USPSTF supports counseling, BRCA tests for at-risk women 

28 dec 2013—Nine of 10 women do not need and should not receive genetic testing to see if they are at risk for breast or ovarian cancer, an influential panel of health experts announced Monday.

The U.S. Preventive Services Task Force (USPSTF) reaffirmed its previous recommendation from 2005 that only a limited number of women with a family history of breast cancer be tested for mutations in the BRCA1 and BRCA2 genes that can increase their cancer risk.

Even then, these women should discuss the test with both their family doctor and a genetic counselor before proceeding with the BRCA genetic test, the panel said.

"Not all people who have positive family histories should be tested. It's not at all simple or straightforward," said Dr. Virginia Moyer, the task force's chair.

Interest among women in genetic testing for breast cancer has greatly increased, partially due to Hollywood film star Angelina Jolie's announcement in May that she underwent a double mastectomy because she carried the BRCA1 mutation.

A Harris Interactive/HealthDay poll conducted a few months after Jolie's announcement found as many as 6 million women in the United States planned to get medical advice about having a preventive mastectomy or ovary removal because of the actress' personal decision.

On average, mutations of the BRCA genes can increase breast cancer risk between 45 percent to 65 percent, according to the American Cancer Society.

The problem is that there are myriad mutations of the BRCA gene. Doctors have identified some mutations that increase breast cancer risk, but there are many more BRCA mutations where the increased risk is either low or as yet unknown.

"The test is not something that comes back positive or negative. The test comes back a whole lot of different ways, and that has to be interpreted," Moyer said. "There are a variety of mutations. Often you get what appears to be a negative test but we call it an 'uninformative' negative because it just doesn't tell you anything. A woman would walk away from that with no idea, but worried, and that's not helpful."

Earlier this month, the genetic testing company 23andMe announced it's no longer offering health information with its home-based kit service after the U.S. Food and Drug Administration warned that the test is a medical device that requires government approval.

The new task force recommendations will be published online Dec. 23 in the Annals of Internal Medicine.

The task force's judgment carries heavy weight within the health care industry. For instance, the federal government's list of preventive health care measures that insurers must provide free of charge under the Affordable Care Act is based on USPSTF recommendations.

According to the task force, about 90 percent of American women do not have a family history associated with an increased risk for BRCA mutations, and even fewer will have a mutation that could lead to breast cancer.

"Only two or three women in a thousand have these mutations. Doing this is not going to prevent most breast cancers," Moyer said.

Medical experts are concerned that many women will undergo unnecessary surgery following an unclear genetic test, having their breasts or ovaries needlessly removed to prevent a cancer risk they never had.

"All of us have a copy of the BRCA gene, and some of us have a mutation," said Dr. Otis Brawley, chief medical officer of the American Cancer Society. "Some mutations increase the risk of breast cancer by up to 85 percent, others by 40 percent, others by 10 percent."

"But the woman who now knows she has a mutation is very frightened and very upset, and no amount of explaining that it's of little to no significance will help," Brawley continued.

Both Brawley and Moyer emphasized that any woman interested in BRCA screening should meet with a certified genetic counselor before proceeding. The counselor will take a very detailed clinical history of the patient and assess whether they would benefit from the test.

"The key here is that women who think they might want the test should talk to a genetic counselor, and that genetic counselor should explain the risks and benefits of the test and help them make the decision," Brawley said. "A physician shouldn't necessarily be the person doing it. It should be a certified genetic counselor. Most doctors are not skilled at doing this."

The task force is an independent, volunteer panel of national experts in prevention and evidence-based medicine. It routinely issues recommendations about clinical preventive services such as screenings, counseling services and preventive medications.

More information: Full Text - Evidence Review
Full Text - Recommendation Statement

Angelina Jolie's preventive mastectomy raised awareness, but not knowledge of breast cancer risk

Angelina Jolie heightened awareness about breast cancer when she announced in a New York Times op-ed that she had undergone a preventive double mastectomy. But a new study led by researchers in the University of Maryland School of Public Health and the Johns Hopkins School of Public Health reveals that widespread awareness of Jolie's story did not unfortunately translate into increased understanding of breast cancer risk.

27 dec 2013--The survey of more than 2,500 Americans found that three out of four were aware of Jolie's story, but fewer than 10% of those could correctly answer questions about the BRCA gene mutation that Jolie carries and the typical person's risk of developing breast cancer. Though very rare, women with harmful mutations in either of two genes, BRCA1 and BRCA2, have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal. The study is published today in Genetics in Medicine.

"Ms. Jolie's health story was prominently featured throughout the media and was a chance to mobilize health communicators and educators to teach about the nuanced issues around genetic testing, risk, and prophylactic surgery," explained lead author Dina Borzekowski, who is a research professor in the University of Maryland School of Public Health's Department of Behavior and Community Health. "It feels like it was a missed opportunity to educate the public about a complex but rare health situation."

Among survey respondents who were aware of Jolie's story, nearly half could recall her estimated risk of breast cancer before the surgery, but fewer than 10 percent of those had the necessary information to interpret the risk of an average woman without a BRCA gene mutation relative to Jolie's risk. Additionally, exposure to Jolie's story was associated with greater confusion, rather than clarity, about the relationship between a family history of cancer and increased cancer risk. About half incorrectly thought that a lack of family history of cancer was associated with a lower than average personal risk of cancer, and among respondents who had at least one close relative affected by cancer, those who were aware of Jolie's story were less likely than those who were unaware of her story to estimate their own cancer risk as higher than average (39 vs. 59 percent).

"Since many more women without a family history develop breast cancer each year than those with, it is important that women don't feel falsely reassured by a negative family history," said Dr. Debra Roter, co-author of the study and Director of the Center for Genomic Literacy and Communication at the Johns Hopkins Bloomberg School of Public Health.

Breast cancer cases linked to a BRCA gene mutation are extremely rare, and the average woman's risk of getting breast cancer over her lifetime if she does not have a BRCA mutation is between five and 15 percent.

Other survey findings included that more than half of the women (57%) who had heard the story said they would undergo similar surgery if they carried the faulty BRCA gene, and a majority (72%) of men and women surveyed felt Ms. Jolie did the right thing by publically announcing her situation.

The study concluded that despite the ability of celebrities to raise awareness of health issues by sharing personal stories, these messages need to be accompanied by a more purposeful communication effort to assist the public in understanding and using the complex diagnostic and treatment information that these stories convey.

Provided by University of Maryland

What is BRCA1? 

American actress Angelina Jolie has had a double mastectomy because she carries the faulty gene BRCA1.

Actress Angelina Jolie has today written an op-ed in the New York Times explaining that she has opted to have a double mastectomy because she carries the hereditary BRCA1 gene, which she says increases her risk of breast cancer by 87%. Her mother died from cancer after a ten-year struggle at the age of 56.

15 may 2013--We asked an expert in breast cancer and genetics to explain more about the breast cancer genetic mutation and what it means for women.

What are the BRCA1 (and BRCA2) gene mutations?

BRCA1 and BRCA2 are genes that have been linked to hereditary breast and ovarian cancer. Women who inherit one of these faulty genes are at an increased risk of breast or ovarian cancer. Men who inherit a faulty gene may be at increased risk of prostate cancer. Breast cancer in men carrying BRCA2 has also been described in the medical literature.

These genes are important in helping repair breaks in the DNA in our cells, so a faulty gene can mean that DNA repair is less than optimal. In some people this can lead to the development of cancer.

Should I be getting tested for them?

Not routinely. In general terms, genetic testing should be carried out following counselling in a familial cancer centre after a proper assessment of risk.

Testing is offered to people who have developed breast or ovarian cancer where there are features that might suggest a mutation is present.

These can include an early age of onset of cancer, or cancer in both breasts, multiple cancers in the family, male breast cancer, ovarian cancer, certain ancestry (such eastern European Jewish ancestry), or where there is a known mutation in the family.

Sometimes the appearance of a tumour, reported by the pathologist can help make a decision regarding whether testing is necessary.

How are they tested for?

This is generally done through a blood sample.

What is the cost of the test/s and why?

At present testing for these genes in Australia is expensive – about A$2,000 to A$2,500 – but costs are coming down.

Once a mutation has been identified in a family member, other members can be tested and this is much cheaper.

In Australia, the test is offered for free in familial cancer centres where a person meets suitable criteria for testing.

How many people are affected?

About 5% of all breast cancers are hereditary, and can involve the BRCA1 or BRCA2 gene. That is why it is important to look for special features that suggest risk.

In our community the risk of carrying a gene is relatively rare at about 1:800 for each of the mutations.

Say I have the gene/s, what is the likelihood that I will develop (a) breast cancer and (b) ovarian cancer?

Having the gene does not mean that a woman will definitely develop either of the cancers.

The risk is believed to be on average somewhere between 40% and 65% for breast and 15% to 40% for ovary, depending on the gene.

In her op-ed, Angelina Jolie said her risk of developing breast cancer was 87% and that she had a 50% risk of developing ovarian cancer. This is because the risk for BRCA1 carriers can be higher than for BRCA2 carriers.

Jolie has reported the upper end of risk for breast cancer that was first described when the gene was discovered. Looking at the general population, the risk is probably less, but for some families with very striking family histories, it could be this high.

What are the treatment options?

If a cancer develops, it is often treated in a very similar fashion to other breast or ovarian cancers.

For breast cancer, sometimes women might consider more extensive surgery (such as mastectomies). There are new drugs called PARP inhibitors that are being developed tested for BRCA-associated cancers.

What are the prevention options?

There are a number of options. For breast cancer, this includes close monitoring which includes MRI scans and mammograms starting at a suitable age.

Breast cancer prevention drugs such as Tamoxifen are likely to be helpful and may even halve the risk of getting breast cancer.

Some women may consider mastectomy with breast reconstruction. The uptake of this option differs; on average about 20% of women carrying the genes take this option in Australia but the precise numbers are not known.

Importantly, due to the potential risk of ovarian cancer some women will be advised to have their fallopian tubes and ovaries removed at a suitable age (and after they have had children).

If this is carried out at age 40, it can halve breast cancer risk. It is known to be safe to give women hormone replacement therapy in most cases, so that they don't experience menopausal symptoms.

What are the side-effects of mastectomies, if any?

These are generally minimal. In the short term, there can be surgical risks of infection and bleeding and, of course, cosmetic results (breast reconstruction) may differ.

What are the chances of survival for preventative measures vs treatment options?

The chances of survival for preventative measures are excellent and the risk of breast cancer is very substantially reduced. Since screening can detect cancer early, this helps improve outcomes.

Treatment for breast cancer has substantially improved over the last two decades, including for BRCA1 and BRCA2-associated cancers, so with proper treatment of early cancers, the outlook can be very good.

Source: The Conversation

This story is published courtesy of The Conversation (under Creative Commons-Attribution/No derivatives).

Scientists find new breast cancer genes, rewrite rulebook

Scientists at the BC Cancer Agency and University of British Columbia have identified new breast cancer genes that could change the way the disease is diagnosed and form the basis of next-generation treatments.

20 april 2012--Researchers have reclassified the disease into 10 completely new categories based on the genetic fingerprint of a tumour. Many of these genes could offer much-needed insight into breast cancer biology, allowing doctors to predict whether a tumour will respond to a particular treatment. Whether the tumour is likely to spread to other parts of the body or if it is likely to return following treatment.

The study, published online today in the international journal Nature, is the largest global study of breast cancer tissue ever performed and the culmination of decades of research into the disease.

In the future, this information could be used by doctors to better tailor treatment to the individual patient.

"This is a major step forward in building the genetic encyclopedia of breast cancer and in the process we've learned there are many more subtypes of breast cancer than we imagined. The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most." said Dr. Sam Aparicio, study co-lead author. "The size of this study is unprecedented and provides insights into the disease such as the role of immune response, which will stimulate other avenues of research.

The team at the BC Cancer Agency, in collaboration with Cancer Research UK's Cambridge Research Institute and Manitoba Institute of Cell Biology at University of Manitoba, analyzed the DNA and RNA of 2,000 tumour samples taken from women diagnosed with breast cancer between five and 10 years ago. The sheer number of tumours mapped allowed researchers to spot new patterns in the data.

Study milestones include:

• Classified breast cancer into 10 subtypes grouped by common genetic features, which correlate with survival. This new classification could change the way drugs are tailored to treat women with breast cancer.
• Discovered several completely new genes that had never before been linked to breast cancer. These genes that drive the disease are all targets for new drugs that may be developed. This information will be available to scientists worldwide to boost drug discovery and development.
• Revealed the relationship between these genes and known cell signaling pathways – networks that control cell growth and division. This could pinpoint how these gene faults cause cancer, by disrupting important cell processes.

This is the second major breakthrough announced by BC Cancer Agency scientists in as many weeks. On April 4, a team led by Dr. Sam Aparicio celebrated the decoding of the genetic makeup of the most-deadly of breast cancers, triple-negative breast cancer, which until then was defined by what it was missing, not what it was. Similar to that announcement, today's new discovery identifies genes that were previously unknown to be linked to breast cancer and makes it clear that breast cancer is an umbrella term for what really is a number of unique diseases.

While the research is unlikely to benefit women who currently have breast cancer, it substantially advances how scientists approach further research and clinical trials by providing them with a springboard to develop new treatment options and drugs targeted to specific genes.

More information: "The integrative genomic and transcriptomic architecture of 2000 breast tumours." Curtis et al. Nature. DOI: 10.1038/nature10983

Provided by University of British Columbia

Limited lymph node removal for certain breast cancer does not appear to result in poorer survival

Among patients with early-stage breast cancer that had spread to a nearby lymph node and who received treatment that included lumpectomy and radiation therapy, women who just had the sentinel lymph node removed (the first lymph node to which cancer is likely to spread from the primary tumor) did not have worse survival than women who had more extensive axillary lymph node dissection (surgery to remove lymph nodes found in the armpit), according to a study in the February 9 issue of JAMA.

11 feb 2011--Axillary lymph node dissection (ALND) has been part of breast cancer surgery since the use of radical mastectomy and reliably identifies nodal metastases. "Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection [removal] affects survival," the authors write. "ALND, as a means for achieving local disease control, carries an indisputable and often unacceptable risk of complications such as seroma [a mass or swelling caused by the localized accumulation of serum within a tissue or organ], infection, and lymphedema [condition in which excess fluid called lymph collects in tissues and causes swelling]."

Armando E. Giuliano, M.D., of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, Calif., and colleagues conducted a study to determine the effects of ALND on overall survival in patients with SLN metastases treated with lumpectomy (surgical removal of a tumor without removing much of the surrounding tissue or lymph nodes) and radiation therapy. The trial was conducted at 115 sites and enrolled patients from May 1999 to December 2004. Patients were women with T1-T2 (stage of tumor) invasive breast cancer, no palpable adenopathy (enlarged lymph nodes), and 1 to 2 SLNs containing metastases.

Patients with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Of 891 patients, 445 were randomly assigned to the ALND group and 446 to the SLND-alone group.

As expected, there was a difference between ALND and SLND-alone treatment groups in total number of removed lymph nodes and total number of tumor-involved nodes; the median (midpoint) total number of nodes removed was 17 in the ALND group and 2 in the SLND-alone group. At a median follow-up of 6.3 years, there were 94 deaths (SLND-alone group, 42; ALND group, 52). The use of SLND alone compared with ALND did not appear to result in statistically inferior survival, with the 5-year over all survival rates being 92.5 percent in the SLND-alone group and 91.8 percent in the ALND group. Disease-free survival did not differ significantly between treatment groups, with 5-year disease-free survival being 83.9 percent for the SLND-alone group and 82.2 percent for the ALND group.

The rate of wound infections, axillary seromas, and paresthesias (prickly, tingling sensations) among patients in the trial was higher for the ALND group than for the SLND-alone group (70 percent vs. 25 percent).

The authors note that these results suggest that breast cancer patients, such as those in this study, do not benefit from the addition of ALND in terms of local control, disease-free survival, or overall survival, and that ALND may no longer be justified for certain patients. "Implementation of this practice change would improve clinical outcomes in thousands of women each year by reducing the complications associated with ALND and improving quality of life with no diminution in survival."

More information: JAMA. 2011;305[6]:569-575.

Provided by JAMA and Archives Journals

Hormone therapy begun at menopause may pose risk for breast cancer

Starting hormone therapy at around the time of menopause is associated with a greater risk of breast cancer compared to starting after a longer gap, according to a study published online Jan. 28 in The Journal of the National Cancer Institute.

In this large, prospectively followed cohort of women, those who started hormone therapy five years or more after menopause had little or no increased risk, regardless of the type of hormone therapy used, how long they used it, and whether they were overweight or obese.

30 jan 2011--Many studies have established that breast cancer incidence increases in users of hormonal therapy, in particular among women who use an estrogen-progestin combination as opposed to estrogen-alone. Few studies have looked at the timing of hormone therapy as a risk factor, although two previous studies suggested the interval between menopause and initiating hormone therapy may influence breast cancer risk.

To investigate this question, Valerie Beral, FRS, of Oxford University and colleagues, used data from the Million Women Study (MWS) in the UK. The researchers estimated the adjusted relative risks of breast cancer in hormone therapy users and past users compared to non-users in 1.13 million women in the study. They also compared women on different types of hormone therapy.

They found that women starting hormone therapy at the time of menopause were at greater risk of breast cancer than those starting it later. They write, "A new finding of this study, which has been little investigated previously, is that the interval between menopause and starting hormonal therapy has a substantial effect on breast cancer risk."

Two previous studies have suggested this association but only in certain subgroups. "In this large study, we found greater risks of breast cancer if hormonal therapy use began either before or soon after menopause than after a longer gap; and this pattern of risk was seen across different types of hormonal therapy, among women who used hormonal therapy for either short of long durations, and also in lean and in overweight and obese women."

In an accompanying editorial, Rowan T. Chlebowski, M.D., Ph.D., of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet Anderson from the Fred Hutchinson Cancer Research Center note the study provides substantial support for similar findings from the Women's Health Initiative (WHI) in the U.S. They add that the similarities between the patterns of breast cancer risk in these two large studies increase the likely validity of the results, especially since the methodologies of the two studies were quite different.

The editorialists also discuss discrepancies in the two studies' findings regarding the risk of estrogen-only hormone therapy; the WHI found little risk associated with estrogen alone while the MWS found a statistically significant increased risk, except in overweight and obese women. They conclude that "the question of the effect of estrogen-only formulation use on breast cancer risk in postmenopausal women, even with longer-term hormone use, still stands unanswered."

Provided by Journal of the National Cancer Institute

New findings offer more complete view of breast cancer gene mutations in US population

NIH-supported study among the first to include African Americans, older women

BETHESDA, Md., 04 june 2009-– A large study funded by the National Institutes of Health today provided the clearest picture yet of the prevalence in the U.S. population of mutations in two genes associated with an increased risk of breast cancer. The genes are called Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2). In addition, the study identified key predictors for assessing which women are most likely to carry these genetic mutations.

Each year, approximately 200,000 women in the United States are diagnosed with breast cancer. The majority of breast cancer cases are caused by genetic changes that occur during a woman's lifetime and not by genetic mutations inherited from her parents. However, researchers estimate that inherited mutations play a role in anywhere from 5 to 27 percent of all breast cancer cases. In the mid 1990s, researchers found that mutations in the BRCA1 and BRCA2 genes are a major cause of the hereditary form of the disease. Women inheriting these mutations have a 40 to 85 percent lifetime risk of developing breast cancer, as well as an increased risk of ovarian cancer.

To date, most of the studies on BRCA1 and BRCA2 mutations have focused on families known to be at high risk for breast cancer and on women who develop breast cancer at a relatively young age. The new study, published today in the journal Cancer Research, looked at the prevalence and predictors of BRCA1 and BRCA2 mutations in under-studied groups of women, such as African Americans and older women.

"Studies of any notable size have focused almost exclusively on white women and young women. This research clearly was needed to improve our means of assessing the likelihood of carrying BRCA1 and BRCA2 mutations in a wider spectrum of women," said one of the study's lead investigators, Elaine Ostrander, Ph.D., chief of the Cancer Genetics Branch in the National Human Genome Research Institute's Division of Intramural Research. Dr. Ostrander was previously head of the genetics program at the Fred Hutchinson Cancer Research Center, which is the institution that led the study.

The researchers examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 similar women without breast cancer, all of whom were participants in the National Institute of Child Health and Human Development's (NICHD's) Women's Contraceptive And Reproductive Experiences (CARE) study. The women involved in the study were white and African American women, ages 35 to 64, who lived in the Atlanta, Detroit, Los Angeles, Philadelphia and Seattle metropolitan areas.

"The advantages of this study include its large sample size, inclusion of under-studied groups of women and the fact that the results are population based," said one of the study's co-authors, Robert Spirtas, Dr.P.H, former chief of NICHD's Contraception and Reproductive Health Branch and now retired.

Researchers found that 2.4 percent of the breast cancer patients had BRCA1 mutations and 2.3 percent had BRCA2 mutations. BRCA1 mutations were more common among white breast cancer patients (2.9 percent) than among African American patients (1.4 percent). Breast cancer patients of Jewish ancestry were also significantly more likely to have BRCA1 mutations than non-Jewish patients – 10.2 percent compared to 2.0 percent. For BRCA2, African American patients were slightly more likely to have mutations, 2.6 percent, than were white patients, 2.1 percent.

Based on their findings, the researchers went on to calculate the prevalence of BRCA1 and BRCA2 mutations in the general U.S. population. Among white and African American women ages 35 to 64, the prevalence of BRCA1 mutations is 0.06 percent and the prevalence of BRCA2 mutations is 0.4 percent, the researchers estimated.

"These findings from our large, population-based study are compatible with earlier estimates made by extrapolating from smaller studies. However, we found a slightly lower frequency of BRCA1 mutations and a higher frequency of BRCA2 mutations," said the study's other lead investigator, Kathleen Malone, Ph.D., Member of the Public Health Sciences Division at the Fred Hutchinson Cancer Center. "We think the difference lies in the fact that earlier studies were confined mainly to whites, and that African American women carry BRCA2 mutations more often than white women."

The researchers also identified key predictors of whether a woman with breast cancer is likely to carry a BRCA1 or BRCA2 mutation. Such information is important because it can help to improve means of assessing which women may benefit the most from genetic testing, increased breast cancer screening and other measures aimed at early detection, treatment or prevention. The most significant predictors for BRCA1 mutations were: Jewish ancestry, a family history of ovarian cancer and a family history of breast cancer occurring before age 45.

For BRCA2 mutations, researchers uncovered fewer predictors, and they had more modest effects. Among the breast cancer patients studied, the only significant predictors of a BRCA2 mutation were early age of onset (before age 45) in the patient herself or early onset of breast cancer in mother, sisters, grandmothers or aunts.

"These findings underscore why women need to learn as much as they can about their family health history and then share that information with their health-care professionals. However, it must be emphasized that the presence or absence of a predictive factor does not automatically equate with a high or low likelihood of carrying a breast cancer gene mutation," said NIH Director Elias A. Zerhouni, M.D. "The majority of women with breast cancer – even those with a family history of the disease – do not carry mutations in these genes. These predictors need to be considered in the context of each woman's complete family health history."

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In addition to the Fred Hutchinson Cancer Center, NHGRI and NICHD, the team included researchers from the National Cancer Institute; Bay State Medical Center, Springfield, Mass.; the University of Pennsylvania, Philadelphia; University of Southern California, Los Angeles; and Wayne State University, Detroit.

Heart drug may block breast cancer gene

WASHINGTON, 03 june 2009– A gene that is highly active in up to 20 percent of breast cancer cases might be blocked by a generically available blood pressure drug, U.S. researchers reported on Tuesday.

The gene, called AGTR1, caused normal breast cells to behave like cancer cells but the blood pressure drug losartan stopped them, the team at the University of Michigan found.

They transplanted human tumors that expressed AGTR1 -- meaning the gene was active -- into mice. Eight weeks after they gave the mice losartan the tumors shrank by 30 percent, they reported in the Proceedings of the National Academy of Sciences.

"What's also exciting is this gene is blocked by a drug that's already available on the market," Dr. Arul Chinnaiyan, who led the study, said in a statement.

Chinnaiyan and colleagues looked at nearly 3,200 microarrays -- gene chips -- taken from cancer patients and available in a database called Oncomine, which was set up to allow just such comparisons.

The gene they found the most often was ERBB2 -- already known to be behind 25 percent to 30 percent of breast tumors. This gene mutation is targeted by Genentech's drug Herceptin, known generically as trastuzumab.

Number two in the scan was AGTR1, also known as angiotensin II receptor type I. They found it was busy in 10 percent to 20 percent of the breast tumors -- none of them ERBB2-positive tumors.

"AGTR1 is very analogous to HER2 or ERBB2. HER2 is a bona fide treatment target for patients with that type of breast cancer," said Chinnaiyan, whose work is funded by the Howard Hughes Medical Institute.

"Losartan may be a viable therapy for women with AGTR1 over-expressing breast tumors. This study lays the groundwork for a clinical trial to test losartan to treat breast cancers positive for AGTR1," Chinnaiyan says.

Losartan, made generically by India's Aurobindo Pharma Ltd, is the generic equivalent of Merck & Co Inc's Cozaar.

New Roche drug helps shrink breast cancer tumors

ZURICH, 29 may 2009 – A new drug from Roche Holding AG helped shrink the tumors of 25 percent of women with HER2-positive breast cancer, according to data from a mid-stage clinical trial, the Swiss company said on Thursday.

The treatment, trastuzumab-DM1, is a combination of Roche's Herceptin and a chemotherapy agent.

About 35 percent of patients 112 in the trial either saw their tumors shrink, or their disease stabilized for at least six months, Roche said.

Standard Chemo Found Superior to Capecitabine

Relapse, death twice as likely among older women with breast cancer in capecitabine group

18 may 2009-- Standard adjuvant chemotherapy was superior to capecitabine for treating older women with early breast cancer, though with substantial toxicity, according to research published in the May 14 issue of the New England Journal of Medicine.

Hyman B. Muss, M.D., of the University of Vermont in Burlington, and colleagues analyzed data from 633 women, ages 65 years and older, with early-stage cancer. Patients were randomized to receive capecitabine or standard chemotherapy, which consisted of cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin.

After median follow-up of 2.4 years, capecitabine was associated with a higher risk of disease recurrence or death, which was the primary measure of efficacy (hazard ratio, 2.09). Patients in this group were twice as likely to have a relapse and nearly twice as likely to die. However, moderate to severe toxic effects were twice as common in the standard chemotherapy group (64 versus 33 percent).

"For the treatment of older patients, the choice of chemotherapeutic agents, dose, schedule, and dose modification should be based on the treatment plans in published reports. Our data are part of a developing body of evidence that the choice of adjuvant chemotherapy really matters in older women with breast cancer and that standard chemotherapy is superior to the oral agent capecitabine," the authors conclude.

The study was supported in part by Roche Biomedical Laboratories. Several co-authors disclosed financial relationships with Hoffmann-La Roche.

Abstract
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Study shows chemotherapy improves survival among older breast cancer patients

14 may 2009--The average age of a woman diagnosed with breast cancer is 63, so it is critical to have effective proven, therapies for an older patient population. But older women with breast cancer are underrepresented in clinic trials, so there is little data on the effects of chemotherapy used in addition to other therapies such as surgery.

A new study, published in the May 14 issue of The New England Journal of Medicine, shows that chemotherapy in addition to the surgery or surgery and radiation improves survival among older women.

The study was conducted with 600 women through the Cancer and Leukemia Group B of the National Cancer Institute's Clinical Trials Cooperative Group Program.

"This study is important because it is among the first several trials specifically targeted to older women with early-stage breast cancer and shows that chemotherapy can make a difference," said Hyman Muss, M.D. professor of medicine at the University of North Carolina at Chapel Hill and a member of UNC Lineberger Comprehensive Cancer Center, and corresponding author on the study.

The study compared a combination of chemotherapy drugs – the standard treatment – to a single drug in patients with early-stage breast cancer aged 65 and older. The combination therapy provided significantly better outcomes than a single drug treatment.

Similar studies involving women younger than 70 years of age have also shown that combination therapies provide better outcomes.

For this trial, the standard chemotherapy consisted of either cyclophosphamide, methotrexate, and fluouracil (CMF) or doxorubicin plus cyclophosphamide. The single drug was the oral drug, capecitabine.

Because patients often prefer oral to intravenous chemotherapy, a new effective oral agent for multi-drug treatment would be useful in treating older women with breast cancer. But the study showed that patients who were randomly assigned to capecitabine were twice as likely to have a relapse, and at three-years after completing therapy, the rate of relapse-free survival was 68 percent in the capecitabine group versus 85 percent in the standard-chemotherapy group.

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The multi-institution trial included faculty from UNC Lineberger and Duke University, as well as clinical trials cooperative groups and institutions across the U.S. and Canada.

Lifetime exercise may cut breast cancer death risk

By Joene Hendry

NEW YORK, 17 april 2009– Women who participate in recreational exercise and sports over their lifetime may be lowering their risk of death from breast cancer and breast cancer recurrence.

Among 1,231 women with breast cancer who were followed for a minimum of 8.3 years, those who obtained about 4 hours or more of weekly moderate-intensity recreational activity over their lifetime had a 44 percent lower risk of death from breast cancer, report Dr. Christine Friedenreich and colleagues.

Risk for recurrence, progression, or new primary breast cancer was likewise reduced by 34 percent among women reporting similar levels of recreational physical activity, note Friendenreich, of Alberta Health Services-Alberta Cancer Board in Calgary, Canada, and colleagues.

These findings suggest "being physically active before a breast cancer diagnosis can improve survival after breast cancer," Friendenreich told Reuters Health.

However, occupational activity and physical household work such as gardening, housework, and do-it-yourself home repair did not confer benefits similar to those from lifetime exercise and sports activities, the investigators report in the International Journal of Cancer.

Friendenreich's team compared the lifetime physical activity reports of 1,231 women, who were 56 years old on average when diagnosed with breast cancer, with their outcomes. Over a minimum of 8.3 years of follow up, 341 women died (223 from breast cancer) and 327 had a recurrence, progressions, or new primary breast cancer diagnoses.

Compared with the least active women (less than 1.4 hours per week of recreational activity), those who engaged in more than 3.9 hours per week of moderate intensity recreational activity had 34 percent decreased risk for the combined outcomes, and 44 percent reduced risk for death from breast cancer.

These effects remained apparent after allowing for other factors potentially associated with survival such as body mass, tumor stage, and age.

Vigorous-intensity recreational activity lowered the risk of breast cancer mortality, but did not appear to reduce the risk of other outcomes.

Friendenreich notes her team continues examinations of "exactly what type and dose of activity is related to improved survival after cancer." Ultimately they hope this research leads to development of clear exercise guidelines for cancer patients.

Studies Support Menopausal Breast Cancer Risk Screening

Breast density improves estimations of risk; chemoprevention may benefit those at greater risk

18 mar 2009 -- Evidence supports screening postmenopausal women for risk of breast cancer and the consideration of chemoprevention for women at high risk, as well as the use of lifestyle changes for cancer prevention, according to research published in the March 18 issue of the Journal of the National Cancer Institute.

Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute in San Francisco, and colleagues reviewed prospective studies on methods of estimating women's risk of breast cancer, as well as interventions to reduce the risk.

The investigators found that risk models that rely on demographic factors and medical history had modest discriminatory accuracy for estimating risk. Breast density had a strong association with breast cancer, and incorporating density into models added to their discriminatory accuracy. In general, studies associated exercise, weight loss, a low-fat diet and lowered alcohol consumption with a smaller risk of breast cancer, the researchers report. Tamoxifen and raloxifene were also found to lower the risk of invasive breast cancer, they note.

"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. Several lifestyle changes can be recommended to postmenopausal women, regardless of their estimated risk category," the authors write.

Several study co-authors disclosed financial relationships with Eli Lilly, AstraZeneca, Pfizer and Novartis, and several have a patent on a device used in breast densitometry.

Abstract
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Reduced breast cancer risk: Physical activity after menopause pays off

16 jan 2009--Several studies had previously suggested that regular physical exercise reduces the breast cancer risk of women. However, it had been unknowned just how much exercise women should take in which period in life in order to benefit from this protective effect. Moreover, little was known about which particular type of breast cancer is influenced by physical activity.

Answers to these questions are now provided by the results of the MARIE study, in which 3,464 breast cancer patients and 6,657 healthy women between the ages of 50 and 74 years were questioned in order to explore the connections between life style and breast cancer risk. Participants of the study, which was headed by Professor Dr. Jenny Chang-Claude and conducted at the German Cancer Research Center and the University Hospitals of Hamburg-Eppendorf, were questioned about their physical activity during two periods in life: from 30 to 49 years of age and after 50.

A comparison between control subjects and breast cancer patients showed that women in the control group had been physically more active than patients. The scientists calculated the relative breast cancer risks taking account of the effect of other risk factors. Results show that the risk of developing breast cancer after menopause was lower by about one third in the physically most active MARIE participants compared to women who had generally taken little physical exercise.

For this reduced risk it is not necessary to work out hard at the gym. The women in the physically most active group, for example, walked for two hours every day and cycled for one hour, while the most inactive study participants walked for only about 30 minutes every day. The epidemiologists also discovered that physical activity in the postmenopausal period is particularly beneficial for reducing breast cancer risk.

A closer look at the types of breast cancer revealed that physically active women are less frequently affected, in particular, by tumors that form receptors for the two female sexual hormones, estrogen and progesterone. These malignant 'hormone receptor positive tumors' accounted for 62.5 percent of breast cancers among MARIE participants. Other tumor markers, such as HER2 receptor formation or differentiation stage of cancer cells, were found to be unrelated to physical activity.

The effect of physical activity was independent of weight gain, total energy intake or body mass index. Therefore, researchers assume that physical exercise reduces the risk of cancer through hormonal mechanisms instead merely by a reduction of body fat or other changes in physical constitution, as it has often been assumed.

"It doesn't always have to be sports," says Associate Professor Dr. Karen Steindorf of DKFZ, who has headed this analysis. "In our calculations we have also taken account of activities such as gardening, cycling or walking to the shops. Our advice to all women is therefore to stay or become physically active also in the second half of your life. You will not only reduce your risk of breast cancer, but it has been proven that your bones, heart and brain also benefit from it."

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Martina E. Schmidt, Karen Steindorf, Elke Mutschelknauss, Tracy Slanger, Silke Kropp, Nadia Obi, Dieter Flesch-Janys and Jenny Chang-Claude: Physical Activity and Postmenopausal Breast Cancer: Effect Modification by Breast Cancer Subtypes and Effective Periods in Life. Cancer Epidemiology Biomarkers and Prevention 2008, DOI: 10.1158/1055-9965.EPI-08-0479

High insulin levels raise risk of breast cancer in postmenopausal women

Elevated insulin may play a key role in the link between obesity and breast cancer

12 jan 2009 — Higher-than-normal levels of insulin place postmenopausal women at increased risk of breast cancer, researchers at Albert Einstein College of Medicine of Yeshiva University report. Their findings, published in the January 7 issue of the Journal of the National Cancer Institute, suggest that interventions that target insulin and its signaling pathways may decrease breast cancer risk in these women.

Breast cancer is the most common cancer among women in the United States. Last year, approximately 182,000 women were diagnosed with breast cancer and more than 40,000 died from the disease. The majority of breast cancers arise in women past the age of menopause.

Obesity is a well-established risk factor for postmenopausal breast cancer, but just how obesity and breast cancer are connected is unclear. Many researchers have assumed that the link is estrogen—a hormone that is known to increase breast-cancer risk and is found at higher-than-average levels in obese women. But obese women also have other hormonal imbalances that may play a role in triggering breast cancer. One such imbalance is elevated levels of insulin, which stimulates the growth of breast cells in tissue culture. The Einstein study is the first to prospectively identify insulin's role in breast cancer while controlling for estrogen levels.

The multi-year Women's Health Initiative (WHI)—the largest study of postmenopausal women ever funded by the National Institutes of Health—followed health outcomes in more than 93,000 postmenopausal women. At enrollment, each participant donated blood samples that were stored for later analysis.

In 2004, the Einstein researchers selected a subset of more than 1,600 of these participants: 835 who had developed breast cancer during the study, and a random sample of 816 women representative of the WHI as a whole. Using the blood samples and other measurements taken when the women enrolled, the researchers assessed their fasting insulin level, naturally occurring levels of estradiol (a form of estrogen), and body mass index, or BMI (a measure of obesity). After dividing the women into four groups based on their fasting insulin levels and controlling for estrogen levels, the researchers found that women with the highest insulin levels were nearly 50 percent more likely to have developed breast cancer compared with women who had the lowest insulin levels.

Most of this effect was observed in the large subset of women from the WHI study who did not use hormone-replacement therapy. HRT has a strong effect on insulin and other hormonal factors, so eliminating this variable gives a clearer picture of insulin's effect on breast cancer. "Among these women, the influence of insulin on breast cancer risk was quite high," says lead author Marc Gunter, Ph.D., assistant professor of epidemiology & population health at Einstein. "Women with the highest insulin levels in their blood were more than two times more likely to develop breast cancer than women with the lowest insulin levels." Moreover, "when we controlled for insulin, the association between obesity and breast cancer became much weaker," adds Dr. Gunter. "This means that a large component of that obesity-cancer relationship may be mediated by insulin levels."

The findings have important implications for prevention, and possibly treatment, of postmenopausal breast cancer, according to Howard Strickler, M.D., M.P.H, who was senior author of the paper and a professor of epidemiology & population health at Einstein. "Research now needs to focus on ways to reduce insulin's effects on cell growth and replication in the breast while preserving its positive metabolic effects.

There are several possibilities and working with our laboratory collaborators we hope to make fast progress," said Dr. Strickler.

"It is also possible that screening non-diabetic postmenopausal women for high insulin levels could prove useful in identifying individuals at high risk for breast cancer," says Dr. Strickler.

The current study is part of a broader research program at Einstein. Researchers are focusing on how the effects of insulin and insulin-like growth factors on cell replication and survival influence a variety of conditions. "Every cell in the body carries insulin receptors and most carry IGF-1 receptors, so it makes sense that this biologic pathway could play a major role in health and disease across a broad range of conditions and we have to do much more to understand these relationships,"notes Dr. Strickler. So far, studies by Dr. Strickler and his colleagues have shown that insulin and/or IGFs also play a role in endometrial and colorectal cancer, as well as the progression of certain viral diseases, including HIV, hepatitis C virus in the liver and human papillomavirus (the cause of cervical cancer).

New study firmly ties hormone use to breast cancer

By MARILYNN MARCHIONE

SAN ANTONIO, 13 dec 2008– Taking menopause hormones for five years doubles the risk for breast cancer, according to a new analysis of a big federal study that reveals the most dramatic evidence yet of the dangers of these still-popular pills.

Even women who took estrogen and progestin pills for as little as a couple of years had a greater chance of getting cancer. And when they stopped taking them, their odds quickly improved, returning to a normal risk level roughly two years after quitting.

Collectively, these new findings are likely to end any doubt that the risks outweigh the benefits for most women.

It is clear that breast cancer rates plunged in recent years mainly because millions of women quit hormone therapy and fewer newly menopausal women started on it, said the study's leader, Dr. Rowan Chlebowski of Harbor-UCLA Medical Center in Los Angeles.

"It's an excellent message for women: You can still diminish risk (by quitting), even if you've been on hormones for a long time," said Dr. Claudine Isaacs of Georgetown University's Lombardi Comprehensive Cancer Center. "It's not like smoking where you have to wait 10 or 15 years for the risk to come down."

Study results were given Saturday at the San Antonio Breast Cancer Symposium.

They are from the Women's Health Initiative, which tested estrogen and progestin pills that doctors long believed would prevent heart disease, bone loss and many other problems in women after menopause. The main part of the study was stopped in 2002 when researchers saw surprisingly higher risks of heart problems and breast cancer in hormone users.

Since then, experts have debated whether these risks apply to women who start on hormones when they enter menopause, usually in their 50s, and take them for shorter periods of time. Most of the women in the federal study were in their 60s and well past menopause.

So the advice has been to use hormones only if symptoms like hot flashes are severe, and at the lowest dose and shortest time possible. The new study sharpens that message, Chlebowski said.

"It does change the balance" on whether to start on treatment at all, he said.

Even so, most women will not get breast cancer by taking the pills short-term. The increased cancer risk from a couple of years of hormone use translates to a few extra cases of breast cancer a year for every 1,000 women on hormones. This risk accumulates with each year of use, though.

The Women's Health Initiative study had two parts. In one, 16,608 women closely matched for age, weight and other health factors were randomly assigned to take either Wyeth Pharmaceuticals' Prempro — estrogen and progestin — or dummy pills.

This part was halted when researchers saw a 26 percent higher risk of breast cancer in those on Prempro.

But that was an average over the 5 1/2 years women were on the pills. For the new study, researchers tracked 15,387 of these women through July 2005, and plotted breast cancer cases as they occurred over time.

They saw a clear trend: Risk rose with the start of use, peaked when the study ended and fell as nearly all hormone users stopped taking their pills. At the peak, the breast cancer risk for pill takers was twice that of the others.

Think of it as President Bush's public approval rating, said another study leader, Dr. Peter Ravdin of the University of Texas M.D. Anderson Cancer Center in Houston.

"Bush's popularity may be 50 percent on average, but it might have been descending the whole time he was president," Ravdin said.

In the second part of the federal study, researchers observed just 16,121 women who had already been on hormones for an average of seven years and another group of 25,328 women who had never used them. No results on breast cancer risk in these women have been given until now.

Plotting cases over time, researchers saw in retrospect that hormone users had started out with twice the risk of breast cancer as the others, and it fell as use declined. Among those taking hormones at the start of the study, use dropped to 41 percent in 2003, the year after the main results made news.

In the general population, use of hormone products has dropped 70 percent since the study, said another of its leaders, Dr. JoAnn Manson, preventive medicine chief at Harvard's Brigham and Women's Hospital in Boston.

That corresponds with big drops in breast cancer cases, but some scientists have said this could be due to a fall-off in mammograms, which would mean fewer cancers were being detected, not necessarily that fewer were occurring.

The new study puts that theory to rest. Mammography rates were virtually the same among those taking hormones and those not.

"It is clear that changing mammography patterns cannot explain the dramatic reductions in breast cancer risk," Manson said.

"The data are getting stronger," said Dr. C. Kent Osborne, a breast cancer specialist at Baylor College of Medicine in Houston.

Women who do need the pills should not panic, though the doubling of risk — a 100 percent increase — for long-term users is quite worrisome, cancer specialists say. Although the new study does not calculate risks in terms of actual cases, previous research showed that the average increased risk of 26 percent meant a difference of a few extra cases a year for every 1,000 women on hormone pills, compared with nonusers.

"Hormone therapy remains a good health care choice to relieve moderate to severe menopausal symptoms," says a statement from Wyeth, which made the pills used in the study.

"Most women should be able to discontinue hormones in three to four years," or at least reduce their dose, Manson said.

A future analysis will look at other women in the study who took only estrogen, generally women who have had hysterectomies.

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On the Net:

Cancer conference: http://www.sabcs.org

Hormone study: http://www.nhlbi.nih.gov/whi/estro_pro.htm

Patient management: Quality of life and beyond

SAN ANTONIO, 13 dec 2008 - Breast cancer is a multifaceted disease requiring creative solutions for diagnosis, quality of life management and adjuvant therapies. Data presented at the CTRC-AACR San Antonio Breast Cancer Symposium explore these areas.

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Hormone Supplements Reduce Death from Breast Cancer
Abstract #65, Sarah Marshall, M.A.

Although hormone supplements have been implicated in increased rates of breast cancer, they appear to mitigate the mortality risk of breast cancers that do develop. Compared with women who did not use hormone therapy, women who took estrogen-progestin were 63 percent less likely to die from breast cancer while those who took estrogen alone were 30 percent less likely.

Full release available/Complete data to be presented at the meeting.

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Tamoxifen Tops Anastrazole for Quality of Life, but not Survival
Abstract #1136, Shozo Ohsumi, M.D., Ph.D.
Embargo: 5:30 p.m. CST, December 11, 2008

After one to four years of tamoxifen, switching to anastrozole improves disease-free survival by about 31 percent, but patients pay a price in quality of life measures. The difference in quality of life is significant enough that scientists say it should be considered, and may even be the deciding factor, when making a clinical decision about therapeutic strategy.

Full release available/Complete data to be presented at the meeting.

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Letrozole following breast cancer surgery may provide survival benefit
Abstract #13, Alan Coates, M.D.
Embargo: 9:45 a.m. CST, December 11, 2008

Letrozole may improve overall survival in patients with primary breast cancer. A four-arm comparison study of letrozole and tamoxifen shows letrozole not only reduces recurrence, but may provide a 13 percent reduction in risk of death. Additionally, the study finds that using a sequence of tamoxifen and letrozole is not superior to letrozole alone. The sequence of letrozole followed by tamoxifen was closely similar to letrozole alone implying that patients can safely switch to tamoxifen after initial letrozole if required.

Complete data to be presented at the meeting.

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Use of Written Forms Doubles Breast Cancer Detection Rate
Abstract #5012, William Goodson, M.D.

When clinicians used simple written forms to focus attention during clinical breast exams, the rate of breast mass detection from the previous year doubled without retraining clinicians, thus affirming the importance of clinician attentiveness. This finding, researchers say, can be applied to all aspects of medicine and undermines the need for intensive training, complicated techniques, and medical reimbursement codes to improve this simple, yet valuable procedure.

Complete data to be presented at the meeting.

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The mission of the CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for breast cancer patients. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR), and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor, and the AACR's scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances into the clinic. The 31st Annual Symposium is expected to draw more than 8,500 participants from more than 80 countries.

New test aims to predict breast cancer risk better

By MARILYNN MARCHIONE

SAN ANTONIO, 13 dec 2008 – A new test to predict an ordinary woman's odds of getting breast cancer works better than a method doctors have relied on for decades, researchers reported Friday. The test is the first to combine dozens of genes and personal factors like age and childbearing to gauge risk in women who don't have a strong family history of the disease. They account for three-fourths of all cases.

In a California study to check its validity, the test correctly classified 50 percent more women with breast cancer as high risk than the current method did, and properly scored others lower. Results were given at a cancer conference in Texas.

But don't rush out to get it, cancer specialists plead. Even though this test and several others claiming to predict risk are available, more research is needed to prove their worth, they say.

"The market is being flooded with all these tests making all these claims," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"There's no 'Consumer Reports' of genetic testing" to rate their accuracy and usefulness, he said.

Women and doctors have long wished for a simple test that could reveal risk beyond the two BRCA genes, which tend to cause cancer at early ages but account for only a few percent of all cases. In the last year, four companies started selling broader multi-gene tests, but their value is widely disputed.

Women thought to be at high risk can get more frequent mammograms or MRI scans to check for breast cancer, or consider hormone-blocking drugs like tamoxifen. But even some advocates for better prevention approaches don't think gene tests are a good idea until more is known about the best treatment options.

"Are we going to give everyone chemotherapy or chop off everyone's breasts?" asked Barbara Brenner, head of the advocacy group Breast Cancer Action.

"It's terrifying people" to allow these tests to be sold without more information, she said.

The company that makes the new OncoVue test — Oklahoma City-based InterGenetics Inc. — aims to duck criticism by offering it only through doctors rather than directly to consumers, and validating it in population studies like the one reported Friday.

The $397 test looks for 22 single-letter variations in 19 genes that have been linked to breast cancer. The test is offered through 33 sites around the country, said Eldon Jupe, a geneticist and co-founder of the company.

Women fill out a medical questionnaire and use a mouthwash that releases cheek cells that are spit into a test tube and analyzed. A computer model weighs these factors to score cancer risk.

The test incorporates parts of the risk assessment tool that scientists and doctors use now — the Gail model, named after the National Cancer Institute biostatistician who developed it 20 years ago, Dr. Mitchell Gail. The factors include age, how many close relatives have had breast cancer, and when a woman started having periods or first gave birth.

It's a fairly crude model and studies have shown its many limitations, yet doctors and researchers rely on it so heavily that the Internet site for it is accessed 25,000 times a month, said Dr. Lynn Hartmann of the Mayo Clinic in Rochester, Minn.

"Better risk prediction is a huge need," she said.

The new study's leader, Dr. Kathie Dalessandri, a scientist at the University of California at San Francisco, wanted to see if OncoVue could outperform the Gail model in predicting risk in women in nearby Marin County, where breast cancer rates have been very high.

"It's been a puzzle for some time as to why," and BRCA genes do not explain it, Dalessandri said.

She did a previous study of 169 Marin County women diagnosed with breast cancer in the late 1990s and 177 women of similar age, weight and other factors identified through random phone calls. The Gail model was of little help sorting out why some had cancer and others did not.

For the new study, she used OncoVue on stored samples from that trial. OncoVue was two and a half times better at separating high and low risk women than the Gail model had been.

OncoVue put at high risk 19 more women who had breast cancer than Gail had — a 51 percent improvement, she said.

"It's an encouraging validation study," but needs more research in other population groups, said Dr. Kelly Marcom, who runs Duke University's Hereditary Cancer Clinic.

"The fact that they've been responsible in not doing direct-to-consumer marketing has been encouraging," he said of the test's makers. "I give them a great deal of credit for that."

The Food and Drug Administration has not approved gene tests and is considering guidelines for doing so. In the meantime, it has allowed many to be sold under existing rules that govern lab testing.

Some insurers cover some tests under certain circumstances.

The San Antonio Breast Cancer Symposium is sponsored by the American Association for Cancer Research and two universities.

Other tests on the market:

• Myriad Genetics Inc., based in Salt Lake City, sells the only tests for BRCA genes. Women with a faulty version have a three to seven times greater risk of developing breast cancer. Cost: $3,000.

• Iceland-based deCode Genetics Inc. offers through doctors a multi-gene test specifically for breast cancer, besides the whole-genome test it markets directly to the public. Cost $1,625 .

• Navigenics Inc. of Redwood Shores, Calif., sells a whole genome test that includes about 1 million gene variations including six for breast cancer. Sold directly to consumers. Cost: $2,500.

• 23andMe Inc., of Mountain View, Calif., also sells a whole-genome scan to the public. Only two of the nearly 600,000 gene variants in its test are specifically for breast cancer. Cost: $399

Study: Bone drug helps chemo fight breast cancer

By MARILYNN MARCHIONE

SAN ANTONIO, 12 dec 2008 – New research adds fresh hope that a drug that strengthens bones might also fight breast cancer. Women who were given the drug, Zometa, as part of their initial treatment had greater tumor shrinkage and were less likely to need radical surgery, according to a preliminary study reported Thursday at a cancer conference in Texas.

In June, doctors were stunned when a big study found that Zometa — given to prevent bone loss caused by certain cancer treatments — also greatly cut the risk that cancer would recur in women who developed the disease before menopause.

Cancer specialists are eagerly awaiting the final results of a second, ongoing study testing Zometa in 3,360 women who had breast cancer after menopause — a much more common situation.

Its leaders gave a mini-report Thursday on 205 participants who had chemotherapy to try to shrink their tumors before surgery.

Those given infusions of Zometa along with chemo had a third more tumor shrinkage and as a result, were less likely to need their whole breast removed versus just the lump, said study leader Dr. Robert Coleman of the University of Sheffield in England.

Eleven percent of Zometa takers had a complete response to treatment — no evidence of cancer in their breasts or lymph nodes — versus 6 percent of women given chemo alone.

Partial studies like this are not enough to change practice, but these results are surprising and deserve further testing, said Dr. Eric Winer of the Dana-Farber Cancer Center in Boston. Such significant benefits from the bone drug before surgery "is not something I would have expected," he said.

Winer had no role in the work or financial ties to any breast cancer drugmakers. He also is a spokesman for the American Society of Clinical Oncology, the largest group of doctors who treat cancer.

The study was sponsored by Zometa's maker, Swiss-based Novartis AG, and the study leader consults for the company. With doctor fees, a Zometa infusion can run more than $1,200. In the study it was given every three weeks for four to six months.

Known side effects of Zometa and other bone-building bisphosphonate drugs like Fosamax include bone, joint or muscle pain and in rare cases, jawbone decay. They are mainly used to treat osteoporosis.

Also at the conference, several reports strengthened evidence that newer hormone-blockers called aromatase inhibitors, or AIs, do a better job of preventing cancer recurrences and may give a slight survival advantage over the long-used drug tamoxifen.

These drugs work against estrogen, which helps most breast tumors grow, and are given for about five years after surgery for early stage breast cancer to prevent its return.

Tamoxifen has been used for decades and is sold in generic form for about $70 a month. The newer drugs cost around $300 and come in three brands: AstraZeneca PLC's Arimidex (anastrozole), Pfizer Inc.'s Aromasin (exemestane) and Novartis' Femara (letrozole). They only work in women after menopause.

Doctors already know that women who take these newer drugs either as initial treatment or after a few years of tamoxifen have better chances of staying cancer-free. But which of these approaches is best is not known.

Results of a study led by Novartis consultant Dr. Henning Mouridsen of Copenhagen University Hospital in Denmark mostly were a draw. There were trends toward improved survival for women starting on Femara, but the differences were so small they could have occurred by chance alone.

Specialists took issue with a separate analysis of that study, which hinted at a bigger benefit from starting on Femara. And pooled results of prior studies involving 20,000 women suggest that any such advantage is very small.

"At this point in time, there is a slight increase in survival in patients treated with AIs but it is not statistically significant," said that study's leader, Dr. James Ingle of the Mayo Clinic in Rochester, Minn.

"The only really fair interpretation is that all of these are the same," and that women should include one at some point in their treatment as guidelines now recommend, Winer said.

About 90,000 women in the United States and many more worldwide each year face this decision, and key issues are cost and side effects.

Both drugs can cause hot flashes. Tamoxifen raises the risk of endometrial cancer and blood clots. The aromatase inhibitors can cause more bone loss, vaginal dryness, problems having sex, joint pain and muscle aches.

"Many of us think that overall, they're drugs that are a little harder to take," Winer said of the newer drugs.

"When you put it all together it's almost a balancing act," depending on each woman's health history and risks, said Dr. C. Kent Osborne, a breast cancer specialist at Baylor College of Medicine in Houston.

The San Antonio Breast Cancer symposium is sponsored by the American Association for Cancer Research, Baylor and the University of Texas Health Science Center at San Antonio.

Some Breast Cancers May Regress on Their Own

By Amanda Gardner
29 nov 2008- Some breast cancers may naturally disappear without treatment, a study of women undergoing mammography suggests.
The Norwegian study found that more cases of breast cancer were diagnosed after a regular screening program was put in place than before. That has led specialists to suspect that some of the diagnosed tumors would have spontaneously regressed had they not been detected and treated as the result of more rigorous mammography guidelines.
But since doctors can't yet determine which tumors might regress and which might go on to be dangerous, the finding isn't likely to change recommendations for mammography, experts said.
"The problem is, we don't know the natural history [of breast cancer]," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "I am sure there are some that do regress. The problem is, we can't pick up those that are going to regress. It's one of the unanswerable questions."
The study was published in the Nov. 24 issue of the Archives of Internal Medicine.
Cancer experts have long suspected that some cancers may grow and then, for reasons that are unclear, simply shrink again and disappear. The new breast cancer trial appears to support that notion.
The study took advantage of the fact that new biennial (once every two years) screening mammography programs were instituted throughout Europe in the 1990s. Such a program began in Norway in 1996.
Researchers from the Norwegian Institute of Public Health tracked the incidence of breast cancer among more than 119,000 women aged 50 to 64 who participated in three rounds of biennial mammography screening between 1996 and 2001.
They then compared that data to the rates of breast cancer for almost 110,000 women of similar age between 1992 and 1997, largely before the new guidelines came into effect. When Norway began offering mammograms in 1996, almost all these women went and got a one-time screen.
Although it might be expected that the two groups of women would have breast cancer at similar rates, they did not. In fact, the women in the later cohort -- who got mammograms once every 2 years -- had a 22 percent higher rate of tumors than the women in the earlier, less heavily screened group.
According to the authors, changes in hormone therapy use over the study period did not explain the difference. So why would more frequent screening mean more cancers?
What probably happened, the authors theorized, is that some of the tumors detected during more frequent screening would not otherwise have caused women trouble if they had remained undetected. These tumors might have either remained stable or, more likely, spontaneously regressed.
In fact, there have been 32 cases of spontaneous regression of breast cancer reported in one recent review of the medical literature. And not all actual cases of spontaneous regression end up being documented.
In addition, autopsy studies have revealed that many women die without ever knowing they had a breast cancer.
One expert was intrigued by the findings.
"The study is very provocative and it generates an interesting hypothesis: that it's possible some screen-detected breast cancers would not ever lead to death from breast cancer and are unnecessarily diagnosed and treated," said Dr. Jeanne Mandelblatt, associate director for population sciences at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C.
"But this study design can't prove or disprove that hypothesis," she added. "This study is inconclusive because these women were not randomized; there's no data about the tumor sizes or tumor characteristics in the two groups, and no data about the breast cancer death rate in the two groups."
Still, the finds should impact breast cancer research, experts say. "If the spontaneous remission hypothesis is credible, it should cause a major re-evaluation in the approach to breast cancer research and treatment," wrote Robert Kaplan, of the University of California, Los Angeles, and Dr. Franz Porzsolt of the Clinical Economics University of Ulm, Germany, in an editorial that accompanied the journal article. "Certainly, it is worthy of further evaluation."
Right now, however, doctors cannot tell a "bad" breast tumor from a potentially harmless one, so regular mammography screening is still valuable.
"For women, the take-home message remains that mammography done as recommended does decrease the chance of dying from breast cancer across the general population," Mandelblatt said. "Women need to know that there are risks and benefits to all medical interventions, including screening mammography, and the policy recommending mammography is based on the fact that the benefits outweigh some of these harms."