Goserelin Improves Long-term Survival In Premenopausal Women With Early Breast Cancer, Study Shows

Goserelin, a lutenizing hormone-releasing hormone agonist, reduces the long-term risk of disease recurrence and deaths in premenopausal women with early breast cancer who did not take tamoxifen, according to trial data.

Systematic reviews have shown that lutenizing hormone-releasing hormone agonists, including goserelin, reduce the risk of disease recurrence and death due to breast cancer in premenopausal women. However the long-term impact of goserelin was not known, particularly in comparison to women who did or did not take tamoxifen.

Women with breast cancer were randomly assigned to take goserelin (Zoladex), tamoxifen, both agents, or neither drug for two years in the Zoladex in Premenopausal Patients study. In this analysis, which included 2,706 women, Allan Hackshaw, of the Cancer Research UK Trials Centre at University College London, and colleagues examined the long-term impact of the agents on various outcomes, including the risk of the cancer returning and the risk of dying from breast cancer or any cause.

The effect of two years of goserelin treatment was comparable to that conferred by two years of tamoxifen. Among patients who took goserelin alone, there were 13.9 fewer events per 100 women 15 years after starting treatment, compared with those who did not take either drug. Among women who took both drugs, the benefit of adding goserelin to tamoxifen was smaller (2.8 fewer events per 100 patients) and did not reach statistical significance.

The number of breast cancer deaths was lower by 8.5 per 100 women in those who took goserelin alone, compared to those who took neither drug. The difference was statistically significant. Among those who added goserelin to tamoxifen, there was an additional reduction of 2.6 deaths per 100 women. But again, the additional reduction was not statistically significant.

"In summary, long-term follow-up of our large trial showed that goserelin had a demonstrable effect on survival and recurrence 15 years after starting treatment and is as effective as tamoxifen when each are given for 2 years," the authors write. "It may be that women who are unlikely to complete 5 years of tamoxifen tablets may prefer 2 years of goserelin injections."

New Genomic Test Can Personalize Breast Cancer Treatment

A set of 50 genes can be used to reliably identify the four known types of breast cancer, according to research conducted at Washington University School of Medicine in St. Louis and collaborating institutions. Using this 50-gene set, oncologists can potentially predict the most effective therapy for each breast tumor type and thereby personalize breast cancer treatment for all patients.

"Unlike a widely used genomic test that applies only to lymph-node negative, estrogen-receptor positive breast cancer, this new genomic test is broadly applicable for all women diagnosed with breast cancer," says breast cancer specialist Matthew Ellis, M.D., Ph.D., a member of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University.

The study was reported in the Journal of Clinical Oncology. Ellis' collaborators include co-authors Charles Perou, Ph.D., associate professor of genetics and pathology at the University of North Carolina at Chapel Hill School of Medicine, Philip S. Bernard, M.D., assistant professor of pathology and medical director of the molecular pathology laboratory at the University of Utah Huntsman Cancer Institute, and Torsten Nielsen, M.D., Ph.D., assistant professor of pathology and laboratory medicine at the University of British Columbia.

Breast cancer results from genetic abnormalities in breast tissue, but not all breast cancers have identical genetic alterations. Ellis and his colleagues analyzed the gene activity of more than 1,000 breast tumors to identify and validate the genetic signature of each of the four types of breast cancer. Although the cancer types are distinguished by thousands of genetic differences, the researchers were able to narrow the list down to a set of 50 of these genes that could uniquely identify each type.

These tumor types have been previously defined and are known as luminal A, luminal B, HER2-enriched and basal-like. The latter three types are generally considered types with a poor prognosis. Another genomic test commonly used in clinical practice, OncotypeDX, does not identify all four tumor types.

"Our test is the first to incorporate a molecular profile for the basal-like type breast cancers," says Ellis, professor of medicine in the Division of Medical Oncology at Washington University School of Medicine. "That's important because these breast cancers are arguably the most aggressive yet the most sensitive to chemotherapy. By identifying them we can ensure they are treated adequately."

Breast cancer experts typically also identify a fifth breast cancer type known as normal-like. The 50-gene set also recognizes the normal-like type. But the researchers found that instead of being a fifth type of breast cancer, the normal-like classification is an indicator that a sample contains insufficient tumor cells to make a molecular diagnosis and that a new sample needs to be taken.

In this study, the researchers also compared the activity of the 50-gene set to how well 133 breast cancer patients responded to standard chemotherapy. They found that their genetic test was highly sensitive and very predictive for chemotherapy response. The test was more predictive than typically used clinical molecular markers such as estrogen receptor status, progesterone receptor status or HER2 gene expression status.

They found that luminal A was not sensitive to the chemotherapy, suggesting that patients with this good-prognosis type can forgo chemotherapy in favor of hormone-based therapy. They showed that among the poor-prognosis tumor types, basal-like breast cancer was the most sensitive to the chemotherapy and luminal B the least.

"Luminal B tumors are a very poor prognosis group, and none of the current conventional therapies are particularly effective against it," Ellis says. "The ability to identify luminal B tumors accurately makes it possible to develop better therapies for this type."

Ellis says more than 20 drugs are available to treat breast cancer. The researchers are now investigating how each tumor type responds to these drugs to help determine the best treatment for each. Their 50-gene set can be assayed in preserved tumor samples left over from standard diagnostic procedures, so the group plans to study tumor samples from breast cancer cases going back a decade or more. Since the patients in these cases have already been treated, the researchers can relatively quickly discover how well various therapies worked for each breast cancer type.

The genomic test technology is patented and will be distributed through University Genomics, a company co-owned by Washington University, the University of Utah and the University of North Carolina. This year University Genomics is working with Associated Regional and University Pathologists Inc., a reference laboratory at the University of Utah, to provide a site where the 50-gene test will be available. Ellis is one of the inventors of the test and holds patents for the technology described here.

Funding from the National Cancer Institute, the Breast Cancer Research Foundation, the Susan G. Komen Foundation, the Huntsman Cancer Institute Foundation and the ARUP Institute for Clinical and Experimental Pathology supported this research.

Cancer Death Rates Dropping Among African Americans But Survival Rates Still Low

While death rates from cancer continue to drop among African Americans, the group continues to be diagnosed at more advanced stages and have lower survival rates at each stage of diagnosis compared to whites for most cancer sites.

The findings come from Cancer Facts & Figures for African Americans 2009-2010, the latest edition of a report produced every two years by the American Cancer Society.

The new report says death rates for all cancers combined have decreased faster in African American men than white men, primarily because of rapid declines in the death rates from lung and prostate cancers. While overall cancer death rates have also decreased among African American women, they are dropping at a slower rate than among white women. The slower decline in African American women is largely due to smaller decreases in breast and colorectal cancer death rates.

The report estimates that among African Americans in 2009, there will be about 150,090 new cases of invasive cancer diagnosed and about 63,360 cancer deaths. The most commonly diagnosed cancers among African American men will be prostate (34 percent), lung (16 percent), and colon and rectum (10 percent). Among African American women, the most common cancers will be breast (25 percent), lung (12 percent), and colon and rectum (11 percent). Cancer of the lung will be the most common cause of cancer death in both African American men (31 percent) and women (23 percent), followed by prostate cancer in men (12 percent) and breast cancer in women (19 percent). Cancer of the colon and rectum and cancer of the pancreas are expected to be the third and fourth most common causes of cancer death in both men and women.

"African Americans have the highest death rate of any racial and ethnic group in the U.S. for most cancers," said Otis W. Brawley, M.D., American Cancer Society chief medical officer. "As this report points out, the causes of these disparities are complex and likely reflect social and economic disparities, not biologic differences. African Americans face inequalities in income, education, and standard of living, as well as barriers to accessing high-quality health care. And while it is discouraging that these differences still exist, we absolutely must face them and continue to enact policies to address them in order to save lives and reduce suffering from cancer among African Americans."

Although the overall racial disparity in cancer death rates is decreasing, in 2005, the death rate for all cancers combined continued to be 33 percent higher in African American men and 16 percent higher in African American women than in white men and women, respectively.

Additional statistics in the report include:

• Cancer death rates are lower among more educated African Americans compared to those with less education. However, at each level of education, African Americans have higher death rates than whites.
• According the National Health Interview Survey in 2006, almost half of African American adults reported no leisure-time physical activity compared to 35 percent of whites. Physical activity has been associated with lower risk of cancers of the breast, colon, prostate, and endometrium.
• According to the most recent data (2005-2006) from the National Health and Nutrition Examination Survey, 76 percent of African Americans adults are overweight and 46 percent are obese, compared to 66 percent and 33 percent, respectively, of whites.
• Only half of African American women aged 40 and older reported getting a mammogram within the past year, slightly less than the 53 percent of whites. Forty percent of African Americans reported a recent colorectal cancer screening test in 2005 compared to 50 percent of whites.
• African American boys and girls, among whom smoking rates have been decreasing since the late 1990s, have lower smoking rates than any other racial/ethnic group.

The report also includes highlights of American Cancer Society efforts to save lives and eliminate disparities in cancer morbidity and mortality. In 2006, the American Cancer Society built on a long history of research and programs designed to understand and describe the impact of health disparities, and to implement and advocate for evidence-based strategies to reduce or eliminate them, by launching an ambitious effort to address inequities in cancer prevention services, access to care, incidence, and mortality.

Pediatric Hodgkin's Disease Survivors Face Increased Breast Cancer Risk

Women who as children got radiation treatment for Hodgkin's disease are almost 40 times more likely than others to develop breast cancer, according to findings from five institutions, including the University of Florida.

The higher the radiation dose, the higher the risk, researchers report. These women are also likely to develop cancer in both breasts.

"Our first priority is always to get rid of the cancer. Our second priority is to do so in a way that preserves the best possible quality of life," said researcher Nancy Mendenhall, M.D., an oncologist with UF's College of Medicine who co-authored a paper detailing the results in the September issue of the International Journal of Radiation Oncology Biology Physics. "These findings tell us we're moving in the right direction with recent changes in treatment that lower radiation dose."

In the past, children with Hodgkin's disease were treated with radiation alone, in relatively high doses to large volumes of the body. Today, doses are half the levels used 20 years ago, smaller portions of the body are treated, and, in many cases, radiation has been replaced by chemotherapy.

"One of the hopes of that strategy is not only are there going to be better cure rates for Hodgkin's disease, but also fewer long-term side effects of therapy," said Kenneth B. Roberts, M.D., an associate professor of therapeutic radiology at Yale University who was not involved in the study.

At the start of 2005, there were almost 76,000 women in the United States who had a history of Hodgkin's disease, according to the National Cancer Institute.

Death rates from Hodgkin's disease have plummeted by more than 70 percent in the last 40 years in the United States, and researchers now focus on reducing the so-called "late effects" of treatment that show up long afterward.

"We expect the future to be better than the past in terms of the likelihood of people developing breast cancer," said University of Rochester pediatric oncologist Louis S. Constine, M.D., who led the study. Still, he said, "it's important to understand the past because many people were treated like this."

Similar studies will be needed to measure the success of modern treatment strategies, Roberts said.

Hodgkin's disease is a cancer of unknown cause that affects tissue in the lymph nodes, spleen, liver and bone marrow. It can spread from one organ to another but can be cured with radiation, chemotherapy or a combination.

The American Cancer Society estimated that in 2008, about 8,220 people in the United States would be diagnosed with Hodgkin's disease and about 1,350 would die from it. Up to 15 percent of all cases occur in children and teenagers.

In the current study, 398 females younger than 19 who were treated for Hodgkin's were evaluated from 1960 until 1990. They had been seen at UF, the Rochester Medical Center, Boston Children's Hospital and Dana-Farber Cancer Institute, St. Jude Children's Research Hospital or the Sidney Kimmel Cancer Center at Johns Hopkins University.

Researchers found that women who had been treated for childhood Hodgkin's disease were 37 times more likely than others to develop breast cancer — 29 developed breast cancer during the study's follow-up period.

On average, it took almost 19 years after treatment for cancer to develop. Guidelines call for Hodgkin's survivors to start being monitored for breast cancer 10 years after treatment or at age 30 — whichever comes first.

In the study, patients ages 12 to 19 at the time of treatment were at slightly higher breast cancer risk as adults than those who were younger than 12. And those diagnosed with early-stage Hodgkin's were at higher risk than those with more advanced disease.

Hodgkin's survivors who developed breast cancer were much more likely to have received higher radiation doses to the entire chest and neck — the so-called "mantle field" — which exposes both breasts to radiation.

About one-third of women who developed cancer in one breast also developed another cancer in the opposite breast. The time from the first to the second cancer ranged from one to three years.

"(That) means people need to be screened, if anything, even more intently after the development of the first cancer," Constine said.

Preventive mastectomies for certain patients at high risk for breast cancer might be worth considering, researchers said.

Surprisingly, radiation of the pelvis seemed to lower cancer risk.

"That finding challenges one of our basic beliefs, so I think we have to do a little more work to understand what is happening," Mendenhall said.

Researchers had thought that the greater the volume of tissue irradiated, the greater the cancer risk. But it is possible that radiation to the pelvis caused premature menopause or ovary failure, with an accompanying drop in the production of the hormone estrogen, a known risk factor for breast cancer.

Factors other than radiation treatment — such as biologic predisposition to cancer — could be at play in the observed rates of cancer development, the researchers said. A trait responsible for the development of breast cancer could also be responsible for Hodgkin's disease development in the first place.

Calcium Associated With Lower Risk Of Cancer In Women

Women with higher intake of calcium appear to have a lower risk of cancer overall, and both men and women with high calcium intakes have lower risks of colorectal cancer and other cancers of the digestive system, according to a report in the February 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Calcium is known to benefit bone health, according to background information in the article. Because of this, the Institute of Medicine recommends 1,200 milligrams of calcium for adults age 50 and older, and the 2005 dietary guidelines for Americans recommend 3 cups per day of low-fat or fat-free dairy products. Studies of dairy products, calcium intake and cancer have revealed different results for different cancer sites.

Yikyung Park, Sc.D., of the National Cancer Institute, Bethesda, Md., and colleagues analyzed data from 293,907 men and 198,903 women who participated in the National Institutes of Health-AARP Diet and Health Study. Participants took a food frequency questionnaire when they enrolled in the study between 1995 and 1996, reporting how much and how often they consumed dairy and a wide variety of other foods and whether they took supplements. Their records were then linked with state cancer registries to identify new cases of cancer through 2003.

Over an average of 7 years of follow-up, 36,965 cancer cases were identified in men and 16,605 in women. Calcium intake was not associated with total cancer in men but was in women—the risk decreased in women with intake of up to 1,300 milligrams per day, after which no further risk reduction was observed.

"In both men and women, dairy food and calcium intakes were inversely associated with cancers of the digestive system," the authors write. The one-fifth of men who consumed the most calcium through food and supplements (about 1,530 milligrams per day) had a 16 percent lower risk of these types of cancer than the one-fifth who consumed the least (526 milligrams per day). For women, those in the top one-fifth of calcium consumption (1,881 milligrams per day) had a 23 percent lower risk than those in the bottom one-fifth (494 milligrams per day). The decreased risk was particularly pronounced for colorectal cancer. Calcium and dairy food intake was not associated with prostate cancer, breast cancer or cancer in any other anatomical system besides the digestive system.

"Dairy food, which is relatively high in potentially anticarcinogenic nutrients such as calcium, vitamin D and conjugated linoleic acid, has been postulated to protect against the development of colorectal and breast cancer," the authors write. Calcium has been shown to reduce abnormal growth and induce normal turnover among cells in the gastrointestinal tract and breast. In addition, it binds to bile and fatty acids, potentially reducing damage to the mucous membrane in the large intestine.

"In conclusion, our findings suggest that calcium intake consistent with current recommendations is associated with a lower risk of total cancer in women and cancers of the digestive system, especially colorectal cancer, in both men and women," the authors write.

The study was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.

Metastasis-promoting Protein In Urine Identified; Could Provide A Prognostic Test Or Target For Breast Cancer

Tumors that are about to progress and metastasize go through a process also seen in normal embryonic development, known as the epithelial to mesenchymal transition (EMT). Tumor cells revert to a less-differentiated state, stop adhering to each another and become more mobile and prone to invade and proliferate. Now, researchers at Children's Hospital Boston show, for the first time, that a small protein called lipocalin 2 triggers the EMT in human breast cancer – and that the same protein, when measured in tissues and urine, can predict a cancer's invasiveness.

Their findings were published online February 23 by the Proceedings of the National Academy of Sciences.

Researchers led by Marsha A. Moses, PhD, and Jiang Yang, PhD, of the Vascular Biology Program at Children's, induced human breast cancer cells to make large amounts of lipocalin 2, and showed that cell motility and invasiveness increased significantly. They then took cells from aggressive breast cancers and silenced lipocalin 2, and found that cell migration was significantly inhibited. When they transplanted human breast cancer cells into animals, those from tumors making lipocalin 2 were more locally invasive and more likely to metastasize to lymph nodes.

Further laboratory studies indicated that lipocalin 2 decreases the levels of estrogen receptor alpha, thereby reducing the cells' response to the hormone estrogen, which is associated with poor prognosis of breast cancer. Inhibiting the production of estrogen receptor alpha is also the mechanism that triggers the EMT pathway, the researchers show.

Finally, tissue samples, and even urine samples, from women with invasive breast cancer consistently showed elevated lipocalin 2 levels, suggesting that testing for lipocalin 2 may be a way of detecting cancer progression and the need for more aggressive treatment.

"Our study identifies a novel, additional player in the complex development of invasive breast cancer," says Moses, the Vascular Biology Program's interim director. "It suggests that this protein may represent a prognostic and/or therapeutic target for this devastating disease."

Lipocalin 2, along with other urine biomarkers of cancer identified in Moses's lab, has been licensed to Predictive Biosciences, Inc. (Lexington, Mass.) for clinical development.

The study was funded by the National Institutes of Health, the JoAnn Webb Fund for Angiogenesis Research, the Riehl Family Foundation, the S. Elizabeth O'Brien Trust and the Advanced Medical Foundation.

Concerns Over Minimally Invasive Surgery For Breast Cancer

Minimally invasive breast surgery may be trading better cosmetic outcomes for worse rates of cure, warns a senior doctor in an editorial published on the British Medical Journal website.

Effectiveness and safety, as well as aesthetic outcomes, need to be considered when planning surgery for breast cancer, writes Monica Morrow, Chief of the Breast Service at Memorial Sloan-Kettering Cancer Center in New York. But over the past 30 years, surgery has become increasingly devoted to improving cosmetic outcomes.

New techniques such as oncoplastic and endoscopic surgery, which involve minimal skin incision, are now possible. But a review of the evidence reveals that the oncological safety of these new procedures is often not being evaluated thoroughly.

Morrow is concerned that failure to demand a rigorous evaluation of oncological outcomes as well as cosmetic ones runs the risk of losing some of the gains in survival seen in the past decade.

"We must ensure that surgical approaches designed to improve cosmetic outcomes do not increase local failure and the risk of subsequent death from breast cancer," she says.

She also points out that the developing fields of oncoplastic surgery and minimally invasive breast surgery require rigorous assessment of patient reported outcomes to ensure that new procedures actually improve outcomes that are important to patients.

"The local treatment of breast cancer is based on the results of numerous high quality clinical trials and is therefore a model for evidence based care. As we attempt to advance from good to great cosmetic outcomes it is important that we remember this," she concludes.

Protein Encourages Cell Growth And Migration In Prostate Cancer

Researchers from Thomas Jefferson University have identified a protein that appears to play a significant role in the growth and migration of prostate cancer cells, especially androgen-independent prostate cancer cells. The study was published in the American Journal of Pathology.

They also found that prostate cancer cells express more of the protein when compared to normal prostate cells, according to Andrea Morrione, Ph.D., an associate professor and director of Urology Research for the Kimmel Cancer Center at Jefferson.

Dr. Morrione conducted the study with Leonard Gomella, M.D., chairman of the department of Urology, Raffaele Baffa, M.D., an associate professor in the department of Urology, and Renato V. Iozzo, M.D., Ph.D., professor in the department of Pathology, Anatomy and Cell Biology.

Proepithelin is a growth factor that promotes cell cycle progression and cell growth in many cellular systems. According to Dr. Morrione, the overexpression of proepithelin by prostate cancer cells may prove to be a useful clinical marker to diagnose prostate cancer.

The presence of proepithelin also encourages cell migration, which is necessary for tumor metastasis. Thus, it may serve as a marker for metastasis.

Proepithelin has previously been shown to play a role in the formation of bladder cancer, and its overexpression is related to an aggressive form of breast cancer according to Dr. Morrione. It also has been shown to play a role in many other cancers, including glioblastomas, multiple myeloma, renal cell carcinoma, gastric cancer and ovarian cancer.

"There are two possible implications of our findings," Dr. Morrione said. "First, proepithelin could be a therapeutic target since it is overexpressed in prostate cancers.

Second, the overexpression of proepithelin could serve as a biomarker and be a diagnostic tool for prostate cancer."

Although localized prostate cancers are potentially curable by surgery and/or radiation therapy, there is no uniform effective treatment for hormone-refractory prostate cancer. There are no reliable prognostic markers to identify which of patients are likely to progress to metastatic disease.

Results of this study will also be presented at the 2009 ASCO Genitourinary Cancers Symposium.

Younger Breast Cancer Patients Have Greater Chance Of Recurrence, Especially After Certain Treatments

Breast cancer patients 35 years old and younger have higher rates of their cancer returning after treatment than older women patients with the same stage of cancer, and their risk of recurrence is greatly impacted by the type of treatment they received, according to a March 1 study in the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Radiation Oncology (ASTRO).

Previous studies have shown that younger breast cancer patients consistently have poorer outcomes than patients who develop the disease later in life, which can translate into lower rates of overall survival. While the reason for this is not known, it is suggested that breast cancer in younger patients is more biologically aggressive.

Researchers from the University of Texas M.D. Anderson Cancer Center in Houston sought to determine which form of breast cancer treatment – breast-conserving therapy, mastectomy alone or mastectomy with adjuvant radiation – better benefits younger women with either Stage I or Stage II breast cancer.

A total of 652 young women with breast cancer from 1973 to 2006 were studied, with 197 of the patients having received breast-conserving therapy, 237 having received a mastectomy and 234 having received mastectomy with adjuvant radiation. The study authors confirmed that younger breast cancer patients do have relatively high locoregional recurrence rates, but that patients with Stage II disease achieved the best locoregional control rates with mastectomy plus adjuvant radiation therapy. Patients with Stage I disease had similar outcomes with breast-conserving therapy and mastectomy, but adding chemotherapy to either treatment was beneficial.

“Locoregional recurrence after optimal breast cancer treatment in young women remains a significant problem,” Beth Beadle, M.D., Ph.D., a resident at M. D. Anderson and lead author of the study, said. “Our study hopefully will help radiation oncologists plan therapies for younger breast cancer patients, who have inferior outcomes compared to older patients, and generate new interest in prospective studies to evaluate the best treatment strategies for these young women.”

Women With BRCA Mutation, Or Worry, Most Likely To Undergo Prophylactic Mastectomy

Women at increased risk for breast cancer because of the genetic BRCA mutations are more likely to think a prophylactic mastectomy is the best way to reduce their risk for the disease, compared to other women who are at high risk, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, published in the most recent issue of Cancer, also finds that the emotional worry was a strong factor leading women – both BRCA mutation carriers and others at high risk for the disease – to opt for the surgery.

It's estimated that .1 to .2 percent of the general population carry either the BRCA 1 or 2 mutation, both of which are associated with an increased risk of breast and/or ovarian cancer. For those with the BRCA1 mutation, their lifetime risk of developing breast cancer is 47-66 percent, with some estimates even higher; those with BRCA2 have a lifetime risk of 40-57 percent.

Women are referred to genetic counseling because of a personal diagnosis of breast cancer at a very young age, or a strong family history of the breast and/or ovarian, explained Jennifer Litton, M.D., assistant professor in M. D. Anderson's Department of Breast Medical Oncology.

"Women who are even suspected to have a BRCA mutation are highly motivated and need to make important decisions regarding their treatment options, even if they don't have cancer," said Litton the study's senior author. "With the study, we wanted to determine the reasons why women make different choices in either screening - including breast-self exams, mammograms, or MRIs – or prophylactic measures, such as medications like Tamoxifen or surgeries."

In conducting the study, the researchers sent surveys to 540 women who received genetic counseling and were screened for the BRCA mutations at M. D. Anderson between 1997 and 2005. Of those surveys, 312 (58 percent) were returned: 217 (70 percent) had breast cancer and 86 (28 percent) tested positive for the BRCA1 or 2 mutation.

In the surveys, patients were asked questions regarding their fear of developing the disease, as well as their feelings on: the screening techniques mammograms and breast-self exams; the drug Tamoxifen and its known side effects, and prophylactic surgeries.

Regarding mammograms and self breast exams, the study found little difference between the BRCA positive and negative cohorts. Neither group felt that mammograms were too difficult to get because of discomfort, nor did either report being too embarrassed to perform breast-self exams. In addition, there was no statistical difference in the two groups' feelings toward Tamoxifen: 37.9 percent of the BRCA positive patients and 46.5 percent of the BRCA negative patients felt that the concerns associated with the drug outweighed its benefits for reducing risk of developing breast cancer.

In evaluating the response to questions regarding prophylactic mastectomies, the researchers began to see significant differences between the two groups, and "worry" as a recurring concern.

When comparing BRCA positive to BRCA negative cohorts: 70 percent versus 40 percent respectively felt that prophylactic mastectomies were the most effective way to reduce their risk of developing the disease; 36.1 percent versus 40.5 percent respectively felt it was too drastic of a measure to prevent breast cancer; 23.9 percent versus 12.5 percent respectively had difficulty in deciding between surgery and screening.

Regarding their degree of worry, 64.7 percent of BRCA positive patients thought a prophylactic mastectomy was the only way to reduce their fear of the disease, compared to 34.4 percent of BRCA negative patients.

When combining both groups, after excluding women with bilateral breast cancer, 81 percent who thought surgery was their best way to reduce their risk, and 84 percent of those who felt that it was their best way to reduce their worry ultimately underwent the procedure. In contrast, 19.1 percent of those who did not feel that the surgery was the best way to reduce their risk and 15.8 percent of women who did not think it was their only way to decrease their worry opted to have a prophylactic mastectomy.

In her clinical experience, Litton has seen many high-risk women, particularly those who test positive for the BRCA 1 or 2 mutation, that initially opt for intensive screening, but after several mammograms, MRIs and biopsies, eventually decide to have a prophylactic mastectomy.

"For clinicians, this study shows that when we're counseling women about prophylactic mastectomies, we need to not just talk about the surgery, but understand their lifestyles," said Litton. "When the worry of developing cancer is interfering with a patient's day-to-day activities, then their quality of life is impacted. These women with a high risk of developing breast cancer may find that despite the surgery and subsequent recuperation, a prophylactic mastectomy improves their quality of life."

Women at highest risk need to ask themselves some very important, personal questions that only they have the answers to, said Litton.

"When making such a personal decision, these women at highest risk need to ask themselves about how they feel about their breast as far as their body image, sexuality, relationship with and support of their partner, as well as their concern for breast cancer. If that worry comes in the way of their day-to-day activities, it should be taken into consideration as part of the patient's decision-making process."

Litton cautioned that the results should not be generalized for the majority of the breast cancer population. Additionally, high risk women, of course, should also be counseled on the risk associated with surgery.

As a follow up to this study, Litton plans to conduct a study with high-risk women of child-bearing age pre- and post-genetic counseling to determine their degree worry, their guilt of possibly passing on the gene to their offspring and thoughts on pre-gestational diagnosis.

The study was funded in part by the Nellie B. Connally Breast Cancer Research Fund and a grant from the National Institutes of Health.

In addition to Litton, other authors on the all-M. D. Anderson study include: Gabriel Hortobagyi, M.D., Banu Arun, M.D., Ana Gonzalez-Angulo, M.D., Kaylene Ready, all of the Department of Breast Medical Oncology; Karen Lu, M.D., Diane Bodurka, M.D., Charlotte Sun, DRPH, Shannon Westin, M.D., all of the Department of Gynecologic Oncology; Funda Meric-Bernstam, M.D., Department of Surgery; and Susan Peterson, Ph.D., Department of Behavioral Science.