Study: Moderate red wine drinking may help cut women’s breast cancer risk

Posted on by
Reply

LOS ANGELES – Drinking red wine in moderation may reduce one of the risk factors for breast cancer, providing a natural weapon to combat a major cause of death among U.S. women, new research from Cedars-Sinai Medical Center shows.

The study, published online in the Journal of Women’s Health, challenges the widely-held belief that all types of alcohol consumption heighten the risk of developing breast cancer. Doctors long have determined that alcohol increases the body’s estrogen levels, fostering the growth of cancer cells.

But the Cedars-Sinai study found that chemicals in the skins and seeds of red grapes slightly lowered estrogen levels while elevating testosterone among premenopausal women who drank eight ounces of red wine nightly for about a month.

White wine lacked the same effect.

Researchers called their findings encouraging, saying women who occasionally drink alcohol might want to reassess their choices.

“If you were to have a glass of wine with dinner, you may want to consider a glass of red,” said Chrisandra Shufelt, MD, assistant director of the Women’s Heart Center at the Cedars-Sinai Heart Institute and one of the study’s co-authors. “Switching may shift your risk.”

Shufelt noted that breast cancer is the leading type of women’s cancer in the U.S., accounting for more than 230,000 new cases last year, or 30 percent of all female cancer diagnoses. An estimated 39,000 women died from the disease in 2011, according to the American Cancer Society.

In the Cedars-Sinai study, 36 women were randomized to drink either Cabernet Sauvignon or Chardonnay daily for almost a month, then switched to the other type of wine. Blood was collected twice each month to measure hormone levels.

Researchers sought to determine whether red wine mimics the effects of aromatase inhibitors, which play a key role in managing estrogen levels. Aromatase inhibitors are currently used to treat breast cancer.

Investigators said the change in hormone patterns suggested that red wine may stem the growth of cancer cells, as has been shown in test tube studies.

Co-author Glenn D. Braunstein, MD, said the results do not mean that white wine increases the risk of breast cancer but that grapes used in those varieties may lack the same protective elements found in reds.

“There are chemicals in red grape skin and red grape seeds that are not found in white grapes that may decrease breast cancer risk,” said Braunstein, vice president for Clinical Innovation and the James R. Klinenberg, MD, Chair in Medicine.

###

The study will be published in the April print edition of the Journal of Women’s Health, but Braunstein noted that large-scale studies still are needed to evaluate the safety and effectiveness of red wine to see if it specifically alters breast cancer risk. He cautioned that recent epidemiological data indicated that even moderate amounts of alcohol intake may generally increase the risk of breast cancer in women. Until larger studies are done, he said, he would not recommend that a non-drinker begin to drink red wine.

The research team also included C. Noel Bairey Merz, MD, director of the Women’s Heart Center, director of the Preventive and Rehabilitative Cardiac Center and the Women’s Guild Chair in Women’s Health, as well as researchers from the University of Southern California Keck School of Medicine and Hartford Hospital in Connecticut.

Source: Eurekalert

Risk for developing new cancer in other breast increased for survivors with BRCA mutation

Posted on by
Reply

SAN ANTONIO — Breast cancer survivors who carry the BRCA1 or BRCA2 genetic mutation are at high risk for developing contralateral breast cancer — a new primary tumor in the other breast — and certain women within this group of carriers are at an even greater risk based on age at diagnosis and first tumor status, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

“Our studies show that certain subgroups of women [with this mutation] who have already had cancers are also at risk for developing a second new cancer in their other breast, much more so than survivors who do not carry the mutation,” said Alexandra J. van den Broek, M.Sc., a doctoral candidate at the Netherlands Cancer Institute. “Our study is, as far as we know, the first study showing that within certain carriers of BRCA mutations, subgroups with an increased or decreased risk for contralateral breast cancer (CBC) can be made.”

Researchers surveyed 5,061 women diagnosed with unilateral, invasive breast cancer at 10 hospitals in the Netherlands. Two hundred eleven women (4.2 percent) were carriers of the BRCA1 or BRCA2 mutation. Overall, at a median of 8.4 years of follow-up, 8.6 percent of participants developed CBC.

Van den Broek and colleagues found that the overall 10-year risk for developing CBC in noncarriers was 6.0 percent, while risk for carriers was 17.9 percent.

For carriers diagnosed with their first breast cancer when aged younger than 40 years, the 10-year risk for CBC jumped to 26.0 percent. For carriers between the ages of 40 and 50 years at first diagnosis, the risk was 11.6 percent. In addition, mutation carriers with a triple-negative first tumor had a 10-year cumulative CBC risk of 18.9 percent compared with 11.2 percent among carriers with a non-triple-negative first tumor.

Although these numbers can be overwhelming to carriers who have already survived breast cancer, van den Broek said it is crucial to know who is most at risk and by how much.

“Guidelines for prophylactic measures and screening in the follow-up of patients with breast cancer carrying the BRCA1 or BRCA2 mutation are important to provide patients with the best information and counseling,” she said. “If these results are confirmed, [it will be] possible to personalize the guidelines for these specific subgroups.”

The next step will be to confirm the results in larger studies and to look at other factors that define subgroups of patients with an increased or decreased risk for CBC.

Source Eurekalert December 8 2011

Many women do not undergo breast reconstruction after mastectomy

Posted on by
Reply

SAN ANTONIO — Despite the benefits, only a small minority of women, regardless of age, are opting for immediate reconstructive breast surgery after undergoing mastectomy for treatment of breast cancer, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Research has shown that immediate breast reconstruction after mastectomy improves psychological well-being and quality of life and provides women with improved body image and self-esteem compared with delaying the procedure.

However, data from this study, presented by Dawn Hershman, M.D., associate professor of medicine and epidemiology at Columbia University Medical Center in New York, indicate that only about one third of women undergo the procedure.

Hershman and colleagues identified 106,988 women with breast cancer who underwent mastectomy between 2000 and 2010. They identified these women using insurance codes and then examined data on the frequency of reconstruction by a number of factors including age, race, number of procedures performed in the hospital and type of insurance.

Of the women examined, 22.6 percent underwent immediate reconstruction. Although overall rates of reconstruction have increased since 2000, the greatest increases were seen among women with commercial insurance — from 25.3 percent to 54.6 percent — and among women aged younger than 50 years — from 29 percent to 60 percent. Among women aged 50 years or younger who also had commercial insurance, 67.5 percent underwent immediate breast reconstruction. Overall, women with commercial insurance had more than a threefold higher likelihood of undergoing immediate reconstruction compared with women without health insurance.

“We were surprised to see that although the use of immediate postmastectomy reconstruction has increased, the rates still remain low, with 41.8 percent of women aged younger than 50 years and less than 20 percent of women aged older than 50 years receiving reconstruction during this time frame,” Hershman said.

Researchers found that patients were more likely to undergo immediate reconstruction if their surgeon did more mastectomies or they were in a hospital where more mastectomies were performed.

“This is something that could be modified by training and patient education,” Hershman said.

Other factors associated with a decreased likelihood for undergoing mastectomy were increasing age, black race, rural hospital location, nonteaching hospital or having other medical illnesses.

Women who underwent immediate breast reconstruction postmastectomy did have a longer hospital stay, but in-hospital complication rates were similar between women who had reconstruction and those who did not.

“Our study shows that there are factors that can be modified to increase the likelihood that women undergo postmastectomy reconstruction,” Hershman said. “Public policy should ensure that access to reconstructive surgery is available to all women regardless of insurance status.”

In the future, Hershman and colleagues plan to explore other factors that may be associated with immediate reconstruction to better target interventions to appropriate institutions.

Source Eurekalert December 8 2011

Low Risk Prostate Cancer: Panel endorses active monitoring

Posted on by
Reply

An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.

“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.

Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.

Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.

The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.

Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease,” stated Dr. Ganz.

The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.

The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.

With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.

The state-of-the-science conference was sponsored by the NIH Office of Medical Applications of Research, the National Cancer Institute, and the Centers for Disease Control and Prevention, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement.

In addition to the material presented at the conference by speakers and the comments of conference participants presented during discussion periods, the panel considered pertinent research from the published literature and the results of a systematic review of the literature. The systematic review was prepared through the Agency for Healthcare Research and Quality Evidence-based Practice Centers (EPC) program by The Tufts Medical Center Evidence-based Practice Center. The EPCs develop evidence reports and technology assessments based on rigorous, comprehensive syntheses and analyses of the scientific literature, emphasizing explicit and detailed documentation of methods, rationale, and assumptions. A link to the evidence report on the role of active surveillance in the management of men with localized prostate cancer is available at http://consensus.nih.gov/2011/prostate.htm.

The panel’s statement is an independent report and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 as a mechanism to judge controversial topics in medicine and public health in an unbiased, impartial manner.

Obese patients with HER2-positive breast cancer may have worse outcomes

Posted on by
Reply

SAN ANTONIO — Obese patients with early-stage HER2-positive breast cancer may have worse outcomes than patients who are normal weight or overweight, Mayo Clinic researchers found in a study presented today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. HER2-positive breast cancer gets its name from a protein called human epidermal growth factor receptor 2 that promotes cancer cell growth.

“Not only did obese women have poorer outcomes given several different therapies tested to treat HER2-positive breast cancer, but we know that obese patients in our study had larger tumors and were more likely to have had cancer detected in their lymph nodes, compared to patients who were not obese,” says the study’s lead author, Jennifer Crozier, M.D., a medical resident.

“While other studies have looked at the effect of body weight on treatment outcome for estrogen receptor-positive breast cancer, no one has examined this variable in the HER2-positive subtype, which accounts for about one-third of all breast cancers,” says Dr. Crozier.

Researchers used data from the North Central Cancer Treatment Group N9831 study for their analysis. This phase III randomized clinical trial tested three different options for treatment of early stage HER2-positive breast cancer: chemotherapy alone (Arm A); chemotherapy followed by Herceptin for a year (Arm B); and chemotherapy plus Herceptin, followed by Herceptin for a year (Arm C).

In a review of data from 3,017 patients, researchers found that, considering all three treatment arms together, obese patients — those with a body mass index (BMI) of 30 or more — had worse outcomes than patients with a BMI less than 30, although these trends were not statistically significant.

Researchers then calculated disease-free survival for each study arm for normal weight, overweight and obese patients, and found that patients fared best in Arm C. In this arm, the difference between BMI and outcome was not statistically significant, Dr. Crozier says. Herceptin was powerful enough to provide an equal benefit in patients with vastly varying body weights, she says.

“We are continually searching for approaches that will help our patients have the best outcome possible after their diagnosis of breast cancer, and this study suggests that excess body weight may make a difference,” says senior investigator Edith Perez, M.D., director of Mayo Clinic’s breast program in Florida.

###

The study was funded by the National Institutes of Health, Genentech, Bayer, and the Breast Cancer Research Foundation.

Source: Eurekalert December 8 2011

Judicious PSA, Testing, Can Help Reduce Unnecessary Prostate Biopsies

Posted on by
Reply

BOSTON – Prostate cancer screening that combines an adjusted blood test with other factors including the size of the gland, the patient’s overall weight and family history, can help up to one-quarter of men avoid biopsies and the risks associated with them, a Beth Israel Deaconess Medical Center-led research team says.

Writing in a study published online by the journal Cancer, the team led by Martin G. Sanda, MD, Director of the Prostate Center at Beth Israel Deaconess Medical Center and Professor of Urology at Harvard Medical School, suggests that instead of using “one-size-fits-all” levels of PSA to determine who should have a biopsy, considering other factors such as prostate size can substantially improve the ability of PSA testing to identify aggressive prostate cancers for which treatment is warranted, while avoiding detection of indolent cancers that are better undiagnosed because they do not require treatment.

Source: Eurekalert December 8 2011

A second study led by Sanda, and published online in the journal Urologic Oncology, suggests the presence or absence of genes commonly found in the urine of men, when combined with a PSA test, can also be used to determine whether a biopsy is necessary.

The new suggested approaches come as the United States Preventive Services Task Force expert panel concluded that current PSA-based prostate cancer screening saves few or no lives, but causes harm through treatment or further invasive testing such as biopsies. That’s because prostate cancers can vary in aggressiveness and more men die of other causes aside from that cancer – and because the PSA test alone cannot determine how dangerous any particular cancer may be.

“The US Preventative Services Task Force threw the baby out with the bathwater by their blanket recommendation against prostate cancer screening,” says Sanda, noting that PSA screening can instead be refined to more selectively identify only aggressive cancer for which treatment is indicated by adjusting PSA results for other considerations such as family history, obesity, and prostate size.

Results from the multi-center study that suggest that PSAD levels of less than 0.1 – in contrast to the unadjusted level of between 2.5 and 4 – can be a better benchmark of a potential cancer. The density, determined by a digital rectal exam, enables physicians to take into account other factors like benign prostatic hyperplasia, an enlargement of the gland that affects all men as they age.

Combining the PSAD with the digital exam, a look at the patient’s family history and a body mass index of 25 of less – the calculation used to define obesity – would avoid biopsy in approximately one-quarter of biopsy-eligible men, the researchers found.

“Urological practice, patient outcome and cost-effectiveness of health care would each benefit from new targeted strategies, such as nomograms (a predictive tool) that improve prediction of aggressive cancers, to enable selective identification of candidate for prostate biopsy that would improve the yield of clinically significant, histologically aggressive cancers warranting subsequent definitive treatment,” researchers wrote.

In a separate multicenter study published in Urologic Oncology, researchers said a test looking for two specific genetic biomarkers – TMPRSS2:ERG and PCA3 – taken after a digital rectal exam, could help limit biopsies to men who possess both genes and whose PSA readings range between 2 and 10, potentially sparing one-third of men from biopsies.

“Urine testing for prostate cancer is in its infancy,” says Sanda, noting next steps are underway as a result of study funded by a $3.1 million grant from the National Institutes of Health , that is evaluating new urine and blood test for prostate cancer in more 2,400 men over the next five years with a goal of improving upon the problems of over-diagnosis and over-treatment.

A focal point of the proposed work involves a community outreach effort led by BIDMC primary care physician J. Jacques Carter, MD, MPH, Medical Director of the Dana Farber Cancer Institute Prostate Cancer Screening and Education Program and an Assistant Professor of Medicine at Harvard Medical School. A key component of this study will be African-American men, who appear to develop prostate cancer more frequently, and who are at increased risk of dying from prostate cancer.

In addition to Sanda, co-authors of the Cancer study are: Stephen B. Williams of BIDMC, Brigham and Women’s Hospital and Harvard Medical School; Simpa Salami, MD, MPH of BIDMC; Meredith M. Regan, ScD of Harvard Medical School and the Dana Farber Cancer Institute; Ian M. Thompson MD and Donna P. Ankerst, PhD of the University of Texas Health Science Center at San Antonio; John T. Wei, MD of the University of Michigan; and Mark A. Rubin MD of Weill Cornell Medical College in New York.

The study was supported by the National Cancer Institute.

In addition to Sanda, Salami, Regan, Rubin and Wei, co-authors of the Urologic Oncology article are: Gerardina Bueti, BS of BIDMC; Folke Schmidt, MD, David S. Rickman PhD and Douglas Scherr, MD of Weill Cornell Medical College in New York; Bharathi Laxman, PhD, Javed Siddiqui, MS, Scott A. Tomlins, MD, PhD and Arul Chinnaiyan, MD, PhD of the University of Michigan.

The study was supported by the National Cancer Institute.

Researchers find genetic rearrangements driving 5 to 7 percent of breast cancers

Posted on by
Reply

ANN ARBOR, Mich. — Researchers at the University of Michigan Comprehensive Cancer Center have discovered two cancer-spurring gene rearrangements that may trigger 5 to 7 percent of all breast cancers.

These types of genetic recombinations have previously been linked to blood cancers and rare soft-tissue tumors, but are beginning to be discovered in common solid tumors, including a large subset of prostate cancers and some lung cancers.

Looking at the genetic sequencing of 89 breast cancer cell lines and tumors, researchers found two distinct types of genetic rearrangements that appear to be driving this subset of breast cancers. The recurrent patterns were seen in the MAST kinase and Notch family genes. The findings were published online in Nature Medicine ahead of print publication.

“What’s exciting is that these gene fusions and rearrangements can give us targets for potential therapies,” says Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. “This is a great example of why treating cancer is so challenging. There are so many different ways genes get recombined and so many molecular subtypes, that there’s not one solution that will work for all of them.”

“The research provides additional evidence that these types of genetic rearrangements seem to be a significant cause of solid tumors,” he adds.

The discoveries illuminate a promising path for future research, Chinnaiyan says. Gene sequencing offers opportunities to develop treatments for individuals whose tumors carry specific genetic combinations – a process commonly known as “personalized medicine.”

The study demonstrated that the genetic rearrangements had profound effects on breast cancer cells in the lab, both in tissue culture and in mouse models.

“We cloned each of these rearrangements and introduced them into normal breast cell lines, where they appeared to have cancer-causing effects,” Chinnaiyan says.

Previous U-M research showed that half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event for these prostate cancers, was initially discovered in 2005 by U-M researchers led by Chinnaiyan.

###

Additional authors: Dan R. Robinson, Shanker Kalyana-Sundaram, Yi-Mi Wu, Sunita Shankar, Xuhong Cao, Bushra Ateeq, Irfan A. Asangani, Matthew Iyer, Christopher A. Maher, Catherine S. Grasso, Robert J. Lonigro, Michael Quist, Javed Siddiqui, Rohit Mehra, Xiaojun Jing, Thomas J. Giordano, Michael S. Sabel, Celina G. Kleer, Nallasivam Palanisamy, Chandan Kumar-Sinha, all of U-M. Kalyana-Sundaram also of Bharathidasan University, Tiruchirappalli, India

Rachael Natrajan, Maryou B. Lambros, Jorge S. Reis-Filho, of the Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.

Disclosures: The researchers report no conflicts of interest. U-M has filed for patent protection for these developments.

Funding: The specific aims of this project were supported by the Department of Defense Breast Cancer Research Program. The project was also supported in part by an American Association for Cancer Research Stand Up to Cancer (SU2C) breast cancer award, the National Functional Genomics Center supported by the Department of Defense, and the National Institutes of Health. Chinnaiyan is supported by the National Cancer Institute Early Detection Research Network, the Doris Duke Charitable Foundation and the Burroughs Welcome Foundation; he is also an American Cancer Society research professor and Taubman Scholar.

Source: Eurekalert

Study: Gene impedes recovery from Alcoholism

Posted on by
Reply

People who are alcohol-dependent and who also carry a particular variant of a gene run an increased risk of premature death. This is a recent finding from the interdisciplinary research at the Department of Psychology and the Sahlgrenska Academy at the University of Gothenburg, Sweden.

Researchers in the longitudinal project Göteborg Alcohol Research Project (GARP) have been investigating the dopamine D2 receptor gene and found that a variant of this gene is overrepresented in people with severe alcohol dependency, and that it is linked to a number of different negative consequences that can be of vital significance to the person affected.

“Our research shows that alcohol-dependent individuals, who are also carriers of this gene variant, run 10 times the risk of dying prematurely, compared with the average population,” says Claudia Fahlke, a representative from the research team.

In a study published recently in the journal Alcohol and Alcoholism (issue 46), the research team shows that this gene variant also appears to be associated with a higher tendency among these individuals to suffer a relapse, even if they have undergone treatment for their alcohol dependency. This may provide one explanation as to the higher mortality rate in people suffering from alcohol dependency, who are carriers of this gene variant.

“This knowledge emphasises the importance of developing methods for early identifying individuals who are also carriers of this gene variant, since the consequences can be so serious,” says Jan Balldin at the Sahlgrenska Academy, University of Gothenburg.

Linking of mutations in 12 genes to ovarian cancer may lead to more effective prevention

Posted on by
Reply

October 25 2011
More patients with ovarian carcinoma carry cancer-predisposing mutations, and in more genes, than previously thought.

A rapid experimental method for screening genomes has located mutations in 12 genes for inherited cancers of the ovary, fallopian tubes and peritoneum (the thin tissue lining the lower abdomen).

More than one-fifth of ovarian cancers arise in women with a familial predisposition, but relying on family history would have missed one-third of the cases, said Dr. Elizabeth Swisher, senior author of a paper on these findings published online ahead of print in the Proceedings of the National Academy of Sciences.

Swisher is an associate professor of obstetrics and gynecology at the University of Washington in Seattle. She directs the Breast and Ovarian Cancer Prevention program at the UW and the Seattle Cancer Care Alliance, and is an affiliate researcher at the Fred Hutchinson Cancer Research Center.

The results of her most recent study have far reaching implications beyond the important identification of mutations linked to ovarian and related cancers.

The speedy, low-cost genome analysis method her team developed could soon be applicable to patient testing for a broad range of all known breast, ovarian, colon, pancreatic and melanoma gene mutations. A single test might be able to screen a patient for susceptibility to all these cancers.

Also, the great number of specimens that this method can analyze simultaneously could allow for large scale, population studies of cancer-causing mutations. Such studies would tell who is at risk for certain cancers and how to effectively target prevention.

The UW scientists named their sequencing method BROCA, after Paul Broca, a 19th century medical scientist who was among the first to describe inherited breast and ovarian cancer. BROCA, the researchers said, is highly sensitive and can find all classes of genetic mutations, including single substitutions, small insertions and deletions, and large rearrangements of genes.

“The BROCA test is not patented,” the researchers said, and added that designs for its use in genetic studies are freely available.

At present, most tests for genes already known to be associated with breast and ovarian cancer, BRAC1 and BRAC2, are done by a lone company. The cost is about $4,000 for a non-comprehensive test accompanied by an additional test to find gene rearrangements.

As more cancer-susceptibility genes are found, it is not economical to test a person for one gene mutation, and then go back and test for another, then another. Gene-by-gene testing will eventually give way to a single test that accurately identifies all classes of those gene mutations that permit tumors to grow unchecked.

At present, the price for the BROCA chemicals is about $200. The costs are shrinking for running the genome analysis, due to the increasing number of samples that can be put through the multiple “lanes” in the sequencer.

Swisher and her team concentrated on ovarian cancer gene-detection in trying this sequencing method because ovarian cancer is one of the most deadly to affect a woman’s reproductive system. It is difficult to diagnose in its early stages

Ovarian cancer and cancer of the peritoneum begin quietly. Eventually vague symptoms appear, but they mimic seemingly benign conditions, like bloating.

“Most women are not diagnosed until the cancer is has advanced to the point where the chances of a cure are small,” Swisher said. “Women with early stage ovarian cancer have a better survival than those diagnosed with late stages, but current methods of detection are not effective.”

The lack of effective early detection is why Swisher and her research team are looking for a more complete genetic picture of ovarian and related cancers. Learning the genetic mutations associated with these cancers could lead to tests to identify early on the women prone to these malignancies.

A quick, low cost, individual screening test for a variety of gene mutations linked to ovarian cancer would allow for effective preventive measures, the researchers said. For example, a woman whose genetic profile indicates high risk could consider an operation to remove her ovaries and fallopian types. This procedure has already been shown to decrease the overall death rate in women who have BRCA1 or BRAC2 mutations.

These particular mutations heighten the risk of ovarian as well as breast cancer. As this current study reveals, previously unknown mutations in other genes also occur in the population of women diagnosed with ovarian cancer.

New developments in cancer drugs that selectively wipe out cells containing certain genetic deficiencies is another major incentive for scientists to locate other mutations involved in ovarian cancer, Swisher noted. For example, the new drug class called poly-ADP-ribose polymerase (PARP) inhibitors is lethal to cells missing chemicals produced by normal BRAC1 and BRAC2 genes. The PARP drugs are showing efficacy in treating ovarian cancers in patients with mutations in these genes.

The UW scientists applied BROCA to analyze the DNA from a 360 women undergoing surgery between 2001 and 2010 at the University of Washington for cancer of the ovaries, peritoneum, or fallopian tubes, or who had cancer of the ovaries as well as the uterine lining. The women were enrolled at diagnosis. Neither age of onset of the cancer nor their family history were selection factors.

Among this group of women, the researchers found 85 mutations in 12 genes. Many were loss-of-function mutations. An example of loss of function is the inability of cells to produce chemicals to suppress tumors. As the scientists expected, women with a personal history of breast cancer had an extremely high likelihood of harboring an inherited mutation. Family history of breast, ovarian, uterine, and pancreatic cancer – but not colon cancer – were each associated with inherited mutations.

“An observation that has major implications for clinical practice was that nearly one-third of the women with inherited mutations had no prior personal history of breast cancer and no family history of ovarian or breast cancer,” Swisher noted. This high proportion of unrecognized risk, she explained, is probably due to the combined effects of small family size, female cancer genes inherited from unaffected fathers, and the simple odds of a mutated gene being inherited or not inherited.

The researcher also found that the age when these types of cancer appear was not generally associated with the likelihood of having an inherited mutation, or with the gene in which a mutation was found.

There were no significant differences in survival rates between women who had one or more of the mutations identified in this study, and women who did not have these particular mutations.

What we found overall, the researchers noted, was that more than one in five cases of ovarian carcinoma were associate with a mutation in tumor suppressor genes. In their normal form, these genes act in a way that keeps tumors from growing.

The findings of this study, the researcher concluded, point to the need to develop comprehensive testing for inherited carcinoma for all women with ovarian, peritoneal or fallopian tube cancer, regardless of their age or family history. The researchers are moving clinical science forward to a time when expensive single gene testing for thousands of dollars will be replaced by testing many genes simultaneously at low cost.

###

In addition to Swisher, the scientists on this project were Tom Walsh, Silvia Casadei, Ming K. Lee, Anne Thornton, Wendy Roeb, Sunday M. Stray, and Mary-Claire King, all of the UW Division of Medical Genetics, Department of Medicine, and Christopher Pennil, Kathy Agnew, Anneka Wickramanayake, Barbara Norquist, and Kathryn Pennington, all of the UW Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and Rochelle Garcia, UW Department of Pathology.

The study, “Mutations in 12 genes for inherited ovarian, Fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing,” was funded by the National Institutes of Health, The Breast Cancer Research Foundation, Susan G. Komen for the Cure, and the U.S. Department of Defense Ovarian Cancer Research Program.

Eurekalert University of Washington

NIH to Support Addiction Medicine Education Programs

Posted on by
Reply

Wednesday, October 26, 2011
Contact:NIAAA Press Office 301-443-3860

NIH grant will help translate addiction research into practice

A new grant will help establish a core of post-graduate addiction medicine education programs in academic medical centers throughout the United States. The National Infrastructure for Translating Addiction Research into Clinical Practice grant, awarded last month to the University at Buffalo School of Medicine and Biomedical Sciences, will provide about $900,000 over a two-year period. The grant was awarded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, and strengthens the foundation for training clinicians in the emerging specialty of addiction medicine.

“We are very excited about this opportunity to help medical students and residents in a variety of specialties who are interested in addiction medicine apply advances in research to real-world practice,” says NIAAA Acting Director Kenneth Warren, Ph.D. “This critical investment in our nation’s health will ultimately improve patient care and reduce the medical, social, and financial burden of the addiction disorders.”

“There is a shortage of academically oriented addiction medicine physicians qualified to conduct clinical research on addictions, to translate this research into practice, and to teach medical students and a wide range of residents about addiction in academic medical centers,” says Co-Principal Investigator Richard D. Blondell, M.D., professor of family medicine at the University at Buffalo, N.Y., and chair of the Residency Training and Accreditation Committee of the American Board of Addiction Medicine (ABAM) Foundation. “This grant will allow established leaders in addiction medicine to help bridge the gap between research and medical education on one hand and clinical practice on the other, and train a new cohort of leaders who will continue to advance the field.”

ABAM Foundation President-Elect Jeffrey Samet, M.D., professor of medicine and community health sciences at Boston University Schools of Medicine and Public Health, is also a co-principal investigator on the grant. In addition to Drs. Blondell and Samet, other key members of the ABAM Foundation will be actively involved in the project.

The goals of the project are to establish a National Addiction Medicine Residency Assistance Council (NAMRAC) that will develop standards of excellence for physician training; identify up to 10 addiction medicine model residency programs; and disseminate curricula and related products and recruit new members to NAMRAC so it can serve as an ongoing resource for development of additional addiction medicine residency programs.

The project is designed to rapidly deploy intensive assistance to the model residencies to help them overcome the barriers that frequently thwart new programs. The model residencies, in turn, will produce educational products, including research-to- practice physician education modules that can be used both in physician training and in helping practicing physicians to incorporate the latest knowledge from alcohol and addictions research into their patient care.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at www.niaaa.nih.gov.