DOI: 10.1001/jamasurg.2026.4356 ISSN: 2168-6254

Projected Benefit of Bilateral Salpingo-Oophorectomy by Age in BRCA Carriers

Vasily Giannakeas, Adriana I. Apostol, Claudia Diella, Nupur Dave, Jacek Gronwald, Robert Fruscio, Beth Y. Karlan, Cezary Cybulski, Christian F. Singer, Pål Møller, Raymond H. Kim, Louise Bordeleau, Teresa Ramón y Cajal, Tuya Pal, Andrea Eisen, Fergus J. Couch, Dana Zakalik, Kelly Metcalfe, Nadine Tung, Amber Aeilts, Ping Sun, Jan Lubinski, Joanne Kotsopoulos, Steven A. Narod, , Kevin Sweet, Christine Elser, Seema Panchal, Georgia Wiesner, Susan Armel, Linda Steele, Howard Saal, Kim Serfas, Carey A Cullinane, Robert E Reilly, Daniel Rayson, Leanne Mercer, Jeffrey Dungan, Stephanie Cohen, Susan Neuhausen, Sophie Sun, Leigha Senter, Joanne L Blum, Klaudia Stempa, Willam Foulkes, Olufunmilayo Olopade, Edmond Lemire, Stefania Zovato, Antonella Rastelli, Michelle Jacobson, Tracy Graham, Intan Schraeder
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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.

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