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Clinical Management of BRCA Mutation Carriers


Viewed in the context of the criteria previously described,[130] this assay would be classified as phase 2 in its development. While this appears to be a promising avenue of ovarian cancer screening research, additional validation is required, particularly in an unselected population representative of the clinical screening population of interest. A recent position statement by the Society of Gynecologic Oncologists regarding this assay indicated "it is our opinion that additional research is needed to validate the test's effectiveness before offering it to women outside of the context of a research study conducted with appropriate informed consent under the auspices of an Institutional Review Board."

Level of evidence: 5

Risk-reducing surgery

Risk-reducing salpingo-oophorectomy

Numerous studies have found that women at inherited risk of breast and ovarian cancer have a decreased risk of ovarian cancer following risk-reducing salpingo-oophorectomy (RRSO). A retrospective study of 551 women with disease-associated BRCA1 or BRCA2 mutations found a significant reduction in risk of breast cancer (HR = 0.47; 95% CI, 0.29-0.77) and ovarian cancer (HR = 0.04; 95% CI, 0.01-0.16) after bilateral oophorectomy.[67] A prospective single-institution study of 170 women with BRCA1 or BRCA2 mutations showed a similar trend.[68] With oophorectomy, the HR was 0.15 (95% CI, 0.02-1.31) for ovarian, fallopian tube, or primary peritoneal cancer, and 0.32 (95% CI, 0.08-1.2) for breast cancer; the HR for either cancer was 0.25 (95% CI, 0.08-0.74). A prospective multicenter study of 1,079 women followed for a median of 30 to 35 months found that RRSO is highly effective in reducing ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. This study also showed that RRSO was associated with reductions in breast cancer risk for both BRCA1 and BRCA2 mutation carriers; however, the breast cancer risk reduction was more pronounced in BRCA2 carriers (HR = 0.28; 95% CI, 0.08-0.92).[69] In a case-control study in Israel, bilateral oophorectomy was associated with reduced ovarian/peritoneal cancer risks (OR = 0.12; 95% CI, 0.06-0.24).[146] A meta-analysis of all reports of RRSO and breast and ovarian/fallopian tube cancer in BRCA1/BRCA2 mutation carriers confirmed that RRSO was associated with a significant reduction in risk of ovarian or fallopian tube cancer (HR = 0.21, 95% CI, 0.12-0.39). The study also found a significant reduction in risk of breast cancer (overall HR = 0.49, 95% CI, 0.37-0.65; BRCA1 HR = 0.47, 95% CI, 0.35-0.64; BRCA2 HR = 0.47, 95% CI, 0.26-0.84).[70]

In addition to a reduction in risk of ovarian and breast cancer, RRSO may also significantly improve overall survival (OS) and breast and ovarian cancer-specific survival. A prospective cohort study of 666 women with germline mutations in BRCA1 and BRCA2 found an HR for overall mortality of 0.24 (95% CI, 0.08-0.71) in women who had RRSO compared with women who did not.[147] This study provides the first evidence to suggest a survival advantage among women undergoing RRSO.


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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