Yun-Hee Choi1, Mary Beth Terry2,3, Mary B Daly4, Robert J MacInnis5,6, John L Hopper5, Sarah Colonna7, Saundra S Buys7, Irene L Andrulis8,9, Esther M John10, Allison W Kurian10, Laurent Briollais8,11. 1. Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. 2. Mailman School of Public Health, Columbia University, New York, New York. 3. Herbert Irving Comprehensive Cancer Center, Columbia Irving Medical Center, New York, New York. 4. Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 5. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia. 6. Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, Victoria, Australia. 7. Department of Medicine and Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City. 8. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. 9. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. 10. Departments of Epidemiology & Population Health and of Medicine (Oncology), Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California. 11. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
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.
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.
Authors: Nan Huo; Carin Y Smith; Liliana Gazzuola Rocca; Walter A Rocca; Michelle M Mielke Journal: Am J Obstet Gynecol Date: 2021-11-10 Impact factor: 8.661
Authors: Ying L Liu; Kelsey Breen; Amanda Catchings; Megha Ranganathan; Alicia Latham; Deborah J Goldfrank; Rachel N Grisham; Kara Long Roche; Melissa K Frey; Dennis S Chi; Nadeem Abu-Rustum; Carol Aghajanian; Kenneth Offit; Zsofia K Stadler Journal: JCO Oncol Pract Date: 2021-09-28
Authors: Melanie W Hardy; Beth N Peshkin; Esther Rose; Mary Kathleen Ladd; Savannah Binion; Mara Tynan; Colleen M McBride; Karen A Grinzaid; Marc D Schwartz Journal: J Community Genet Date: 2022-04-29