Phuong L Mai1, Austin Miller2, Mitchell H Gail3, Steven Skates4, Karen Lu5, Mark E Sherman6, Olga B Ioffe7, Gustavo Rodriguez8,9, David E Cohn10, John Boggess11, Thomas Rutherford12, Noah D Kauff13, Janet S Rader14, Kelly-Anne Phillips15,16, Paul A DiSilvestro17, Alexander B Olawaiye18, Mildred R Ridgway19, Mark H Greene1, Marion Piedmonte2, Joan L Walker20. 1. Clinical Genetics Branch, National Cancer Institute, Rockville, MD. 2. NRG Oncology, Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY. 3. Biostatistics Branch, National Cancer Institute, Rockville, MD. 4. Department of Biostatistics Unit, Massachusetts General Hospital, Boston, MA. 5. Department of GYN Oncology, MD Anderson Cancer Center, Houston, TX. 6. Division of Cancer Epidemiology and Genetics, and Environmental Epidemiology Branch, National Cancer Institute, Rockville, MD. 7. Department of Pathology, University of Maryland Medical Center, Baltimore, MD. 8. Division of Gynecologic Oncology, NorthShore University Health System, Evanston, IL. 9. Department of Obstetrics and Gynecology, University of Chicago, Evanston, IL. 10. Division of Gynecologic Oncology, Ohio State University, Columbus, OH. 11. Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Raleigh, NC. 12. Department of Gynecologic Oncology, Yale University, Norwalk, CT. 13. Gynecology and Clinical Genetics Services, Memorial Sloan Kettering Cancer Center, New York, NY. 14. Division of Gynecologic Oncology, Medical College of Wisconsin, Milwaukee, WI. 15. Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 16. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia. 17. Department of Obstetrics & Gynecology, Women & Infants Hospital, Providence, RI. 18. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital of UPMC, Pittsburgh, PA. 19. OB/GYN, University of MS Medical Center, Jackson, MS. 20. Department of OB/GYN, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Abstract
BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. METHODS: We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. RESULTS: The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval = 0.45 to 1.67; P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. CONCLUSIONS: These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention. Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.
BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. METHODS: We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. RESULTS: The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval = 0.45 to 1.67; P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. CONCLUSIONS: These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention. Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.
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