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Prophylactic surgeries associated with lower risk of cancer for women with BRCA1/2 gene mutations

Date:
September 1, 2010
Source:
JAMA and Archives Journals
Summary:
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 (removal of the fallopian tubes and ovaries) had an associated decreased risk of breast cancer and ovarian cancer, according to a new study.

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 (removal of the fallopian tubes and ovaries) had an associated decreased risk of breast cancer and ovarian cancer, according to a study in the September 1 issue of JAMA.

"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.

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."


Story Source:

The above story is based on materials provided by JAMA and Archives Journals. Note: Materials may be edited for content and length.


Journal References:

  1. Susan M. Domchek; Tara M. Friebel; Christian F. Singer; D. Gareth Evans; Henry T. Lynch; Claudine Isaacs; Judy E. Garber; Susan L. Neuhausen; Ellen Matloff; Rosalind Eeles; Gabriella Pichert; Laura Van t'veer; Nadine Tung; Jeffrey N. Weitzel; Fergus J. Couch; Wendy S. Rubinstein; Patricia A. Ganz; Mary B. Daly; Olufunmilayo I. Olopade; Gail Tomlinson; Joellen Schildkraut; Joanne L. Blum; Timothy R. Rebbeck. Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality. JAMA, 2010; 304 (9): 967-975 [link]
  2. Laura Esserman; Virginia Kaklamani. Lessons Learned From Genetic Testing. JAMA, 2010; 304 (9): 1011-1012 [link]

Cite This Page:

JAMA and Archives Journals. "Prophylactic surgeries associated with lower risk of cancer for women with BRCA1/2 gene mutations." ScienceDaily. ScienceDaily, 1 September 2010. <www.sciencedaily.com/releases/2010/08/100831164926.htm>.
JAMA and Archives Journals. (2010, September 1). Prophylactic surgeries associated with lower risk of cancer for women with BRCA1/2 gene mutations. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2010/08/100831164926.htm
JAMA and Archives Journals. "Prophylactic surgeries associated with lower risk of cancer for women with BRCA1/2 gene mutations." ScienceDaily. www.sciencedaily.com/releases/2010/08/100831164926.htm (accessed July 22, 2014).

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