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Importance Women with a BRCA1 or BRCA2 variant face a high lifetime risk of ovarian cancer and are often advised to undergo preventive surgery (bilateral salpingo-oophorectomy [BSO]) before cancer develops. The recommended age of BSO is 35 years for BRCA1 carriers and is 45 years for BRCA2 carriers, but some women choose to delay surgery until the age of menopause; there is no standard upper age at which surgery is no longer advised.
Objective To estimate the residual lifetime risk of ovarian cancer among BRCA carriers by current age and projected age at BSO.
Design, Setting, and Participants This was a prospective cohort study in an international cohort of BRCA carriers monitored for incident ovarian cancer. A life table analysis used age-specific ovarian cancer incidence rates and competing mortality rates to estimate lifetime risk of ovarian cancer among women with a BRCA1 or BRCA2 pathogenic variant with both ovaries intact and no prior ovarian cancer at baseline. Patients were recruited between 1995 and 2024 across 24 international centers, and the mean (SD) follow-up was 4.4 (3.9) years.
Exposure Timing of BSO, defined as immediate BSO, delayed BSO, or no BSO.
Main Outcome and Measures Residual lifetime risk of ovarian cancer.
Results The cohort consisted of 4286 BRCA1 and 1427 BRCA2 carriers between the ages of 30 and 74 years at baseline (mean [SD] age, 42.0 [10.8] years). There were 249 incident ovarian cancers in the follow-up period. The lifetime risk of ovarian cancer was 55.0% (95% CI, 48.8-61.9) for a BRCA1 carrier and 24.1% (95% CI, 15.1-36.6) for a BRCA2 carrier. A 30-year-old BRCA1 carrier with BSO delayed to age 50 years had a projected residual ovarian cancer risk of 23.9% (95% CI, 20.7-27.4). At age 75 years, the residual risk of ovarian cancer was estimated to be 8.4% (95% CI, 1.7-22.7) for a BRCA1 carrier and 3.7% (95% CI, 0.1-22.7) for a BRCA2 carrier.
Conclusions and Relevance The residual risk of ovarian cancer for older women in good health is sufficiently high to consider preventive surgery. BRCA1 carriers who defer BSO until age 50 years may face a substantial risk of developing ovarian cancer.
Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased riskfor breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases.
OBJECTIVE:
To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer.
EVIDENCE REVIEW:
The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery.
FINDINGS:
For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate.
CONCLUSIONS AND RECOMMENDATION:
The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation).
