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.

Systematic Estimation Of Breast Cancer Risk Appears Justified In Postmenopausal Women

Screening for breast cancer risk in all postmenopausal women, using a combination of risk factors and breast density, can identify women at high risk of disease, according to systematic literature reviews and meta-analyses reported in the March 10 online issue of the Journal of the National Cancer Institute.

The reviews and meta-analyses also support the use of chemoprevention in women at high risk of disease and the value of positive lifestyle changes in all women irrespective of their breast cancer risk.

Although models have been developed to estimate a postmenopausal woman's risk of breast cancer, it has not been clear whether the routine use of the models in clinical practice is supported by clinical trial data.

To determine whether regular screening for the risk of breast cancer was justified, Steven Cummings, M.D., of the San Francisco Coordinating Center at the California Pacific Medical Center Research Institute in San Francisco, and colleagues used systematic literature reviews and conducted meta-analyses of clinical trials that examined the predictive accuracy of risk assessment models and breast density measurement to identify women at high risk of disease. They also reviewed prospective studies that examined the impact of lifestyle factors on breast cancer risk, and they conducted a meta-analysis of clinical trials with tamoxifen and raloxifene for primary prevention of breast cancer.

The researchers found that risk assessment models that were based on demographic characteristics and medical history alone had moderate ability to discriminate women's risk of breast cancer. However, accuracy improved when the models were combined with breast density information. A meta-analysis supported the efficacy of either tamoxifen or raloxifene for primary prevention of breast cancer. Finally, a systematic review and meta-analysis also found that exercise, weight reduction, low-fat diet, and reduced alcohol intake may reduce a woman's risk of breast cancer.

"In conclusion, evidence from these reviews supports systematic assessment of postmenopausal women for breast cancer risk with risk factors and assessment of breast density. Chemoprevention should be considered for those at high risk; however, cost-benefit analyses are needed to provide specific recommendations about who should be offered chemoprevention," the authors write. "Several lifestyle changes can be recommended to postmenopausal women, regardless of their estimated risk category."

Should Breast Tissue Be Screened For Cancer After Cosmetic Surgery?

Young women undergoing cosmetic breast reduction surgery are being screened for cancer without their informed consent, according to a paper published on the British Medical Journal website.

Breast reduction surgery (mammoplasty) is one of the most common procedures performed by plastic surgeons all around the world. For decades it has been common practice to test the removed tissue for cancer.

The incidence of cancer found after surgery is small and often clinically insignificant. But, if found, it can lead to further surgery of unproven benefit. So should the current practice of routinely testing tissue after surgery be abandoned, or should doctors discuss this issue in advance with the patient and ensure that they are aware of the possible consequences?

A team of breast surgeons based at the Royal Free Hampstead NHS Trust and Royal Free and University College Medical School in London describe finding cancer after a routine cosmetic operation on a 37 year old woman. The discovery led to a succession of further operations, but the team question the ethics of acting on test results when there is no evidence for benefit.

They also point out that it is often not possible to identify exactly where in the breast the tissue came from because tissue specimens are not orientated during surgery.

In an accompanying commentary, Tom Treasure, a Professor of Cardiothoracic Surgery at University College London suggests that the question of what is the best management of a patient with these findings in the future remains unanswered. "Not putting the tissue under the microscope may seem unacceptable," he writes, "but so is continuing surgical practices that may result in harm, without having evidence of benefit."

In a second commentary, ethicist Jeremy Sugarman suggests that even though the likelihood of the specimens being malignant is small, discussing this issue in advance should help to prepare patients to receive the news and to face the complex decisions that follow. He believes that this matter warrants careful, expert review. In the meantime, he suggests that obtaining informed consent for screening and orientating these specimens should help to mitigate some of the difficult ethical issues that are encountered in practice.

Like any potential patient, I welcome any procedures made to safeguard my health and would appreciate being informed of every aspect (and associated risk) of an operation. I would not appreciate being left in the dark, writes Tessa Boase, in a final commentary. She believes that the current practice of screening of breast tissue after reduction mammoplasty should be maintained and perhaps refined, but the patient should, from start to finish, be kept in the loop. "Who else, after all, is this screening supposed to benefit?" she says.

Red Wine Vs. White? Both Equal Offenders In Breast-cancer Risk

The largest study of its kind to evaluate the effect of red versus white wine on breast-cancer risk concludes that both are equal offenders when it comes to increasing breast-cancer risk. The results of the study, led by researchers at Fred Hutchinson Cancer Research Center, were published in the March issue of Cancer Epidemiology, Biomarkers and Prevention.We were interested in teasing out red wine's effects on breast-cancer risk. There is reason to suspect that red wine might have beneficial effects based on previous studies of heart disease and prostate cancer," said lead author Polly Newcomb, Ph.D., M.P.H., head of the Cancer Prevention Program in the Public Health Sciences Division at the Hutchinson Center. "The general evidence is that alcohol consumption overall increases breast-cancer risk, but the other studies made us wonder whether red wine might in fact have some positive value."

Instead, Newcomb and colleagues found no compelling reason to choose Chianti over Chardonnay.

"We found no difference between red or white wine in relation to breast-cancer risk. Neither appears to have any benefits," Newcomb said. "If a woman drinks, she should do so in moderation – no more than one drink a day. And if a woman chooses red wine, she should do so because she likes the taste, not because she thinks it may reduce her risk of breast cancer," she said.

The researchers found that women who consumed 14 or more drinks per week, regardless of the type (wine, liquor or beer), faced a 24 percent increase in breast cancer compared with non-drinkers.

For the study, the researchers interviewed 6,327 women with breast cancer and 7,558 age-matched controls about their frequency of alcohol consumption (red wine, white wine, liquor and beer) and other breast-cancer risk factors, such as age at first pregnancy, family history of breast cancer and postmenopausal hormone use. The study participants, ages 20 to 69, were from Wisconsin, Massachusetts and New Hampshire. The frequency of alcohol consumption was similar in both groups, and equal proportions of women in both groups reported consuming red and white wine.

The National Cancer Institute, a branch of the National Institutes of Health, funded this research, which also involved investigators from Group Health Cooperative, Seattle; the University of Wisconsin; H. Lee Moffitt Cancer Center & Research Institute; and Dartmouth Medical School.

High Blood Pressure Linked To Earlier Death Among African-American Breast Cancer Patients

A study by researchers at the University of California, San Francisco has shown that hypertension, or high blood pressure, is a predictor of mortality among breast cancer patients, especially those who are African-American, and that hypertension accounts for approximately 30 percent of the survival disparity between African-American and white breast cancer patients.

According to the study’s lead author, UCSF epidemiologist Dejana Braithwaite, PhD, of the UCSF Helen Diller Family Comprehensive Cancer Center, who also is an affiliate with the UCSF National Center of Excellence in Women’s Health, this is the first study to link cancer mortality with hypertension, and specifically the first to show that hypertension is a predictor of mortality among African-American breast cancer patients.

“White women are more likely to get breast cancer, but African-American women are more likely to die from it,” said Braithwaite. “We were trying to shed light on the factors that contribute to disparities in survival between the two groups.”

The study included 416 African-American and 838 white women diagnosed with breast cancer between 1973 and 1986, following them through 1999. All of the women in the study were patients at Kaiser Permanente in Northern California. The patients were all residents of the San Francisco Bay Area and had a known stage of disease and course of cancer treatment.

Kaiser Permanente members are representative of the general population for many ethnic, demographic and socioeconomic categories, except for the very high and very low ends of the economic spectrum, according to the study. The researchers used data from patient records, which theyconsidered more reliable than data self-reported by patients. Kaiser Permanente’s division of research has long collaborated with UCSF on breast cancer research.

The study found that African-American breast cancer patients had a higher overall crude mortality, or death from all causes, than whites during the study period: 39.7 percent versus 33.3 percent respectively over a mean follow-up of nine years.

When age, race, tumor characteristics, and breast cancer treatment were controlled, hypertension accounted for 30 percent of the racial disparity in mortality, study findings showed.

“High blood pressure led to poorer outcomes for African-American patients than for their white counterparts,” said Braithwaite. “Even if you statistically control for tumor characteristics and breast cancer treatments—chemotherapy, surgery, radiation, and hormone treatment—the adverse effect of hypertension in African-American women means a greater likelihood of death.”

Hypertension is not part of the Charlson Comorbidity Index, a widely-used generic tool that provides survival estimates for patients using a range of co-existing conditions or so-called comorbidities. If the results of this study are validated in more contemporary patient populations, the research suggests that hypertension should be included in this Index because of its high predictive value for outcomes, said Braithwaite.

According to study senior author Laura Esserman, MD, director, Carol Franc Buck Breast Care Center; co-leader, Breast Oncology Program, UCSF Helen Diller Family Comprehensive Cancer Center; and part of the UCSF National Center of Excellence in Women’s Health, comorbidities have a huge influence on life expectancy and therefore influence treatment decisions for breast cancer. “We started out by trying to determine which comorbidities should be assessed for all patients routinely, and discovered that hypertension in African-Americans is associated with higher mortality from breast cancer,” she said.

In addition, this information may provide clues to the cause of higher mortality in African American women with breast cancer, Esserman said.

“The message is that hypertension is a big deal. It affects African-Americans more than other ethnic groups, and it affects their survival overall. Better management of hypertension has potential to improve patient outcomes, particularly among African-American breast cancer patients,” Braithwaite concluded.

Co-authors of the study with Braithwaite and Esserman are Jeff Belkora, PhD; Dan Moore, PhD, and Robert Hiatt, MD, PhD, all of UCSF; C. Martin Tammemagi, PhD, Brock University, Ontario, Canada; Elissa Ozanne, PhD, Massachusetts General Hospital, Boston; Dee West, PhD, Northern California Cancer Center, Fremont, Calif.; William Satariano, PhD, UC-Berkeley; and Michael Liebman, PhD, Windber Research Institute, Windber, Penn.

The study was funded by the Windber Research Institute;Kaiser Permanente’s Community Benefit Program and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute; and U.S. Department of Defense, Center of Excellence in Breast Cancer Care, principal investigator Laura Esserman.

Twin Nanoparticle Shown Effective At Targeting, Killing Breast Cancer Cells

Breast cancer patients face many horrors, including those that arise when fighting the cancer itself. Medications given during chemotherapy can have wicked side effects, including vomiting, dizziness, anemia and hair loss. These side effects occur because medications released into the body target healthy cells as well as tumor cells.

The trick becomes how to deliver cancer-fighting drugs directly to the tumor cells. Brown University chemists think they have an answer: They have created a twin nanoparticle that specifically targets the Her-2-positive tumor cell, a type of malignant cell that affects up to 30 percent of breast cancer patients.

The combination nanoparticle binds to the Her-2 tumor cell and unloads the cancer-fighting drug cisplatin directly into the infected cell. The result: Greater success at killing the cancer while minimizing the anti-cancer drug's side effects.

"Like a missile, you don't want the anti-cancer drugs to explode everywhere," explained Shouheng Sun, a chemistry professor at Brown University and an author on the paper published online in The Journal of the American Chemical Society. "You want it to target the tumor cells and not the healthy ones."

The researchers created the twin nanoparticle by binding one gold (Au) nanoparticle with an iron-oxide (Fe3O4) nanoparticle. On one end, they attached a synthetic protein antibody to the iron-oxide nanoparticle. On the other end, they attached cisplatin to the gold nanoparticle. Visually, the whole contraption looks like an elongated dumbbell, but it may be better to think of it as a vehicle, equipped with a very good GPS system, that is ferrying a very important passenger.

In this case, the GPS comes from the iron-oxide nanoparticle, which homes in on a Her-2 breast-cancer cell like a guided missile. The attached antibody is critical, because it binds to the antigen, a protein located on the surface on the malignant cell. Put another way, the nanoparticle vehicle "docks" on the tumor cell when the antibody and the antigen become connected. Once docked, the vehicle unloads its "passenger," the cisplatin, into the malignant cell.

"It's like a magic bullet," said Chenjie Xu, a Brown graduate student and the lead author on the paper. Baodui Wang, a visiting scientist at Brown and now an associate professor at Lanzhou University in China, contributed to the paper.

In a neat twist, the Brown-led team used a pH-sensitive covalent bond to connect the gold nanoparticle with the cisplatin to ensure that the drug was not released into the body but remained attached to the nanoparticle until it was time for it to be released into the malignant cell.

In laboratory tests, the gold-iron oxide nanoparticle combination successfully targeted the cancer cells and released the anti-cancer drugs into the malignant cells, killing the cells in up to 80 percent of cases. "We made a Mercedes Benz now," Sun joked. "It's not a Honda Civic anymore."

The research builds on previous work in Sun's lab where researchers created peptide-coated iron-oxide nanoparticles that, in tests with mice, successfully located a brain tumor cell called U87MG.

The researchers will test the breast-cancer nanoparticle system in laboratory tests with animals. They also plan to create twin nanoparticles that can release the drug via remote-controlled magnetic heating.

The breast-cancer nanoparticle research was funded by the National Institutes of Health.

Obese Women Play Cancer Roulette

Obese women may be putting themselves at greater risk of breast cancer by not undergoing regular screening. According to new research by Dr. Nisa Maruthur and her team from The John Hopkins University School of Medicine in Baltimore, USA, seriously obese women are significantly less likely to say they have undergone a recent mammography than normal weight women, especially if they are white.

Breast cancer is the second leading cause of cancer death among women in the US. Mammography screening has been proven to reduce the number of deaths from breast cancer; current guidelines recommend that women over the age of 40 undergo a mammography every couple of years. Obesity is also an important risk factor for both the development of, and death from, postmenopausal breast cancer.

Maruthur and colleagues conducted a systematic review and meta-analysis of 17 studies comprising over 276,000 participants, to look at whether overweight and obese women are less likely to have had a recent mammography than normal weight women. They also looked at the differences in mammography take-up between white and black obese women in three of the studies. They found that severely obese women were 20 percent less likely to have had a recent mammography than normal weight women. However, this was not the case among black women.

The authors highlight a number of reasons why obese women may not be undergoing breast cancer screening, including a delay in taking up medical care because of poor self-esteem and body image, embarrassment, a perceived lack of respect from their health care providers and unwanted weight loss advice. According to the authors, obesity may be a marker for sub-optimal health behavior in general, of which mammography is simply one element. The authors also suggest that there are racial differences in obesity-related body image which may explain the difference in take-up of mammography between white and black women.

The authors conclude that “the main implication of our study is that a lack of routine screening mammography may explain some of the increased breast cancer mortality in obese postmenopausal women. Clinicians should be aware of this disparity in evaluating their own practices.”

Small Molecules Block Cancer Gene

Finding molecules that block the activity of the oncogene Stat3 (signal transducer and activator of transcription) required screening literally millions of compounds, using computers that compared the structure of the cancer-causing gene to those of the small molecules, said a Baylor College of Medicine researcher in a report that appears in the current online issue of the journal PLoS One.

It was worth the effort, said Dr. David J. Tweardy, professor of medicine and molecular and cellular biology and chief of the division of infectious diseases at BCM, because it could point the way to better treatment of breast and other cancers, as well as chronic viral infections, asthma, and inflammatory bowel disease. He is also on the faculty of the NCI-designated Dan L. Duncan Cancer Center at BCM.

Virtual screening

The "virtual" high throughput screening looked at the possibility of "docking" 920,000 small drug-like compounds into a pocket of a specific domain of Stat3, said Tweardy. In other words, Tweardy and his colleagues identified an area on the Stat3 molecule that was important to its activity. Stat3 actually is critical in keeping malignant cells alive in the majority of cancers.

Once Tweardy and his colleagues had identified a critical "pocket" on Stat3, they used the computer to look for small molecules that would fit in that pocket and block the ability of Stat3 to maintain the cancer cell. That screen of nearly 1 million small molecules identified three likely compounds.

Assays of these compounds showed that they did halt the activity of Stat3 in the laboratory. With that information, Tweardy and his colleagues then screened another 2.47 million compounds for similarity to the original three.

They found another three. While five of the six had some activity in stopping Stat3, one – called 188 – was most effective. Three of the six worked to induce programmed cell death or apoptosis in breast cancer cell lines.

"It induced death in those breast cancer cells that depend for their survival on Stat3," said Tweardy.

Second-generation compounds

Tweardy and his colleagues are now looking at second generation compounds that promise to be even more effective against Stat3.

When he and his colleagues started looking at Stat3, they knew it was important in cancers of the head and neck. Further research showed that it also was important in breast, lung and prostate cancers as well as multiple myeloma (a cancer affecting blood-forming cells) and acute myelogenous leukemia.

Stat3 also plays a role in chronic virus infections, asthma, psoriasis and inflammatory bowel disease – all areas that Tweardy and his colleagues hope to pursue in the future.

Others who took part in this research include Xuejun Xu, Moses M. Kasembeli, Xueqing Jiang and Benjamin J. Tweardy, all of BCM.

Funding for this research comes from the National Cancer Institute.

Early Detection Of Second Breast Cancers Halves Women’s Risk Of Death

A group of international researchers has found the first reliable evidence that early detection of subsequent breast tumours in women who have already had the disease can halve the women’s chances of death from breast cancer.

According to the research published online in the cancer journal Annals of Oncology, if the second breast cancer was picked up at its early, asymptomatic stage, then the women’s chances of survival were improved by between 27-47% compared to women whose second breast cancer was detected at a later stage when symptoms had started to appear.

Until now, the impact of early detection of second breast cancers was unclear. Attempts to investigate it have been complicated by the fact that it is not possible to run randomised controlled trials because women who have already had one breast cancer are at higher risk of a relapse or a second breast cancer and, therefore, are generally advised to have regular breast checks as part of their follow-up care. What studies there have been have not made adjustments for the main factors that could bias the findings from a non-randomised study and often have looked at breast cancers occurring in either the same breast (ipsilateral relapse) or the other breast (contralateral) but not either breast.

The current study looked at 1,044 women who had attended one clinical centre in Florence (Italy) between 1980-2005 and who had developed a second breast cancer. In that time 455 women had ipsilateral breast cancers (IBC) diagnosed and 589 women had contralateral breast cancers (CBC) diagnosed. Of these second cancers, 699 (67%) were asymptomatic and 345 (33%) were symptomatic.

The researchers found that mammography was more sensitive than clinical examination for detecting second cancers (86% versus 57%). However, 13.8% of cases were only detected by clinical examination. Asymptomatic cancers were smaller than symptomatic for both IBC and CBC; early stage cancers were more frequent in asymptomatic (58.1%) than in symptomatic (22.6%) women; and fewer women with asymptomatic than symptomatic CBC had node metastases (an indicator that the cancer may have spread).

In the analysis of the results, the researchers (from Italy, Australia and the UK) adjusted to allow for lead-time bias (bias caused by an earlier detection of the cancer) and length-time bias (bias caused by the fact that some breast cancers develop more slowly than others and, therefore, are more likely to be detected at the asymptomatic stage and are less likely to cause death).

Associate Professor Nehmat Houssami, a breast physician and principle research fellow at the University of Sydney’s School of Public Health, Australia, who led the study, said: “Intuitively, it makes sense to consider that early detection of second breast cancers will improve prognosis, since breast cancer survivors have a long-term risk of developing further disease or relapse in either breast. However, due to a paucity of evidence about this until now, current recommendations on surveillance of breast cancer survivors vary substantially between countries and organisations.

“Our study provides new evidence on several aspects of early detection of second breast cancers. We set out to estimate the effect of early, asymptomatic detection while adjusting for the two main biases known to be associated with non-randomised studies of the impact of early detection – lead time and length bias – so we believe that the estimates we report are more valid than previously reported estimates, while acknowledging the limitation that the evidence is not from a randomised controlled trial.

“In addition, we have estimated this for early detection of either ipsilateral or contralateral breast cancer, while other studies have focused on one or the other. So our estimates may be more useful for clinicians discussing this aspect of breast cancer follow-up with their patients.”

She continued: “To our knowledge, this is the only study to have taken length-time bias into account when quantifying the impact of early, asymptomatic detection of breast cancer. This is important because slow-growing or indolent cancers have a much smaller probability of proving fatal, and this group of women will tend to be over-represented in the early-detected cancers, biasing the effect of screening to make it appear more beneficial.”

In their paper, the researchers write: “Recommendations on follow-up after treatment of early breast cancer should consider our findings, which suggest that early detection of second breast cancer events improves prognosis in this ever-increasing group of women.”

Prof Houssami said: “Periodic surveillance of women with BC is currently under scrutiny in some countries and questions have been raised as to the value of sustained follow-up of breast cancer survivors in some health settings. So I think this work provides a timely reminder of the potential benefit of early detection of second breast cancers and supports ongoing surveillance in this group of women.”

She said that their finding that nearly 14% of second breast cancers were only detected by clinical examination and that mammograms had a sensitivity of 86% was also important. “There are health settings where new imaging (ultrasound or MRI) is advocated for screening because of the belief that mammography is not sufficient and misses too many cancers in breast cancer survivors. Our data suggest that mammography, with clinical examination, is sensitive and effective (with the caveat that the Florence centre where the study originated has established experience in mammography of at least 40 years). We feel that additional screening imaging should only be used selectively, for example, in women with extremely dense breasts, or when investigating questionable findings from the mammogram or clinical examination.”

Prof Houssami concluded: “The next step is to determine how to maximise early detection in this specific setting while ensuring feasibility and efficiency. One possibility currently under exploration would be to estimate the risk of a symptomatic tumour and the stage of the symptomatic tumour by time since the last mammogram. There are many questions about the optimal process and model of surveillance, such as frequency for surveillance and who should be performing longer-term surveillance in breast cancer patients, that we have not addressed in this study. These issues require further research.”

Racial Disparities In Cancer Mortality Rates Between Blacks And Whites Quantified

African Americans have a shorter life expectancy than whites, and cancer plays a major role in this disparity. African Americans are more prone to get cancer; they tend to present at a later, deadlier stage; and they have poorer survival rates after diagnosis.

But to what extent are each of these three factors responsible for the disparity in cancer mortality? A new UCLA study, published in Journal of General Internal Medicine Feb. 18, answers that question, finding that for most types of cancer, the disparity in mortality is almost entirely due to the fact that African Americans are more likely to get cancer in the first place. Their stage at presentation and survival after diagnosis play a much smaller role.

Overall, African American men live 1.47 fewer years than white men, and African American women 0.91 fewer years than white women, due to all cancers combined. The results spotlight the need for greater prevention efforts aimed at African Americans.

This is the first time that researchers have quantified the role that disparities in cancer incidence, stage at diagnosis and survival after cancer plays in African Americans' shorter life expectancy, according to lead author Dr. Mitchell D. Wong, associate professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA.

"Putting a number on it is very informative, because when you look at the figures, you see that the reason their mortality is worse is almost entirely due to the fact that blacks are more likely to get cancer," Wong said. "This highlights the importance of prevention — it's where most of the efforts should be."

A notable exception to this pattern was breast cancer. While white women are more likely to get breast cancer than African American women, the disparities between whites and blacks in stage at presentation and survival after diagnosis for breast cancer had a large impact on the racial gap in life expectancy.

"This argues for much more research and efforts to close the gap in breast cancer screening and treatment," Wong said.

The researchers analyzed data from the Surveillance and Epidemiology End Result (SEER) cancer registry and the National Health Interview Survey (NHIS). Together, the data sets covered about 2.7 million white and 291,000 African American cancer patients from 12 geographic regions in the United States: San Francisco/Oakland, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle (Puget Sound), Utah, Atlanta, Alaska, San Jose/Monterey and Los Angeles.

Among the other findings:

• Cancer incidence, stage at diagnosis and post-diagnosis survival accounted for 1.12, 0.17 and 0.21 years, respectively, in the life-expectancy disparity among men.
• Among women, those categories accounted for 0.41, 0.26 and 0.31 years, respectively.
• The difference in incidence of cancer had a greater impact on the racial gap in cancer mortality than did the stage at which the cancer was diagnosed.
• The differences in post-diagnosis survival were significant with only two types of cancer: breast (0.14 years) and prostate (0.05 years).

"Continuing to improve cancer treatment and screening is undoubtedly important to improving life expectancy and quality of life for all adults, yet substantial disparities in cancer mortality will persist unless we can find ways to address the enormous impact of racial differences in cancer incidence," the researchers concluded.

In addition to Wong, study authors included Susan L. Ettner and Martin F. Shapiro of the David Geffen School of Medicine at UCLA, and John Boscardin of the division of geriatrics at the San Francisco Veterans Administration Medical Center.

The National Institute on Aging, the National Center on Minority Health and Health Disparities, a Pfizer Scholars Grant in Clinical Epidemiology, and a Doris Duke Charitable Foundation Clinical Scientist Development Award funded this study.

Quality Of Life May Impact Coping Strategies Of Young Women With Breast Cancer

Numerous studies have shown a relationship between coping strategies and quality of life (QOL) among women with breast cancer. In a study published March 24 in the online edition of Journal of Behavioral Medicine, an investigation of coping strategies and quality of life among younger women with breast cancer suggests that QOL determines the use of coping strategies.It is generally assumed that coping strategies impact quality of life, with more active coping strategies generally associated with better QOL," said Suzanne C. Danhauer, Ph.D., assistant professor at Wake Forest University Baptist Medical Center and lead investigator of these analyses. This investigation was part of a study focused on younger women with breast cancer conducted by co-author and Principal Investigator Nancy E. Avis, Ph.D. The study was funded by the National Cancer Institute. "This research examined coping strategies over time and the reciprocal relationship between coping strategies and QOL among younger women with breast cancer to see if the opposite might be true -- that QOL determines the use of coping strategies," said Danhauer.

Studies have consistently shown that younger women report greater psychological distress following breast cancer diagnosis than older women. Several investigations have also found that younger women with breast cancer report significantly worse QOL than older women, particularly in emotional and social domains.

From a developmental perspective, younger women face unique issues such as premature onset of menopause that may lead to infertility, sudden onset of vasomotor symptoms (hot flashes and/or night sweats) and long-term consequences of ovarian decline; changes in relationships with one's partner and/or children; multiple role demands of parenthood and career, and greater concerns about body image and sexuality.

Participants in the study, "A Longitudinal Investigation of Coping Strategies and Quality of Life among Younger Women with Breast Cancer," consisted of 267 women with breast cancer, with a mean age of 43 years, who completed baseline surveys within six months of diagnosis and follow-up surveys six weeks and six months later. The surveys included questions on coping strategies, QOL and medical factors.

Eligible women were sent a baseline packet of self-report questionnaires to complete. Following completion of the baseline survey, women were randomly assigned to receive a booklet or videotape describing how women often respond to a breast cancer diagnosis. Follow-up surveys were completed within six to eight weeks and six to eight months after the mailing of the educational material. These time frames were selected to assess short- and longer-term impact of the interventions.

Results of the study revealed that coping strategies in younger women changed over time. Seeking social support, spirituality, wishful thinking, and making changes decreased over time and detachment increased. Positive cognitive restructuring (reinterpreting something stressful as positive or helpful) was the most frequently used coping strategy and its use remained high over time. Keeping feelings to oneself was the least used coping strategy and its use remained consistently low over time.

Despite the unique issues and difficulties experienced by younger women with breast cancer, their coping strategies do not appear different from those of women with breast cancer in general regardless of age.

The reciprocal relationship between QOL and coping strategies during the year following diagnosis showed an interesting pattern. Coping at one time point showed little predictive value of subsequent QOL. However, poorer QOL was a significant predictor of greater use of several coping strategies (seeking social support, keeping feelings to self and wishful thinking) at subsequent time points. This finding suggests that people adapt their coping strategies in response to problems with which they are dealing.

While the study had several limitations (e.g. sample comprised predominantly of higher educated Caucasian women and only younger women), it adds a valuable contribution to the literature on coping with cancer.

"We emphasize, however, that this finding is suggestive and not definitive," Danhauer said. "The relationship between coping strategies and QOL is complicated and future studies should examine this reciprocal relationship."

Risk Of Aggressive Breast Cancer Subtype Three Times Higher For Black Women

Lifestyle, age and weight have all been considered as risk factors for breast cancer. A new study has found that even taking these factors into consideration, black women face three times the risk of developing an aggressive 'triple negative tumour' compared to women of other racial backgrounds.

In the US, which has the highest rate of breast cancer in the world, the overall incidence of breast cancer is lower in black women than in white women. Yet when black women do get breast cancer, it tends to be more advanced when diagnosed, has a higher risk or recurring and a less favourable outcome.

A research team led by Dr Carol Rosenberg at Boston University School of Medicine searched hospital records from the Boston Medical Center, focusing on 415 breast cancer cases. The team looked at clinical features particularly patient age, weight and race/ethnicity, and pathological features including the triple-negative pattern - tumours that lack expression of the estrogen receptor, the progesterone receptor and the HER2 gene

According to Rosenberg, "The odds of having a triple negative tumour were three times higher for black women than for non-black women in the study. Previously, it was known that pre-menopausal black women had more triple negative tumors. What we found that was new was that these tumours were just as common in black women diagnosed before or after age 50, and in those who were or were not obese."

Rosenberg adds, "The higher prevalence of triple negative breast tumours in black women in all age and weight categories likely contributes to black women's unfavourable breast cancer prognosis."

Eating Soy Early In Life May Reduce Breast Cancer Among Asian Women

Asian-American women who ate higher amounts of soy during childhood had a 58 percent reduced risk of breast cancer, according to a study published in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.Historically, breast cancer incidence rates have been four to seven times higher among white women in the U.S. than in women in China or Japan. However, when Asian women migrate to the U.S., their breast cancer risk rises over several generations and reaches that of U.S. white women, suggesting that modifiable factors, rather than genetics, are responsible for the international differences. These lifestyle or environmental factors remain elusive; our study was designed to identify them," said Regina Ziegler, Ph.D., M.P.H., a senior investigator in the NCI Division of Cancer Epidemiology and Genetics (DCEG).

The current study focused on women of Chinese, Japanese and Filipino descent who were living in San Francisco, Oakland, Los Angeles or Hawaii. Researchers interviewed 597 women with breast cancer and 966 healthy women. If the women had mothers living in the United States, researchers interviewed those mothers to determine the frequency of soy consumption in childhood.

Researchers divided soy intake into thirds and compared the highest and lowest groups. High intake of soy in childhood was associated with a 58 percent reduction in breast cancer. A high level of soy intake in the adolescent and adult years was associated with a 20 to 25 percent reduction. The childhood relationship held in all three races and all three study sites, and in women with and without a family history of breast cancer. "Since the effects of childhood soy intake could not be explained by measures other than Asian lifestyle during childhood or adult life, early soy intake might itself be protective," said the study's lead investigator, Larissa Korde, M.D., M.P.H., a staff clinician at the NCI's Clinical Genetics Branch.

"Childhood soy intake was significantly associated with reduced breast cancer risk in our study, suggesting that the timing of soy intake may be especially critical," said Korde. The underlying mechanism is not known. Korde said her study suggests that early soy intake may have a biological role in breast cancer prevention. "Soy isoflavones have estrogenic properties that may cause changes in breast tissue. Animal models suggest that ingestion of soy may result in earlier maturation of breast tissue and increased resistance to carcinogens."

As provocative as the findings are, Ziegler cautioned that it would be premature to recommend changes in childhood diet. "This is the first study to evaluate childhood soy intake and subsequent breast cancer risk, and this one result is not enough for a public health recommendation," she said. "The findings need to be replicated through additional research."

Bioengineered Proteins: Trial Confirms New Way To Tackle Cancer

Re-engineering a protein that helps prevent tumours spreading and growing has created a potentially powerful therapy for people with many different types of cancer. In a study published in the first issue of EMBO Molecular Medicine, Canadian researchers modified the tumour inhibiting protein, von Hippel-Lindau (VHL), and demonstrated that it could suppress tumour growth in mice.

When solid tumours grow they often have relatively poor and disorganised blood supplies. As a result, various regions including the centre of the tumour have low levels of oxygen and are said to be hypoxic. Cells in these hypoxic areas produce hypoxia-inducible factor (HIF) that helps them carry on growing. Consequently HIF is associated with aggressiveness in some of the most common types of cancer, including prostate, breast, colon and lung cancer. Under normal conditions VHL degrades HIF, but VHL is deactivated when oxygen levels are low. So, in hypoxic regions of a tumour, just where VHL is needed to inhibit cancer, it is ineffective.

The researchers, therefore, created a new version of VHL that does not stop working when oxygen is scarce. Introducing this newly engineered version of VHL into mice that had kidney tumours dramatically reduced levels of HIF, caused tumours to regress and limited the formation of new blood vessels within the tumours.

"We have genetically removed the Achilles' heel of VHL to permit unrestricted destruction of HIF," says lead researcher Professor Michael Ohh, who works in the Faculty of Medicine at the University of Toronto. "The level of HIF is usually very high under conditions of low oxygen, but when we put in our bioengineered VHL its levels go right down to a level that would be comparable to that in normal oxygen levels."

Their findings could have implications for any type of cancer in which HIF plays a role. "We used kidney cancer as a model because it is one of the most resistant tumours to conventional radiation and chemotherapy, but our findings provide a novel concept that could potentially serve as a foundation for smarter anti-cancer strategy for a wide variety of cancers," says Ohh.

Biopsy Of Recurrent Breast Cancer Can Alter Treatment

For women with recurrent breast cancer, the treatment the doctor chooses is usually based on the properties of their original breast cancer. A group from Toronto has recently completed the world's first study that compared original breast cancer tumors with a biopsy of suspected tumors that recurred elsewhere in the body.

Researchers found that the biopsy resulted in 20% of the women having a significant change in their treatment. In some cases, this was a change in drug treatment and in others, the biopsy showed the woman did not actually have an advanced cancer, but a benign condition.

"The results show that cancers may change over time and not respond to treatment that was appropriate for the original cancer," says principal investigator Dr. Mark Clemons, a medical oncologist specializing in breast cancer in the Princess Margaret Hospital Cancer Program, University Health Network (UHN).

"These early findings are leading us in a new direction as we understand more about why some women don't respond to treatment. This knowledge will help us in our quest to always deliver the right treatment, to the right patient, at the right time."

Dr. Clemons's study -- funded by a $100,000 research grant from the Canadian Breast Cancer Foundation - Ontario Region -- evaluated 29 biopsies of accessible, recurrent tumors taken from women whose breast cancer had spread to bone, skin, lymph nodes, lung or liver.

Pathologists compared the results of the original cancer with the results of the new biopsy by analyzing the predictive markers that influence breast cancer tumor growth – estrogen, progesterone and Her2 status. The presence, absence and/or combinations of these markers become the map oncologists use to determine the most effective treatment for each patient.

In 15 cases, the diagnosis was unchanged; in 10 cases the markers in the cancer changed; in three cases, women originally felt to have metastatic breast cancer had benign disease, and in one case, the "recurring" cancer was a different type of cancer, lymphoma which is treated in a very different way to breast cancer.

Co-author Dr. Christine Simmons says: "For some of the women in the study, the findings dramatically altered their treatment and made a big difference in their lives."

Study participant Danielle Lee couldn't agree more. Two years ago, the then 30-year-old mother of a toddler and eight-month-old was coping with a diagnosis that her breast cancer had spread to her spine. The results of the new biopsy confirmed that there was no cancer in her spine.

New Test May Predict Breast Cancer Metastasis

Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have identified a new marker for breast cancer metastasis called TMEM, for Tumor Microenvironment of Metastasis. As reported in the March 24 online edition of the journal Clinical Cancer Research, density of TMEM was associated with the development of distant organ metastasis via the bloodstream — the most common cause of death from breast cancer.

The National Cancer Institute (NCI)–funded translational study could lead to the first test to predict the likelihood of breast cancer metastasis via the bloodstream — a development that could change the way breast cancer is treated.

An estimated 40 percent of breast cancer patients relapse and develop metastatic disease. About 40,000 women die of metastatic breast cancer every year.

"Currently, anyone with a breast cancer diagnosis fears the worst — that the cancer will spread and threaten their lives. A tissue test for metastatic risk could alleviate those worries, and prevent toxic and costly measures like radiation and chemotherapy," says senior author Dr. Joan G. Jones, professor of clinical pathology and laboratory medicine at Weill Cornell Medical College and director of Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

"If patients can be better classified as either low risk or high risk for metastasis, therapies can be custom tailored to patients, preventing over-treatment or under-treatment of the disease," adds first author Dr. Brian D. Robinson, resident in Anatomic Pathology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The Weill Cornell investigators set out to build on previous research by co-author Dr. John S. Condeelis of the Albert Einstein College of Medicine. Working in animal models, he identified a link between blood-borne or systemic metastasis and a three-part association between invasive carcinoma cells, perivascular white blood cells (macrophages) and the endothelial cells that line vessel walls. To confirm this finding in humans, Drs. Jones and Robinson developed a triple immunostain for human breast cancer samples that simultaneously labels the three cell types that together they named TMEM (Tumor Microenvironment of Metastasis).

In a case-control study, they performed a retrospective analysis of tissue samples from 30 patients with invasive ductal carcinoma of the breast who developed systemic, distant-organ metastases. These samples were compared to matched controls that had only localized disease (i.e., invasive ductal carcinoma limited to the breast or with regional lymph node metastasis only). All patients were female and underwent primary resection of their breast cancer at NewYork-Presbyterian Hospital/Weill Cornell Medical Center between 1992 and 2003.

They found that TMEM density was more than double in the group of patients who developed systemic metastases compared with the patients with only localized breast cancer (median of 105 vs. 50, respectively). Offering further evidence in support of the TMEM concept, they found that in well-differentiated tumors, where the outcome is generally good, the TMEM count was low.

Notably, TMEM density was associated with the development of distant-organ metastasis, independent of lymph node status and tumor grade.

"Traditionally, the likelihood of breast cancer metastasis is estimated based on tumor size, tumor differentiation — how similar or dissimilar the tumor is compared to normal breast tissue — and whether it has spread to the lymph nodes. While these are useful measures, TMEM density directly reflects the blood-borne mechanism of metastasis, and therefore may prove to be more specific and directly relevant," says Dr. Jones.

The researchers say the next step will be to validate the findings in a larger sample group. Also on the agenda is identifying a threshold TMEM density for metastasis risk, and streamlining the process for measuring TMEM.

Breast cancer is the most prevalent malignant disease of women in the developed world, apart from non-melanoma skin cancers, with approximately one in eight women in the United States being diagnosed with breast cancer at some time in their lives. While an estimated 10 percent to 15 percent of patients have an aggressive form of the disease that metastasizes within three years after initial diagnosis, metastasis can take 10 years or longer to occur. To decrease the risk for the emergence of metastatic tumors, approximately 80 percent of breast cancer patients are treated with adjuvant chemotherapy. The clinical benefit is a 3 percent to 10 percent increase in 15-year survival, depending upon the age of the patient at diagnosis.

Study co-authors include Drs. Gabriel L. Sica and Yi-Fang Liu of NewYork-Presbyterian/Weill Cornell; Dr. Thomas E. Rohan of the Department of Epidemiology and Population Health at Albert Einstein College of Medicine; Dr. Frank B. Gertler of the Department of Biology, Koch Institute for Integrative Cancer Biology at Massachusetts Institute of Technology; and Dr. John S. Condeelis of the Department of Anatomy & Structural Biology, Program in Tumor Microenvironment and Metastasis, Albert Einstein Cancer Center at the Albert Einstein College of Medicine.

The study was funded by the Integrative Cancer Biology Program (ICBP) of the National Cancer Institute (NCI).

Light Reveals Breast Tumor Oxygen Status

Light directed at a breast tumor through a needle can provide pathologists with biological specifics of the tumor and help oncologists choose treatment options that would be most effective for that individual patient.

Duke University bioengineers have developed a light-based system that can quickly and easily provide important information about oxygen levels within a tumor while it is still in place. The new system, based on diffuse reflectance spectroscopy, gives researchers important clues about the tumor by interpreting how the light is either reflected back from the tumor or absorbed.

Oxygen status is important, the researchers said, since past studies have shown that low levels of oxygen, or hypoxia, are more often associated with malignant tissue than healthy normal tissue. Tumors that thrive in these low-oxygen environments tend to be more difficult to treat, the researchers said.

"We developed an easy-to-use fiber-optic probe that can provide immediate and non-destructive measurements of tumor oxygenation," said J. Quincy Brown, a fourth-year post-doctoral fellow in the laboratory of Nirmala Ramanujam, associate professor of biomedical engineering at Duke's Pratt School of Engineering. The results of the Duke experiments were published April 1 in the journal Cancer Research.

"This new approach could be an important new tool for physicians in determining the aggressiveness of a specific tumor and which therapies might work best against it," Brown said. "Since this system is compatible with commonly used biopsy needles, we could make oxygen measurements at the time of a needle biopsy, providing immediate feedback about the tumor's oxygen concentration."

In their current experiments, the researchers enrolled 35 women who were to undergo surgery for their breast cancer. Before the surgery, the researchers directed normal, UV-visible light directly through a needle at the surface of the tumor while it was still in the breast. Since the system gathers information immediately, researchers are able to take readings at multiple locations in little time.

Their main target was blood and its hemoglobin, a protein which is responsible for carrying oxygen throughout the body, as well as to tumors. While some types of breast cancer thrive in environments low in oxygen, other cancers stimulate the growth of new blood vessels to feed oxygen to the tumor.

"Our system measured how the light was either absorbed by the hemoglobin, which gave us an optical fingerprint of the oxygen status of the tumor," Brown explained. "This fingerprint can give clues about which form of therapy – chemo, radiation, surgery – might be the most effective for that particular tumor."

One interesting finding involved tumors with the gene HER2/neu. It is estimated that one in five breast cancers exhibit over-expression of the HER2/neu gene. A routinely used drug known as Herceptin, which can block HER2/neu over-expression, is only effective in treating tumors with this gene.

"The tumors that over-expressed the HER2/neu gene had significantly higher levels of oxygen," Brown said. "This is likely due to the fact that the amplification of this gene encourages the formation of tiny new blood vessels, which in turn feed the tumor. Knowing how the Her2/neu status of a tumor is affecting tumor oxygenation at the time of biopsy would be useful information for the oncologist, since over-expression of this gene typically leads to a cancer that is more aggressive and more resistant to treatment."

The researchers plan future studies of breast cancer patients undergoing chemotherapy by taking regular oxygen measurements to determine how a particular tumor is responding to therapy over time.

The research was supported by National Institutes of Health and the Duke Comprehensive Cancer Center. Other Duke members of the research team were Lee Wilke, Joseph Geradts, Stephanie Kennedy and Gregory Palmer.

Protein That May Help Breast Cancer Spread, Beat Cancer Drugs, Identified

New research from UC Davis Cancer Center shows that a protein called Muc4 may be the essential ingredient that allows breast cancer to spread to other organs and resist therapeutic treatment. The study, which appears in the April 1 issue of Cancer Research, is one of the first to characterize the role of Muc4 in the disease.

Kermit Carraway, senior author of the study, knew that Muc4 was not always expressed in primary breast cancer tumors, yet it could be present in lymph node metastases. He suspected that it may have a specialized function in the process of metastasis.

"Breast cancer deaths are caused by metastasis, not by the primary tumor," explained Carraway, an associate professor of biochemistry and molecular medicine. "It's at that point that the disease also becomes difficult to treat. We think that Muc4 may be packing a one-two punch by promoting the release of breast cancer cells from the primary tumor and then inhibiting their death."

Muc4 is member of a group of proteins called mucins, which are commonly found in fluids such as tears and mucus. They have a known role in protecting epithelial cells, from which breast cancer cells are derived. When separated from their surrounding cell matrix, epithelial cells tend to die. Metastasizing breast cancer cells, however, can survive this detachment.

"Because breast cancer cells can lose their adhesive properties and still thrive, we suspected that Muc4 may be somehow allowing them to leave their cellular framework, travel to secondary sites and withstand treatment," Carraway explained.

To test his suspicions, Carraway and his team conducted two experiments. They started by comparing breast cancer cells that express Muc4 with those for which Muc4 production is blocked. The researchers then exposed both types of cells to chemotherapy drugs. The Muc4-producing cells survived.

They repeated the experiment with breast cancer cells and epithelial cells that do not naturally express Muc4 but were engineered to do so. Both sets of cells avoided cell death and effectively resisted chemotherapy.

"Our results lead us to believe that Muc4 is somehow disrupting normal links between epithelial cells," said UC Davis graduate student Heather Workman, lead author of the study. "We now need to refine our understanding of this disruption process in order to find ways to interfere with it. There currently are no drugs that target Muc4, and this research will help change that."

Carraway is now preparing to test metastasizing breast cancer tumor cells for the overexpression of Muc4.

"If we find that Muc4 is all over metastasizing breast cancer cells, it will confirm that we are on the right track," he said.

While Carraway's current focus is on breast cancer, his findings could have relevance to other cancers that show aggressive properties. For example, Muc4 is also expressed in pancreatic, lung and ovarian tumor cells.

"Muc4 is likely a central cellular mechanism for metastasis of many cancers, and we will be continuing this important work to prove that," he said.

Joining Carraway and Workman on the research team was Colleen Sweeney, a UC Davis associate professor of biochemistry and molecular medicine. The study was funded by individual grants to each of the three authors from the National Institutes of Health.

Breast Cancer: To Screen Or Not To Screen?

Women are often told that mammography saves lives. But rarely is the question asked, 'how often?' Researchers set out to examine how often this life-saving event occurs.

Unrealistic expectations may influence a woman's decision whether or not to participate in screening mammography. Over 90% of women think that 'early detection saves lives'. John D Keen and James E Keen, of the John H. Stroger Jr. Hospital of Cook County and the University of Nebraska, respectively, aimed to promote informed decision-making by calculating the age-dependent absolute benefit of screening in three traditional ways: the absolute risk reduction from repeated screening, the number of women needed to screen repeatedly to save one life, and the survival percentages with and without mammography. They also estimated the average benefit of a single mammogram. Their novel concept of life-saving proportion is also relevant to economic analyses of screening.

They found that the life-saving benefit of mammography gradually increases with age along with the screen-free absolute death risk, which is about 1% over 15 years starting at age 55. The corresponding risk of developing breast cancer is about 6%. Repeated screening starting at age 50 saves about 1.8 lives over 15 years for every 1000 women screened. The average benefit of a single screening mammogram is 0.034%; in other words, 2970 women must be screened once to save one life. Alternatively, twenty-three cancers must be detected. Assuming a base case 20% relative risk reduction, the survival percentage in younger women at age 40 is 99.52% without and 99.62% with screening, meaning that there is a 0.1% increased chance of survival with screening than without it.

According to the authors, "We have assumed that a 'life saved' means screening helps cure one woman with breast cancer who would otherwise have died from the disease without screening ... However, all women with breast cancer may theoretically benefit from screening mammography through slowing the disease and therefore slightly prolonging their lives".

"For a woman in the screening subset of mammography-detectable cancers, there is a less than 5% chance that a mammogram will save her life. By comparing mammography's life-saving absolute benefit with its expected harms, a well-informed woman along with her physician can make a reasonable decision to screen or not to screen for breast cancer."

As this research article is highly controversial, BMC Medical Informatics and Decision Making has provided two commentaries from experts in the field. Dr Stephen Duffy of Cancer Research UK argues that direct results from empirical data might be more trustworthy than modelled estimates derived by combining data from disparate sources. On the other hand, Dr Michael Retsky from the Harvard Medical School praises this study, noting that it is a positive step in the right direction considering that too often women aged 40-49 are asked to sign informed consent for mammography without being properly informed of the potential risks.

Gene May Lead To Early Onset Of Brain Tumor

People with a particular gene variant may be more likely to develop brain tumors, and at an earlier age, than people without the gene, according to a study published in the January 27, 2009, print issue of Neurology®, the medical journal of the American Academy of Neurology.

The study involved 254 people with brain tumors and 238 people with no cancers. All those with tumors had glioblastoma multiforme, the most common type of brain cancer. People with this type of tumor survive an average of 12 to 15 months.

Through blood samples, researchers looked at the tumor suppressor TP53 gene. This gene acts as a tumor suppressor and is involved in preventing cancer.

People younger than 45 with brain tumors were more likely to have the Pro/Pro variant of the gene than older people with brain tumors or the healthy participants. A total of 20.6 percent of the young people with brain tumors had the gene variant, compared to 6.4 percent of the older people with brain tumors and 5.9 percent of the healthy participants.

"Eventually we may be able to use this knowledge to help identify people who have a higher risk of developing brain tumors at an early age. However the risk of this population remains low, even multiplied by three or four as shown here, because these brain tumors (glioblastomas) are infrequent in young people," said study author Marc Sanson, MD, PhD, of the French National Institute of Health and Medical Research (INSERM) in Paris, France.

The study was supported by the Public Assistance Hospitals of Paris.