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Original Investigation
February 25, 2021

Association of Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in Women With BRCA1 and BRCA2 Pathogenic Variants

Author Affiliations
  • 1Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
  • 2Mailman School of Public Health, Columbia University, New York, New York
  • 3Herbert Irving Comprehensive Cancer Center, Columbia Irving Medical Center, New York, New York
  • 4Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
  • 5Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia
  • 6Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia
  • 7Department of Medicine and Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City
  • 8Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada
  • 9Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
  • 10Departments of Epidemiology & Population Health and of Medicine (Oncology), Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California
  • 11Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
JAMA Oncol. 2021;7(4):585-592. doi:10.1001/jamaoncol.2020.7995
Key Points

Question  Is risk-reducing salpingo-oophorectomy associated with a reduction in breast cancer risk for women with pathogenic variants in the BRCA1 and BRCA2 genes?

Findings  In this case series of 876 families, risk-reducing salpingo-oophorectomy was associated with a reduced risk of breast cancer in women with BRCA1 and BRCA2 pathogenic variants within 5 years after surgery, with weaker association more than 5 years postsurgery. For BRCA1 and BRCA2 carriers who underwent risk-reducing salpingo-oophorectomy at age 40 years, the cumulative risk of breast cancer was 49.7% and 52.7%, respectively, by 70 years.

Meaning  Risk-reducing salpingo-oophorectomy was associated with a reduction in breast cancer risk for women carrying the BRCA1 and BRCA2 pathogenic gene variants, with a longer-term association with cumulative risk among women carrying BRCA1 pathogenic variants.

Abstract

Importance  Women with pathogenic variants in BRCA1 and BRCA2 are at high risk of developing breast and ovarian cancers. They usually undergo intensive cancer surveillance and may also consider surgical interventions, such as risk-reducing mastectomy or risk-reducing salpingo-oophorectomy (RRSO). Risk-reducing salpingo-oophorectomy has been shown to reduce ovarian cancer risk, but its association with breast cancer risk is less clear.

Objective  To assess the association of RRSO with the risk of breast cancer in women with BRCA1 and BRCA2 pathogenic variants.

Design, Setting, and Participants  This case series included families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried an inherited pathogenic variant in BRCA1 (498 families) or BRCA2 (378 families). A survival analysis approach was used that was designed specifically to assess the time-varying association of RRSO with breast cancer risk and accounting for other potential biases. Data were analyzed from August 2019 to November 2020.

Exposure  Risk-reducing salpingo-oophorectomy.

Main Outcomes and Measures  In all analyses, the primary end point was the time to a first primary breast cancer.

Results  A total of 876 families were evaluated, including 498 with BRCA1 (2650 individuals; mean [SD] event age, 55.8 [19.1] years; 437 White probands [87.8%]) and 378 with BRCA2 (1925 individuals; mean [SD] event age, 57.0 [18.6] years; 299 White probands [79.1%]). Risk-reducing salpingo-oophorectomy was associated with a reduced risk of breast cancer for BRCA1 and BRCA2 pathogenic variant carriers within 5 years after surgery (hazard ratios [HRs], 0.28 [95% CI, 0.10-0.63] and 0.19 [95% CI, 0.06-0.71], respectively), whereas the corresponding HRs were weaker after 5 years postsurgery (HRs, 0.64 [95% CI, 0.38-0.97] and 0.99 [95% CI; 0.84-1.00], respectively). For BRCA1 and BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years, the cause-specific cumulative risk of breast cancer was 49.7% (95% CI, 40.0-60.3) and 52.7% (95% CI, 47.9-58.7) by age 70 years, respectively, compared with 61.0% (95% CI, 56.7-66.0) and 54.0% (95% CI, 49.3-60.1), respectively, for women without RRSO.

Conclusions and Relevance  Although the primary indication for RRSO is the prevention of ovarian cancer, it is also critical to assess its association with breast cancer risk in order to guide clinical decision-making about RRSO use and timing. The results of this case series suggest a reduced risk of breast cancer associated with RRSO in the immediate 5 years after surgery in women carrying BRCA1 and BRCA2 pathogenic variants, and a longer-term association with cumulative breast cancer risk in women carrying BRCA1 pathogenic variants.

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