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. 2024 Apr 1;10(4):484-492.
doi: 10.1001/jamaoncol.2023.6937.

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Joanne Kotsopoulos  1   2 , Jacek Gronwald  3 , Tomasz Huzarski  3 , Pål Møller  4 , Tuya Pal  5 , Jeanna M McCuaig  6   7 , Christian F Singer  8 , Beth Y Karlan  9 , Amber Aeilts  10 , Charis Eng  11 , Andrea Eisen  12 , Louise Bordeleau  13 , William D Foulkes  14 , Nadine Tung  15 , Fergus J Couch  16 , Robert Fruscio  17 , Susan L Neuhausen  18 , Dana Zakalik  19 , Cezary Cybulski  3 , Kelly Metcalfe  1   20 , Olufunmilayo I Olopade  21 , Ping Sun  1 , Jan Lubinski  3 , Steven A Narod  1   2 ; Hereditary Breast Cancer Clinical Study Group
Collaborators, Affiliations

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Joanne Kotsopoulos et al. JAMA Oncol. .

Abstract

Importance: Preventive 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.

Objective: To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.

Design, setting, and participants: In 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.

Exposures: Self-reported bilateral oophorectomy (with or without salpingectomy).

Main outcomes and measures: All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

Results: There 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 < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .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 relevance: In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pal reported serving on a scientific/medical advisory board for Natera outside the submitted work. Dr McCuaig reported personal fees from AstraZeneca and Merck outside the submitted work. Dr Karlan reported grants from American Cancer Society during the conduct of the study. Prof Couch reported grants from National Institutes of Health (R35CA253187) during the conduct of the study; and grants from GRAIL and personal fees from Ambry Genetics and AstraZeneca outside the submitted work. Dr Olopade reported being a cofounder of CancerIQ, serving on a scientific advisory board for Tempus, and serving on the board for 54gene outside the submitted work. No other disclosures were reported.

Comment in

References

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