Association of Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in Women With <i>BRCA1</i> and <i>BRCA2</i> Pathogenic Variants
Authors: Yun-Hee Choi, Mary Beth Terry, Mary B. Daly, Robert J. MacInnis, John L. Hopper, Sarah Colonna, Saundra S. Buys, Irene L. Andrulis, Esther M. John, Allison W. Kurian, Laurent Briollais
Journal: JAMA Oncology (2021)

<h3>Importance</h3> Women with pathogenic variants in<i>BRCA1</i>and<i>BRCA2</i>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. <h3>Objective</h3> To assess the association of RRSO with the risk of breast cancer in women with<i>BRCA1</i>and<i>BRCA2</i>pathogenic variants. <h3>Design, Setting, and Participants</h3> This case series included families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried an inherited pathogenic variant in<i>BRCA1</i>(498 families) or<i>BRCA2</i>(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. <h3>Exposure</h3> Risk-reducing salpingo-oophorectomy. <h3>Main Outcomes and Measures</h3> In all analyses, the primary end point was the time to a first primary breast cancer. <h3>Results</h3> A total of 876 families were evaluated, including 498 with<i>BRCA1</i>(2650 individuals; mean [SD] event age, 55.8 [19.1] years; 437 White probands [87.8%]) and 378 with<i>BRCA2</i>(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<i>BRCA1</i>and<i>BRCA2</i>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<i>BRCA1</i>and<i>BRCA2</i>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. <h3>Conclusions and Relevance</h3> 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<i>BRCA1</i>and<i>BRCA2</i>pathogenic variants, and a longer-term association with cumulative breast cancer risk in women carrying<i>BRCA1</i>pathogenic variants.