Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations
Authors: Kotsopoulos Joanne , Gronwald Jacek , Huzarski Tomasz , Møller Pål , Pal Tuya , McCuaig Jeanna M. , Singer Christian F. , Karlan Beth Y. , Aeilts Amber , Eng Charis , Eisen Andrea , Bordeleau Louise , Foulkes William D. , Tung Nadine , Couch Fergus J. , Fruscio Robert , Neuhausen Susan L. , Zakalik Dana , Cybulski Cezary , Metcalfe Kelly , Olopade Olufunmilayo I. , Sun Ping , Lubinski Jan , Narod Steven A. ,   Hereditary Breast Cancer Clinical Study Group, Sweet Kevin , Elser Christine , Wiesner Georgia , Poll Aletta , Kim Raymond , Armel Susan T. , Demsky Rochelle , Steele Linda , Saal Howard , Serfas Kim , Panchal Seema , Cullinane Carey A. , Reilly Robert E. , Rayson Daniel , Mercer Leanne , Cajal Teresa Ramon y , Dungan Jeffrey , Cohen Stephanie , Lemire Edmond , Zovato Stefania , Rastelli Antonella 
Published: February 2024

ImportancePreventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.ObjectiveTo evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.Design, Setting, and ParticipantsIn this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.ExposuresSelf-reported bilateral oophorectomy (with or without salpingectomy).Main Outcomes and MeasuresAll-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.ResultsThere were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P &amp;lt; .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P &amp;lt; .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy.Conclusions and RelevanceIn this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.