response to chemo for breast cancer
Breast cancer patients could find out whether they will respond positively to chemotherapy treatment by testing for the activity of certain genes. In a study published today in the Open Access journal, Journal of Translational Medicine, researchers analysed the genes expressed in the tumours of eighty-three patients with primary breast cancer. The researchers were able to predict which breast tumours would improve from chemotherapy in all cases of partial remission and nearly three quarters of the cases of complete remission based on the analysis of less than sixty genes present in the tumours. The authors of this study state that the ability to predict which patients will respond to chemotherapy, and which would not, would be a "powerful tool" in the treatment of breast cancer.
Olga Modlich and colleagues, from the University of Düsseldorf and Bayer HealthCare AG in Germany, analysed samples of breast tissue from five healthy individuals and tumour tissue from fifty-six breast cancer patients treated with preoperative systemic chemotherapy (PST) with a combination of the anti-cancer drugs epirubicin and cyclophosphamide. The genes present in the samples were analysed using a DNA microarray - a collection of microscopic DNA spots attached to a solid surface used to measure the expression levels of large numbers of genes simultaneously.
From the DNA microarray analysis the authors were able to identify a total of fifty-seven 'predictor' genes active in tumours: thirty-one genes associated with a favourable response and twenty-six genes associated with a poor response. The authors then tested the ability of these genes to predict the response of twenty-seven breast cancer patients, who were then treated with PST.
The predictor genes could be used to correctly predict the outcome of PST in all cases of partial remission and nearly 75% of cases of complete remission of primary tumours. According to the authors the use of microarray technology to identify genes that can predict response to chemotherapy could represent a powerful tool to identify patients for whom PST is the most appropriate, and would be the most successful form of treatment.
Currently, decisions about whether to use chemotherapy as a breast cancer treatment are based on factors such as patients' age and type and size of tumour. These factors do not provide sufficient information to tailor treatment to the individual patient. Nearly all breast cancer patients receive standard chemotherapy treatment, despite the potential for a poor response to therapy, adverse side effects and excess healthcare costs. According to the authors "the identification of molecular markers predictive of patients' responsiveness to treatment is becoming a central focus of research". The ability to predict a patient's response to chemotherapy for breast cancer would be of benefit to doctors and patients, shifting the focus away from a standard treatment for all patients and towards treatment based on predictions made from patients' genetic background.
From BioMed Central
Olga Modlich and colleagues, from the University of Düsseldorf and Bayer HealthCare AG in Germany, analysed samples of breast tissue from five healthy individuals and tumour tissue from fifty-six breast cancer patients treated with preoperative systemic chemotherapy (PST) with a combination of the anti-cancer drugs epirubicin and cyclophosphamide. The genes present in the samples were analysed using a DNA microarray - a collection of microscopic DNA spots attached to a solid surface used to measure the expression levels of large numbers of genes simultaneously.
From the DNA microarray analysis the authors were able to identify a total of fifty-seven 'predictor' genes active in tumours: thirty-one genes associated with a favourable response and twenty-six genes associated with a poor response. The authors then tested the ability of these genes to predict the response of twenty-seven breast cancer patients, who were then treated with PST.
The predictor genes could be used to correctly predict the outcome of PST in all cases of partial remission and nearly 75% of cases of complete remission of primary tumours. According to the authors the use of microarray technology to identify genes that can predict response to chemotherapy could represent a powerful tool to identify patients for whom PST is the most appropriate, and would be the most successful form of treatment.
Currently, decisions about whether to use chemotherapy as a breast cancer treatment are based on factors such as patients' age and type and size of tumour. These factors do not provide sufficient information to tailor treatment to the individual patient. Nearly all breast cancer patients receive standard chemotherapy treatment, despite the potential for a poor response to therapy, adverse side effects and excess healthcare costs. According to the authors "the identification of molecular markers predictive of patients' responsiveness to treatment is becoming a central focus of research". The ability to predict a patient's response to chemotherapy for breast cancer would be of benefit to doctors and patients, shifting the focus away from a standard treatment for all patients and towards treatment based on predictions made from patients' genetic background.
From BioMed Central
Test Predicts Risk of Breast Cancer Recurrence, Who Will Benefit From Chemo
A new test can predict both the risk of breast cancer recurrence and may identify women who will benefit most from chemotherapy, according to research supported by the National Cancer Institute (NCI), part of the National Institutes of Health, and performed in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Genomic Health Inc. These results suggest that almost half of over 50,000 U.S. women diagnosed with estrogen-dependent, lymph-node negative breast cancer* every year are at low risk for recurrence and may not need to go through the discomfort and side effects of chemotherapy.
From National Cancer Institute:
Molecular Test Can Predict Both the Risk of Breast Cancer Recurrence and Who Will Benefit From Chemotherapy
A new test can predict both the risk of breast cancer recurrence and may identify women who will benefit most from chemotherapy, according to research supported by the National Cancer Institute (NCI), part of the National Institutes of Health, and performed in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Genomic Health Inc. These results suggest that almost half of over 50,000 U.S. women diagnosed with estrogen-dependent, lymph-node negative breast cancer* every year are at low risk for recurrence and may not need to go through the discomfort and side effects of chemotherapy.
The test is based on levels of expression (increased or decreased) of a panel of cancer-related genes. This panel is used to predict whether estrogen-dependent breast cancer will come back, according to a study that will be published online in the New England Journal of Medicine on Friday, December 10, 2004**. Scientists on this study also will present new results on that day at San Antonio Breast Cancer Symposium indicating that the same test can predict which women benefit most from chemotherapy. Women with low risk of breast cancer recurrence--about half of the women in the recent study--do not appear to derive much benefit from chemotherapy.
The researchers used tissue samples and medical records from women enrolled in clinical trials of the cancer drug tamoxifen, which blocks the effect of estrogen on breast cancer cells. These women had a kind of breast cancer defined as estrogen receptor-positive, lymph node-negative. Each year, over 50,000 women are diagnosed with this kind of breast cancer, which needs estrogen to grow but has not spread to the lymph nodes. Currently, many women with this type of breast cancer in the United States do receive chemotherapy in addition to hormonal therapy.
Using samples from 447 patients and a collection of 250 genes in three independent preliminary studies, 16 cancer-related genes were found that worked best. The scientists created a formula that generates a ''recurrence score'' based on the expression patterns of these genes in a tumor sample. Ranging from 1 to 100, the recurrence score is a measure of the risk that a given cancer will recur***.
Prior to this research, analysis of the expression of genes was performed on tumor specimens that were frozen rather than on tissue prepared for routine pathologic evaluation (fixed and embedded). The expression analysis depended on measurement of RNA (the molecule necessary for the translation of a gene into a protein), and RNA is altered when tissues are fixed and embedded. Frozen tissues are generally not readily available in routine practice. Researchers at Genomic Health Inc. developed a method for performing these analyses on tissues embedded in paraffin wax. Their method allows them to use the altered RNA that is found in fixed tissue.
The results published in the New England Journal of Medicine validate the ability of the recurrence score to predict risk of recurrence. Using biopsy tissue and medical records from another NSABP tamoxifen trial, researchers divided 668 women into low, intermediate, and high risk of recurrence groups. Fifty-one percent were in the low risk group (with a score of less than 18); 22 percent were at intermediate risk (recurrence score 18 or higher but less than 31); 27 percent were at high risk (a score of 31 or higher).
These risk group divisions correlated well with the actual rates of recurrence of breast cancer after 10 years. There was a significant difference in recurrence rates between women in the low and high risk groups. In the low risk group, there was a 6.8 percent rate of recurrence at 10 years; in the intermediate and high risk categories these rates were 14.3 and 30.5 percent, respectively. Up to a recurrence score of 50, rates of recurrence increased continuously as the recurrence score increased. These trends held across age groups and tumor size.
''These results were generated perhaps a decade earlier than would have been possible if the researchers had not had access to biopsy tissue from the NSABP trials,'' notes Sheila E. Taube, Ph.D., associate director of NCI's Cancer Diagnosis Program.
The same 21-gene test has also been used to predict how beneficial chemotherapy will be for women with estrogen receptor-positive, lymph node-negative breast cancer for women on tamoxifen in NSABP trials. These results will be presented at the San Antonio Breast Cancer Symposium on December 10, 2004.
''NCI staff worked with the company, NSABP and experts from other NCI Cooperative Groups to develop an overall strategy to validate the test; this plan was fruitful and may lead to providing an important tool for physicians and women to use in considering breast cancer treatment decisions,'' said Taube.
In the treatment study, women with high recurrence scores, who are representative of about 25 percent of patients with this kind of breast cancer, had a large benefit from chemotherapy in terms of 10 year recurrence-free rates. Women with low recurrence scores, who represent about 50 percent of these patients, derived minimal benefits from chemotherapy. The group under study was not large enough to determine whether chemotherapy is detrimental to the low risk group.
''The test has the potential to change medical practice by sparing thousands of women each year from the harmful short- and long-term side effects associated with chemotherapy,'' said JoAnne Zujewski, M.D., senior investigator in NCI's Cancer Therapy Evaluation Program.
From National Cancer Institute:
Molecular Test Can Predict Both the Risk of Breast Cancer Recurrence and Who Will Benefit From Chemotherapy
A new test can predict both the risk of breast cancer recurrence and may identify women who will benefit most from chemotherapy, according to research supported by the National Cancer Institute (NCI), part of the National Institutes of Health, and performed in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Genomic Health Inc. These results suggest that almost half of over 50,000 U.S. women diagnosed with estrogen-dependent, lymph-node negative breast cancer* every year are at low risk for recurrence and may not need to go through the discomfort and side effects of chemotherapy.
The test is based on levels of expression (increased or decreased) of a panel of cancer-related genes. This panel is used to predict whether estrogen-dependent breast cancer will come back, according to a study that will be published online in the New England Journal of Medicine on Friday, December 10, 2004**. Scientists on this study also will present new results on that day at San Antonio Breast Cancer Symposium indicating that the same test can predict which women benefit most from chemotherapy. Women with low risk of breast cancer recurrence--about half of the women in the recent study--do not appear to derive much benefit from chemotherapy.
The researchers used tissue samples and medical records from women enrolled in clinical trials of the cancer drug tamoxifen, which blocks the effect of estrogen on breast cancer cells. These women had a kind of breast cancer defined as estrogen receptor-positive, lymph node-negative. Each year, over 50,000 women are diagnosed with this kind of breast cancer, which needs estrogen to grow but has not spread to the lymph nodes. Currently, many women with this type of breast cancer in the United States do receive chemotherapy in addition to hormonal therapy.
Using samples from 447 patients and a collection of 250 genes in three independent preliminary studies, 16 cancer-related genes were found that worked best. The scientists created a formula that generates a ''recurrence score'' based on the expression patterns of these genes in a tumor sample. Ranging from 1 to 100, the recurrence score is a measure of the risk that a given cancer will recur***.
Prior to this research, analysis of the expression of genes was performed on tumor specimens that were frozen rather than on tissue prepared for routine pathologic evaluation (fixed and embedded). The expression analysis depended on measurement of RNA (the molecule necessary for the translation of a gene into a protein), and RNA is altered when tissues are fixed and embedded. Frozen tissues are generally not readily available in routine practice. Researchers at Genomic Health Inc. developed a method for performing these analyses on tissues embedded in paraffin wax. Their method allows them to use the altered RNA that is found in fixed tissue.
The results published in the New England Journal of Medicine validate the ability of the recurrence score to predict risk of recurrence. Using biopsy tissue and medical records from another NSABP tamoxifen trial, researchers divided 668 women into low, intermediate, and high risk of recurrence groups. Fifty-one percent were in the low risk group (with a score of less than 18); 22 percent were at intermediate risk (recurrence score 18 or higher but less than 31); 27 percent were at high risk (a score of 31 or higher).
These risk group divisions correlated well with the actual rates of recurrence of breast cancer after 10 years. There was a significant difference in recurrence rates between women in the low and high risk groups. In the low risk group, there was a 6.8 percent rate of recurrence at 10 years; in the intermediate and high risk categories these rates were 14.3 and 30.5 percent, respectively. Up to a recurrence score of 50, rates of recurrence increased continuously as the recurrence score increased. These trends held across age groups and tumor size.
''These results were generated perhaps a decade earlier than would have been possible if the researchers had not had access to biopsy tissue from the NSABP trials,'' notes Sheila E. Taube, Ph.D., associate director of NCI's Cancer Diagnosis Program.
The same 21-gene test has also been used to predict how beneficial chemotherapy will be for women with estrogen receptor-positive, lymph node-negative breast cancer for women on tamoxifen in NSABP trials. These results will be presented at the San Antonio Breast Cancer Symposium on December 10, 2004.
''NCI staff worked with the company, NSABP and experts from other NCI Cooperative Groups to develop an overall strategy to validate the test; this plan was fruitful and may lead to providing an important tool for physicians and women to use in considering breast cancer treatment decisions,'' said Taube.
In the treatment study, women with high recurrence scores, who are representative of about 25 percent of patients with this kind of breast cancer, had a large benefit from chemotherapy in terms of 10 year recurrence-free rates. Women with low recurrence scores, who represent about 50 percent of these patients, derived minimal benefits from chemotherapy. The group under study was not large enough to determine whether chemotherapy is detrimental to the low risk group.
''The test has the potential to change medical practice by sparing thousands of women each year from the harmful short- and long-term side effects associated with chemotherapy,'' said JoAnne Zujewski, M.D., senior investigator in NCI's Cancer Therapy Evaluation Program.
Left handedness may be linked to breast cancer risk
Left handedness may be linked to an increased risk of breast cancer, finds new research published online by the BMJ today (26 September 2005).
Researchers in the Netherlands examined the relation between handedness and incidence of breast cancer in over 12,000 healthy, middle aged women born between 1932 and 1941.
Body measurements were taken and risk factors such as social and economic status, smoking habits, family history of breast cancer, and reproductive history were recorded.
They found that left handed women were more than twice as likely to develop premenopausal breast cancer as non-left handed women. Adjusting for risk factors hardly affected the overall association.
The origin of the association may lie in exposure to high levels of sex hormones before birth, which can induce left handedness as well as changes in breast tissue, say the authors.
"Although the underlying mechanisms remain elusive, our results support the hypothesis that left handedness is related to increased risk of breast cancer," they conclude.
From British Medical Journal
Researchers in the Netherlands examined the relation between handedness and incidence of breast cancer in over 12,000 healthy, middle aged women born between 1932 and 1941.
Body measurements were taken and risk factors such as social and economic status, smoking habits, family history of breast cancer, and reproductive history were recorded.
They found that left handed women were more than twice as likely to develop premenopausal breast cancer as non-left handed women. Adjusting for risk factors hardly affected the overall association.
The origin of the association may lie in exposure to high levels of sex hormones before birth, which can induce left handedness as well as changes in breast tissue, say the authors.
"Although the underlying mechanisms remain elusive, our results support the hypothesis that left handedness is related to increased risk of breast cancer," they conclude.
From British Medical Journal
Monday, October 16, 2006
Communities Key to Lowering Cancer Risk
(HealthDay News) -- Weight control, exercise, a healthy diet high in plant-based foods, and limited alcohol consumption are the major points in the updated Nutrition and Physical Activity Guidelines for Cancer Prevention, recently released by the American Cancer Association.
In addition, the guidelines emphasize the importance of community efforts, noting that a supportive social environment is vital in making it possible for people at all levels of society to have the opportunity to choose behaviors that reduce their cancer risk.
According to the guidelines, public, private, and community organizations should work to increase access to healthy foods in schools, workplaces, and communities and to provide safe, enjoyable and accessible environments for physical activity in schools and for transportation and recreation in communities.
"For years, we've told people what habits to adopt to lower their cancer risk, but it has become increasingly clear we need to create environments that make it easier to make healthy choices," report co-author Colleen Doyle, director of nutrition and physical activity for the American Cancer Society, said in a prepared statement.
"These guidelines underscore what communities can and should be doing to make these health habits achievable. Just as excise taxes and smoke-free laws have been critical to reducing tobacco's cancer toll, community action is essential to create a social environment that promotes healthy food choices and physical activity," Doyle said.
Recent evidence shows that, for non-smokers, weight control, physical activity, and dietary choices are the most important modifiable cancer risk factors, the American Cancer Society said.
A third of the more than 500,000 cancer deaths in the United States each year are attributable to poor diet and physical activity habits. That's about the same portion as cancer deaths caused by tobacco.
The guidelines were published in the September/October issue of CA: A Cancer Journal for Clinicians.
More information
The American Cancer Society has more about cancer prevention.
In addition, the guidelines emphasize the importance of community efforts, noting that a supportive social environment is vital in making it possible for people at all levels of society to have the opportunity to choose behaviors that reduce their cancer risk.
According to the guidelines, public, private, and community organizations should work to increase access to healthy foods in schools, workplaces, and communities and to provide safe, enjoyable and accessible environments for physical activity in schools and for transportation and recreation in communities.
"For years, we've told people what habits to adopt to lower their cancer risk, but it has become increasingly clear we need to create environments that make it easier to make healthy choices," report co-author Colleen Doyle, director of nutrition and physical activity for the American Cancer Society, said in a prepared statement.
"These guidelines underscore what communities can and should be doing to make these health habits achievable. Just as excise taxes and smoke-free laws have been critical to reducing tobacco's cancer toll, community action is essential to create a social environment that promotes healthy food choices and physical activity," Doyle said.
Recent evidence shows that, for non-smokers, weight control, physical activity, and dietary choices are the most important modifiable cancer risk factors, the American Cancer Society said.
A third of the more than 500,000 cancer deaths in the United States each year are attributable to poor diet and physical activity habits. That's about the same portion as cancer deaths caused by tobacco.
The guidelines were published in the September/October issue of CA: A Cancer Journal for Clinicians.
More information
The American Cancer Society has more about cancer prevention.
Thursday, October 05, 2006
Appetite-Fighting Molecule May Fight Obesity
(HealthDay News) -- Japanese researchers have discovered a naturally occurring molecule that suppresses appetite in mammals, raising hopes that it might one day treat obesity in humans.
Over a period of 10 days, rats that received a continuous infusion of the compound, called nesfatin-1, ate significantly less food than untreated rats. They also gained significantly less weight than untreated rats (an average of 12.6 grams vs. an average of 30.4 grams), apparently without any adverse effects.
The findings, published in the Oct. 1 online edition of Nature, "indicate that nesfatin-1 might be a useful target for the development of drug therapies to treat obese persons," the study authors concluded.
A team led by Dr. Masatomo Mori, of the department of medicine and molecular science at Gunma University Graduate School of Medicine, in Maebashi, say they discovered the molecule after analyzing 596 genes, nine of which are expressed in both the brains and fat tissues of mammals.
The researchers narrowed their search to NUCB2, a protein secreted by the hypothalamus, a brain region that helps regulate appetite. They suspect that a fragment of NUCB2 -- a molecule they dubbed "nesfatin-1" -- plays a key role in appetite control.
To test their theory, they injected nestfatin-1 into the hypothalamus regions of a special strain of obese rats. These rats carried a gene mutation that led them to resist the effects of leptin, a hormone thought to play a role in obesity. Obese people are also thought to be somewhat resistant to leptin's appetite-dampening effects.
The injections appeared to decrease appetite in the rats, the researchers report, "suggesting that nesfatin-1 may be effective in obese persons with leptin resistance," Mori said.
In fact, "the dose we used had the same potency as leptin in reducing appetite," he said. Compared to rats that didn't get the injections, rats receiving nesfatin-1 ate much less and cut their weight gain by more than half.
In another experiment, the researchers used a special antibody to block nesfatin-1 uptake. The result: the rats' appetites rebounded and they quickly put on weight.
There were no major side effects, Mori said, and, "so far, we have not observed any adverse behavioral changes in rats receiving nesfatin-1."
Because brain injections are not a feasible treatment for obese humans, Mori and his team have been testing other ways of administering nesfatin-1 to obese rats.
"We have preliminary data showing that peripheral [non-brain] injection of nesfatin-1 is also effective to reduce food intake in rats," Mori said. "So we are optimistic that subcutaneous injection of nesfatin-1 may become available to treat human subjects with obesity."
Overweight and obesity are a global epidemic, in developing as well as developed nations. Of the estimated 1 billion adults worldwide who are overweight, about 300 million are considered obese, according to the World Health Organization.
Obesity is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension and stroke, and some forms of cancer.
"We are really hopeful that nesfatin-1 and [similar molecules] will prove useful in treating obese persons in the near feature," Mori said.
More information
There's more on research into fighting obesity at the U.S. National Institutes of Health.
Over a period of 10 days, rats that received a continuous infusion of the compound, called nesfatin-1, ate significantly less food than untreated rats. They also gained significantly less weight than untreated rats (an average of 12.6 grams vs. an average of 30.4 grams), apparently without any adverse effects.
The findings, published in the Oct. 1 online edition of Nature, "indicate that nesfatin-1 might be a useful target for the development of drug therapies to treat obese persons," the study authors concluded.
A team led by Dr. Masatomo Mori, of the department of medicine and molecular science at Gunma University Graduate School of Medicine, in Maebashi, say they discovered the molecule after analyzing 596 genes, nine of which are expressed in both the brains and fat tissues of mammals.
The researchers narrowed their search to NUCB2, a protein secreted by the hypothalamus, a brain region that helps regulate appetite. They suspect that a fragment of NUCB2 -- a molecule they dubbed "nesfatin-1" -- plays a key role in appetite control.
To test their theory, they injected nestfatin-1 into the hypothalamus regions of a special strain of obese rats. These rats carried a gene mutation that led them to resist the effects of leptin, a hormone thought to play a role in obesity. Obese people are also thought to be somewhat resistant to leptin's appetite-dampening effects.
The injections appeared to decrease appetite in the rats, the researchers report, "suggesting that nesfatin-1 may be effective in obese persons with leptin resistance," Mori said.
In fact, "the dose we used had the same potency as leptin in reducing appetite," he said. Compared to rats that didn't get the injections, rats receiving nesfatin-1 ate much less and cut their weight gain by more than half.
In another experiment, the researchers used a special antibody to block nesfatin-1 uptake. The result: the rats' appetites rebounded and they quickly put on weight.
There were no major side effects, Mori said, and, "so far, we have not observed any adverse behavioral changes in rats receiving nesfatin-1."
Because brain injections are not a feasible treatment for obese humans, Mori and his team have been testing other ways of administering nesfatin-1 to obese rats.
"We have preliminary data showing that peripheral [non-brain] injection of nesfatin-1 is also effective to reduce food intake in rats," Mori said. "So we are optimistic that subcutaneous injection of nesfatin-1 may become available to treat human subjects with obesity."
Overweight and obesity are a global epidemic, in developing as well as developed nations. Of the estimated 1 billion adults worldwide who are overweight, about 300 million are considered obese, according to the World Health Organization.
Obesity is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension and stroke, and some forms of cancer.
"We are really hopeful that nesfatin-1 and [similar molecules] will prove useful in treating obese persons in the near feature," Mori said.
More information
There's more on research into fighting obesity at the U.S. National Institutes of Health.
ADHD Raises Kids' Health Costs Even Before Diagnosis
(HealthDay News) -- In the two years before and after they're diagnosed with attention-deficit hyperactivity disorder (ADHD), children with the condition typically use more health-care services than other children, U.S. research shows.
It also found that white children with ADHD accumulate more expenses than other children with the disorder.
Researchers in California analyzed health-care costs for more than 3,100 children, aged 2 to 10, who were diagnosed with ADHD between 1996 and 2004. They then compared those expenditures to health-care costs for more than 15,000 children without ADHD.
Compared to children without ADHD, those with the condition had average health care costs that were $488 higher in the second year before their diagnosis, $678 higher in the year before diagnosis, $1,328 higher in the year following diagnosis, and $1,040 higher in the second year after diagnosis.
Compared with white children with ADHD, Asian, black and Hispanic children showed lower annual costs for ADHD medications. Overall spending on ADHD services for Asian children was 30 percent lower ($221) than for white children, the study found.
The study was published in the October issue of the Archives of Pediatrics & Adolescent Medicine.
"Parents commonly state that behavioral problems predate their child's ADHD diagnosis, often by several years, and these problems may affect their use of health services," said a team led by G. Thomas Ray of the Kaiser Permanente Medical Care Program in Oakland.
"In our study sample, costs were significantly higher in the two years before the index date among children subsequently diagnosed with ADHD, and costs remained higher for at least two years following the initial ADHD diagnosis," the researchers noted. "Much of the excess cost was due to increased pediatric and psychiatric services, which were higher in the first year after diagnosis than in the second year."
Cultural acceptance of ADHD diagnosis and treatment could explain ethnic differences in costs and use of ADHD medications, the study authors said.
More information
The U.S. National Institute of Mental Health has more about ADHD.
It also found that white children with ADHD accumulate more expenses than other children with the disorder.
Researchers in California analyzed health-care costs for more than 3,100 children, aged 2 to 10, who were diagnosed with ADHD between 1996 and 2004. They then compared those expenditures to health-care costs for more than 15,000 children without ADHD.
Compared to children without ADHD, those with the condition had average health care costs that were $488 higher in the second year before their diagnosis, $678 higher in the year before diagnosis, $1,328 higher in the year following diagnosis, and $1,040 higher in the second year after diagnosis.
Compared with white children with ADHD, Asian, black and Hispanic children showed lower annual costs for ADHD medications. Overall spending on ADHD services for Asian children was 30 percent lower ($221) than for white children, the study found.
The study was published in the October issue of the Archives of Pediatrics & Adolescent Medicine.
"Parents commonly state that behavioral problems predate their child's ADHD diagnosis, often by several years, and these problems may affect their use of health services," said a team led by G. Thomas Ray of the Kaiser Permanente Medical Care Program in Oakland.
"In our study sample, costs were significantly higher in the two years before the index date among children subsequently diagnosed with ADHD, and costs remained higher for at least two years following the initial ADHD diagnosis," the researchers noted. "Much of the excess cost was due to increased pediatric and psychiatric services, which were higher in the first year after diagnosis than in the second year."
Cultural acceptance of ADHD diagnosis and treatment could explain ethnic differences in costs and use of ADHD medications, the study authors said.
More information
The U.S. National Institute of Mental Health has more about ADHD.
Hormone Therapy Ups Ovarian-Cancer Risk
(HealthDay News) -- The universe of possible health risks associated with hormone therapy just got bigger.
New research suggests that prolonged use of hormone therapy in postmenopausal women increases slightly the risk of developing ovarian cancer.
The risk does need confirmation in other studies and also needs to be weighed against other factors, the researchers cautioned.
"We've seen a growing body of evidence linking unopposed estrogen and estrogen-plus-progestin to an increased risk of ovarian cancer," said study author James V. Lacey Jr., an epidemiologist with the National Cancer Institute. "There are still some outstanding questions, but this adds more data that there is a slightly increased risk of ovarian cancer among women who used [this] hormone therapy for long durations."
Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, added, "It's another caution, but it's probably not going to be as applicable today as 10 years ago when women went on hormone therapy for longer durations."
Another study in the same publication, the Oct. 4 issue of the Journal of the National Cancer Institute, found that high levels of natural sex hormones, including estrogen, were associated with an increased risk of breast cancer in premenopausal women.
Concerns about hormone replacement therapy (HRT) were initially raised by the Women's Health Initiative (WHI), a landmark U.S. study involving 27,000 participants. Researchers halted the WHI study in 2002, after they found the regimen entailed more health risks -- most notably an increased risk for breast cancer and stroke -- than benefits.
There has been conflicting information, however, regarding HRT and ovarian cancer.
The authors of the first study found that, among a group of almost 100,000 women aged 50 to 71, those with a hysterectomy who used estrogen alone for a decade or more had almost double the risk of ovarian cancer than those who received no HRT.
Women who had not undergone a hysterectomy and who used estrogen plus progestin in sequence or continuously for five or more years also had a higher risk, compared with women who used no HRT.
But this finding probably won't change medical practice, Lichtenfeld said. "To me, the message remains pretty much the same," he said. "Currently, if you go on HRT, the recommendation based on the WHI is to go on for as short a period as possible."
And other studies on HRT and ovarian cancer would be helpful. "Because this is a rare cancer, it's even more important that we see whether other studies can replicate the findings," Lacey said.
The authors of the second study looked at blood samples from 18,521 premenopausal women and found that women with high levels of a naturally occurring type of estrogen called estradiol during the pre-ovulation phase of their menstrual cycle had a higher risk of developing breast cancer. Higher levels of testosterone and androstenedione in both the pre- and post-ovulation phases were also associated with an increased risk.
But again, nothing is likely to change in doctors' offices as a result of this finding.
"This is an interesting study. It does suggest that there's a relationship, but it won't change anything we recommend to women at this time," Lichtenfeld said. "If we were able to identify those with higher circulating levels, we might change recommendations in terms of surveillance, but the reality is that this is not something that's commonly measured."
Perhaps the bigger priority, Lichtenfeld added, is making sure women get mammograms in the first place. "We can't lose sight of the real message -- that women at average risk for breast cancer over the age of 40 need to get mammograms annually," he said.
A third study in the same issue of the journal found sad news for breast-cancer survivors: They have an increased risk of suicide for up to 30 years after diagnosis. The cumulative risk of suicide 30 years after a breast-cancer diagnosis was 0.2 percent, or 37 percent higher than the general population.
According to the study, women with breast cancer account for one in five of all cancer survivors in the United States, a total of about 2 million people in 2001.
More information
For more on HRT, visit the U.S. National Library of Medicine.
New research suggests that prolonged use of hormone therapy in postmenopausal women increases slightly the risk of developing ovarian cancer.
The risk does need confirmation in other studies and also needs to be weighed against other factors, the researchers cautioned.
"We've seen a growing body of evidence linking unopposed estrogen and estrogen-plus-progestin to an increased risk of ovarian cancer," said study author James V. Lacey Jr., an epidemiologist with the National Cancer Institute. "There are still some outstanding questions, but this adds more data that there is a slightly increased risk of ovarian cancer among women who used [this] hormone therapy for long durations."
Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, added, "It's another caution, but it's probably not going to be as applicable today as 10 years ago when women went on hormone therapy for longer durations."
Another study in the same publication, the Oct. 4 issue of the Journal of the National Cancer Institute, found that high levels of natural sex hormones, including estrogen, were associated with an increased risk of breast cancer in premenopausal women.
Concerns about hormone replacement therapy (HRT) were initially raised by the Women's Health Initiative (WHI), a landmark U.S. study involving 27,000 participants. Researchers halted the WHI study in 2002, after they found the regimen entailed more health risks -- most notably an increased risk for breast cancer and stroke -- than benefits.
There has been conflicting information, however, regarding HRT and ovarian cancer.
The authors of the first study found that, among a group of almost 100,000 women aged 50 to 71, those with a hysterectomy who used estrogen alone for a decade or more had almost double the risk of ovarian cancer than those who received no HRT.
Women who had not undergone a hysterectomy and who used estrogen plus progestin in sequence or continuously for five or more years also had a higher risk, compared with women who used no HRT.
But this finding probably won't change medical practice, Lichtenfeld said. "To me, the message remains pretty much the same," he said. "Currently, if you go on HRT, the recommendation based on the WHI is to go on for as short a period as possible."
And other studies on HRT and ovarian cancer would be helpful. "Because this is a rare cancer, it's even more important that we see whether other studies can replicate the findings," Lacey said.
The authors of the second study looked at blood samples from 18,521 premenopausal women and found that women with high levels of a naturally occurring type of estrogen called estradiol during the pre-ovulation phase of their menstrual cycle had a higher risk of developing breast cancer. Higher levels of testosterone and androstenedione in both the pre- and post-ovulation phases were also associated with an increased risk.
But again, nothing is likely to change in doctors' offices as a result of this finding.
"This is an interesting study. It does suggest that there's a relationship, but it won't change anything we recommend to women at this time," Lichtenfeld said. "If we were able to identify those with higher circulating levels, we might change recommendations in terms of surveillance, but the reality is that this is not something that's commonly measured."
Perhaps the bigger priority, Lichtenfeld added, is making sure women get mammograms in the first place. "We can't lose sight of the real message -- that women at average risk for breast cancer over the age of 40 need to get mammograms annually," he said.
A third study in the same issue of the journal found sad news for breast-cancer survivors: They have an increased risk of suicide for up to 30 years after diagnosis. The cumulative risk of suicide 30 years after a breast-cancer diagnosis was 0.2 percent, or 37 percent higher than the general population.
According to the study, women with breast cancer account for one in five of all cancer survivors in the United States, a total of about 2 million people in 2001.
More information
For more on HRT, visit the U.S. National Library of Medicine.
Plastics Chemical Might Promote Breast Cancer
(HealthDay News) -- A chemical found in the harder plastics that make up CD cases, water-cooler jugs and other objects people handle might help promote breast cancer, researchers say.
The chemical -- a "pseudo-estrogen" called bisphenol-A -- appears to be preferentially absorbed by breast tumor cells, according to a new study published in the Aug. 28 issue of Chemistry & Biology.
While the new research doesn't give any definitive answer on BPA's potential role in breast cancer, American researchers say they have uncovered a biological mechanism that allows the compound to concentrate in tumor cells.
Healthy cells don't readily absorb bisphenol sulfate, one of the body's metabolized forms of BPA. So, many experts have assumed the chemical might be harmless.
However, "it turns out that breast tumor cells are different than normal cells," lead researcher Theodore Widlanski of Indiana University, said. "We showed that breast tumor cells actually convert bisphenol sulfate back into bisphenol-A, which can then be taken up into tumor cells."
"These guys were aiming at what I'd say was the 'missing link,'" added Patricia Hunt, a molecular bioscience professor at Washington State University who has conducted her own studies suggesting a link between BPA and birth defects in mice. "This is a first step, and a really important first step," she said.
The effects of BPA on human health -- if any -- have been hotly debated. Previous studies have linked even small exposures to prostate abnormalities in mice that suggest -- but do not prove -- a link between the plastics chemical and human prostate cancer.
Other studies, including Hunt's, have theorized that embryonic and fetal exposures to BPA might trigger chromosomal changes that, in turn, could raise risks for mental retardation and birth defects.
BPA is a raw material used in the manufacture of hard, clear plastic products -- everything from electronics parts to food-storage containers and baby bottles. It is not found in softer, more flexible products such as single-serving water bottles.
The chemical is known a "pseudo-estrogen" because it is one of a number of natural or synthetic materials that can be taken into human cells and trigger estrogenic effects. But unlike estrogen, BPA undergoes chemical modifications as it enters the body, which makes its absorption by healthy human cells nearly impossible.
Specifically, the addition of a sulfate molecule to BPA keeps it from permeating the healthy cell's outer membrane. But would the same phenomenon hold true for malignant cells, researchers wondered?
In a laboratory study using human breast cancer cell lines, the Indiana researchers, along with scientists from the University of California at Berkley, found that BPA appeared to concentrate in tumor cells.
"We found no BPA in the medium the cells were grown in," Widlanski noted.
The key, according to Widlanski, is that the breast tumor cell carries an enzyme on its surface that strips sulfate molecules away from BPA. "Healthy cells don't have this property," he said. Once inside the tumor cell, BPA might encourage the cell's survival and proliferation, in the same way that estrogen does.
Widlanski cautioned, however, that his team's study had only uncovered a potential mechanism linking BPA to the promotion of breast cancer. Whether this mechanism actually occurs in real life is tough to prove, he said, as is the notion that BPA exposure plays a significant role in breast cancer.
The bottom line, according to Widlanski: "If you weren't alarmed yesterday about BPA, then you shouldn't be alarmed today. Nothing we have shown changes the innate danger. We have just reported a mechanism."
The plastics industry strongly defended its products.
"BPA has been extensively studied for its potential to cause cancer, including lifetime studies in rats and mice," said Steven Hentges, executive director of the Polycarbonate Business Unit at the American Plastics Council, which represents the industry.
He added that governments around the world have also commissioned their own studies on BPA, "and, in every case, have concluded that BPA is not likely to pose a carcinogenic risk to humans."
Hentges said the study also has serious flaws.
"First of all, it's an in vitro study," he said. "You can't extrapolate from a cell culture and say much of anything about breast cancer." And, he said, tests conducted recently by the U.S. Centers for Disease Control and Prevention (CDC) found average levels of BPA in human urine to be infinitesimally small -- about one part per billion.
Widlanski agreed that short-term, in vitro studies can never fully explain human disease. He also agreed that urine and blood concentrations of BPA metabolites in humans are much, much smaller than exposures used in this study.
"Unfortunately, we simply can't mimic long-term exposure to bisphenol A," he said, since it's unethical to give human test volunteers any chemical with an unproven safety record, especially over the long term.
"So, we have to use a larger concentration to mimic the effects of long-term exposure," he said. "No one knows if that's a valid way to do that or not." Animal studies are a logical next step, he said, but they can never fully replicate potential effects in humans.
"The real crux of the matter is that we are surrounded in our environment by chemicals that are pseudo-estrogenic, not just BPA," Widlanski added. "It's the cumulative effect of all of these compounds together that one needs to worry about."
Hunt said the new study does provide "badly needed mechanistic data" on a suspect compound.
"There's a body of data that's out there suggesting [BPA] exerts a pretty powerful effect on a number of different tissues," she said. "There have been studies of the developing embryo, and studies looking at the development of prostate tissue. This provides a way of understanding how this chemical may exert its effect."
More information
For more on breast cancer, head to the American Cancer Society.
The chemical -- a "pseudo-estrogen" called bisphenol-A -- appears to be preferentially absorbed by breast tumor cells, according to a new study published in the Aug. 28 issue of Chemistry & Biology.
While the new research doesn't give any definitive answer on BPA's potential role in breast cancer, American researchers say they have uncovered a biological mechanism that allows the compound to concentrate in tumor cells.
Healthy cells don't readily absorb bisphenol sulfate, one of the body's metabolized forms of BPA. So, many experts have assumed the chemical might be harmless.
However, "it turns out that breast tumor cells are different than normal cells," lead researcher Theodore Widlanski of Indiana University, said. "We showed that breast tumor cells actually convert bisphenol sulfate back into bisphenol-A, which can then be taken up into tumor cells."
"These guys were aiming at what I'd say was the 'missing link,'" added Patricia Hunt, a molecular bioscience professor at Washington State University who has conducted her own studies suggesting a link between BPA and birth defects in mice. "This is a first step, and a really important first step," she said.
The effects of BPA on human health -- if any -- have been hotly debated. Previous studies have linked even small exposures to prostate abnormalities in mice that suggest -- but do not prove -- a link between the plastics chemical and human prostate cancer.
Other studies, including Hunt's, have theorized that embryonic and fetal exposures to BPA might trigger chromosomal changes that, in turn, could raise risks for mental retardation and birth defects.
BPA is a raw material used in the manufacture of hard, clear plastic products -- everything from electronics parts to food-storage containers and baby bottles. It is not found in softer, more flexible products such as single-serving water bottles.
The chemical is known a "pseudo-estrogen" because it is one of a number of natural or synthetic materials that can be taken into human cells and trigger estrogenic effects. But unlike estrogen, BPA undergoes chemical modifications as it enters the body, which makes its absorption by healthy human cells nearly impossible.
Specifically, the addition of a sulfate molecule to BPA keeps it from permeating the healthy cell's outer membrane. But would the same phenomenon hold true for malignant cells, researchers wondered?
In a laboratory study using human breast cancer cell lines, the Indiana researchers, along with scientists from the University of California at Berkley, found that BPA appeared to concentrate in tumor cells.
"We found no BPA in the medium the cells were grown in," Widlanski noted.
The key, according to Widlanski, is that the breast tumor cell carries an enzyme on its surface that strips sulfate molecules away from BPA. "Healthy cells don't have this property," he said. Once inside the tumor cell, BPA might encourage the cell's survival and proliferation, in the same way that estrogen does.
Widlanski cautioned, however, that his team's study had only uncovered a potential mechanism linking BPA to the promotion of breast cancer. Whether this mechanism actually occurs in real life is tough to prove, he said, as is the notion that BPA exposure plays a significant role in breast cancer.
The bottom line, according to Widlanski: "If you weren't alarmed yesterday about BPA, then you shouldn't be alarmed today. Nothing we have shown changes the innate danger. We have just reported a mechanism."
The plastics industry strongly defended its products.
"BPA has been extensively studied for its potential to cause cancer, including lifetime studies in rats and mice," said Steven Hentges, executive director of the Polycarbonate Business Unit at the American Plastics Council, which represents the industry.
He added that governments around the world have also commissioned their own studies on BPA, "and, in every case, have concluded that BPA is not likely to pose a carcinogenic risk to humans."
Hentges said the study also has serious flaws.
"First of all, it's an in vitro study," he said. "You can't extrapolate from a cell culture and say much of anything about breast cancer." And, he said, tests conducted recently by the U.S. Centers for Disease Control and Prevention (CDC) found average levels of BPA in human urine to be infinitesimally small -- about one part per billion.
Widlanski agreed that short-term, in vitro studies can never fully explain human disease. He also agreed that urine and blood concentrations of BPA metabolites in humans are much, much smaller than exposures used in this study.
"Unfortunately, we simply can't mimic long-term exposure to bisphenol A," he said, since it's unethical to give human test volunteers any chemical with an unproven safety record, especially over the long term.
"So, we have to use a larger concentration to mimic the effects of long-term exposure," he said. "No one knows if that's a valid way to do that or not." Animal studies are a logical next step, he said, but they can never fully replicate potential effects in humans.
"The real crux of the matter is that we are surrounded in our environment by chemicals that are pseudo-estrogenic, not just BPA," Widlanski added. "It's the cumulative effect of all of these compounds together that one needs to worry about."
Hunt said the new study does provide "badly needed mechanistic data" on a suspect compound.
"There's a body of data that's out there suggesting [BPA] exerts a pretty powerful effect on a number of different tissues," she said. "There have been studies of the developing embryo, and studies looking at the development of prostate tissue. This provides a way of understanding how this chemical may exert its effect."
More information
For more on breast cancer, head to the American Cancer Society.
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