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Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations
Open accessAbstract
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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In an international longitudinal cohort of 4,332 women with P/LP BRCA1 or BRCA2 variants and no prior cancer, after mean follow-up of 9.0 years, the age-adjusted HR for all-cause mortality associated with preventive oophorectomy was 0.32 (95% CI 0.24-0.42; P < 0.001).
“After a mean follow-up of 9.0 years, the age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI: 0.24 - 0.42; P < 0.001).”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants (2026) · cites this paper as [55]
In that cohort, the age-adjusted HR for all-cause mortality associated with oophorectomy was 0.28 (95% CI 0.20-0.38; P < 0.001) for BRCA1 carriers and 0.43 (95% CI 0.22-0.90; P = 0.03) for BRCA2 carriers.
“The age-adjusted HR was 0.28 (95% CI: 0.20 - 0.38; P < 0.001) for women with BRCA1 and 0.43 (95% CI: 0.22 - 0.90; P = 0.03) for those with BRCA2 variant.”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants (2026) · cites this paper as [55]
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Research works printed but not linked: 27
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Abdel-Razeq, H., & Mansour, R. (2026) · World Journal of Oncology · doi:10.14740/wjon2692
Metadata
- Authors
- Kotsopoulos, J., Gronwald, J., Huzarski, T., Møller, P., Pal, T., McCuaig, J. M., Singer, C. F., Karlan, B. Y., Aeilts, A., Eng, C., Eisen, A., Bordeleau, L., Foulkes, W. D., Tung, N., Couch, F. J., Fruscio, R., Neuhausen, S. L., Zakalik, D., Cybulski, C., Metcalfe, K., Olopade, O. I., Sun, P., Lubinski, J., Narod, S. A., Hereditary Breast Cancer Clinical Study Group, Sweet, K., Elser, C., Wiesner, G., Poll, A., Kim, R., Armel, S. T., Demsky, R., Steele, L., Saal, H., Serfas, K., Panchal, S., Cullinane, C. A., Reilly, R. E., Rayson, D., Mercer, L., Cajal, T. R. Y., Dungan, J., Cohen, S., Lemire, E., Zovato, S., & Rastelli, A.
- Affiliations
- University of Toronto (CA)
- International Hereditary Cancer Center (PL)
- Oslo University Hospital (NO)
- Vanderbilt-Ingram Cancer Center (US)
- University Health Network (CA)
- Comprehensive Cancer Center Vienna (AT)
- University of California, Los Angeles (US)
- The Ohio State University Wexner Medical Center (US)
- Cleveland Clinic (US)
- Sunnybrook Health Science Centre (CA)
- Juravinski Cancer Centre (CA)
- McGill University (CA)
- Beth Israel Deaconess Medical Center (US)
- Mayo Clinic (US)
- University of Milano-Bicocca (IT)
- City of Hope (US)
- Oakland University (US)
- University of Chicago (US)
- International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
- for the Hereditary Breast Cancer Clinical Study Group
- Corresponding author
- Narod, Steven A.
- ORCID
- 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
- Narod, Steven A.
- Sweet, Kevin
- Elser, Christine
- Wiesner, Georgia
- Kim, Raymond
- Saal, Howard
- Rayson, Daniel
- Cohen, Stephanie
- Zovato, Stefania
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2024-04-01
- Volume
- 10
- Issue
- 4
- Pages
- 484
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC10905374
- OpenAlex
- W4392284556
- Cited by
- 56
- References
- 0
- Citations by year
- 2026: 25 · 2025: 24 · 2024: 7
- FWCI
- 14.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Cancer Institute (R35CA253187)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- bilateral oophorectomy, salpingectomy, BRCA1, BRCA2, hereditary breast and ovarian cancer, all-cause mortality, breast cancer-specific mortality, prophylactic surgery, ovarian cancer risk, breast cancer risk, peritoneal cancer, risk communication, informed consent
- MeSH terms
- Adult, Aged, Breast Neoplasms, Female, Humans, Longitudinal Studies, Male, Middle Aged, Mutation, Ovarian Neoplasms, Ovariectomy, Risk Management, Cohort Studies, BRCA1 Protein, BRCA2 Protein
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