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Lower Risk of Cancer for Women With BRCA1/2 Gene Mutations Seen With Prophylactic Surgeries

by Kathy Jones on September 2, 2010 at 9:23 PM
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 Lower Risk of Cancer for Women With BRCA1/2 Gene Mutations Seen With Prophylactic Surgeries

A study in the September 1 issue of JAMA says that women at increased risk of breast and ovarian cancer because of inherited mutations of the BRCA1 or BRCA2 genes who had prophylactic mastectomy or salpingo-oophorectomy had an associated decreased risk of breast cancer and ovarian cancer.

"Women who have inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes have substantially elevated risks of breast cancer and ovarian cancer, with a lifetime risk of breast cancer of 56 percent to 84 percent," the authors write. "Women who are mutation carriers have cancer risk-management options that include risk-reducing salpingo-oophorectomy, risk-reducing mastectomy, annual cancer screening, and chemoprevention."


Susan M. Domchek, M.D., of the University of Pennsylvania School of Medicine, Philadelphia, and colleagues conducted a study that included a large group of BRCA1/2 mutation carriers to determine cancer reduction estimates following risk-reducing salpingo-oophorectomy and mastectomy, incorporating mutation type (BRCA1 vs. BRCA2), and cancer history (prior history of breast cancer vs. none). The study, which included 2,482 women with BRCA1 or BRCA2 mutations (determined between 1974 and 2008), was conducted at 22 clinical and research genetics centers in Europe and North America. The women were followed up until the end of 2009.

The researchers found that risk-reducing mastectomy was associated with a decreased risk of breast cancer in BRCA1/2 mutation carriers, with no breast cancer events occurring in women who underwent risk-reducing mastectomy during 3 years of prospective follow-up. "In contrast, 7 percent of women without risk-reducing mastectomy over a similar follow-up period were diagnosed with breast cancer," the researchers write.

Risk-reducing salpingo-oophorectomy was associated with a decreased risk of ovarian cancer, with no ovarian cancer events seen during the 6 years of prospective follow-up in BRCA2 mutation carriers without prior breast cancer who underwent the procedure. Three percent of women without salpingo-oophorectomy over a similar follow-up period were diagnosed with ovarian cancer. No cases of ovarian cancer were diagnosed in BRCA2 mutation carriers after salpingo-oophorectomy, which was also associated with a decreased risk of breast cancer in both BRCA1 and BRCA2 mutation carriers without prior diagnosis of breast cancer.

"Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10 percent vs. 3 percent), breast cancer-specific mortality (6 percent vs. 2 percent), and ovarian cancer-specific mortality (3 percent vs. 0.4 percent)," according to the authors. (JAMA. 2010;304[9]:967-975. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Lessons Learned From Genetic Testing

Laura Esserman, M.D., M.B.A., of the University of California, San Francisco, and Virginia Kaklamani, M.D., D.Sc., of Northwestern University, Chicago, write in an accompanying editorial that the "discovery of biomarkers that identify high-risk individuals for a specific disease and integration of these biomarkers into clinical practice enables the systematic study of these populations—and development and testing of interventions to reduce their risk."

"The study by Domchek et al required more than 20 clinical centers collaborating to gather data in a standard fashion from the thousands of women who participated in the research. However, better mechanisms are needed to study and evaluate the introduction of new tests, like BRCA gene mutation testing, and to capture key pieces of de-identified information—such as the uptake of testing, results, clinical decisions, and outcomes—so that clinicians and researchers can continually learn from their experience. Measuring clinical outcomes should be a routine aspect of practice. As physicians begin to adopt computerized data-tracking systems, the goal of such systems should be both to facilitate the rapid introduction of innovations for care and to continually learn about the effects of new and established clinical practices."(JAMA. 2010;304[9]:1011-1012. Available pre-embargo to the media at www.jamamedia.org)

Source: Eurekalert

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