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Clinical Management of BRCA Mutation Carriers


The peritoneum, however, appears to remain at low risk for the development of a Mullerian-type adenocarcinoma, even after oophorectomy.[170,171,172,173,174] Of the 324 women from the Gilda Radner Familial Ovarian Cancer Registry who underwent risk-reducing oophorectomy, six (1.8%) subsequently developed primary peritoneal carcinoma. No period of follow-up was specified.[175] Among 238 individuals in the Creighton Registry with BRCA1/BRCA2 mutations who underwent risk-reducing oophorectomy, five subsequently developed intra-abdominal carcinomatosis (2.1%). Of note, all five of these women had BRCA1 mutations.[176] A study of 1,828 women with a BRCA1 or BRCA2 mutation found a 4.3% risk of primary peritoneal cancer at 20 years after RRSO.[177]

Given the current limitations of screening for ovarian cancer and the high risk for the disease in BRCA1 and BRCA2 mutation carriers, NCCN Guidelines recommend RRSO between the ages of 35 and 40 years or upon completion of childbearing, as an effective risk-reduction option. Optimal timing of RRSO must be individualized, but evaluating a woman's risk for ovarian cancer based on mutation status can be helpful in the decision-making process. In a large study of U.S. BRCA1 and BRCA2 families, age-specific cumulative risk of ovarian cancer at age 40 years was 4.7% for BRCA1 mutation carriers and 1.9% for BRCA2 mutation carriers.[178] In a combined analysis of 22 studies of BRCA1 and BRCA2 mutation carriers, risk of ovarian cancer for BRCA1 mutation carriers increases most sharply from age 40 years to age 50 years, while for BRCA2 mutation carriers the risk is low before age 50 years, but increases sharply from age 50 years to age 60 years.[179] In a population-based study of BRCA mutations in ovarian cancer patients, patients with BRCA2 mutations had a significantly later age of onset than patients with BRCA1 mutations (57.3 years [range, 40-72] vs. 52.6 years [range, 31-78]).[180] In summary, women with BRCA1 mutations may consider RRSO for ovarian cancer risk reduction at a somewhat earlier age than women with BRCA2 mutations; however, women with BRCA2 mutations may still consider early RRSO for breast cancer risk reduction.

Studies indicate that removal of the uterus is not necessary as a risk-reducing procedure. No increased BRCA mutation prevalence was seen among 200 Jewish women with endometrial carcinoma or 56 unselected women with uterine papillary serous carcinoma.[167,168] However, small studies have reported that uterine papillary serous carcinoma may be part of the BRCA-associated spectrum of disease.[166,181,182] The cumulative risk of endometrial cancer among BRCA mutation carriers with ER-positive breast cancer treated with tamoxifen may be an additional factor to consider when counseling this population about prophylactic hysterectomy.[169,183] Hysterectomy might also be considered in young, unaffected BRCA mutation carriers who may want to use HRT but for whom hysterectomy would offer a simplified regimen of estrogen alone. In counseling a BRCA mutation carrier about optimal risk-reducing surgical options, aggregate data suggest that the risk from residual tubal tissue following RRSO is the least compelling reason to suggest hysterectomy.


WebMD Public Information from the National Cancer Institute

Last Updated: May 16, 2012
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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