Joanne Kotsopoulos1,2, Jan Lubinski3, Henry T Lynch4, Nadine Tung5, Susan Armel6, Leigha Senter7, Christian F Singer8, Robert Fruscio9, Fergus Couch10, Jeffrey N Weitzel11, Beth Karlan12, William D Foulkes13, Pal Moller14, Andrea Eisen15, Peter Ainsworth16, Susan L Neuhausen17, Olufunmilayo Olopade18, Ping Sun1, Jacek Gronwald3, Steven A Narod19,20. 1. Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6th Floor, Toronto, ON, M5S 1B2, Canada. 2. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 3. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 4. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA. 5. Beth Israel Deaconess Medical Center, Boston, MA, USA. 6. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada. 7. Division of Human Genetics, Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH, USA. 8. Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 9. Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy. 10. Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 11. Division of Clinical Cancer Genomics, Department of Population Sciences, City of Hope, Duarte, CA, USA. 12. Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA. 13. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, QC, Canada. 14. Inherited Cancer Research Group, Department for Medical Genetics, Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. 15. Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada. 16. Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada. 17. Division of Biomarkers of Early Detection and Prevention, Department of Population Science, City of Hope, Duarte, CA, USA. 18. Department of Medicine and Human Genetics, University of Chicago, Chicago, IL, USA. 19. Women's College Research Institute, Women's College Hospital, 76 Grenville St., 6th Floor, Toronto, ON, M5S 1B2, Canada. steven.narod@wchospital.ca. 20. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. steven.narod@wchospital.ca.
Abstract
PURPOSE: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. METHODS: Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). RESULTS: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68-1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). CONCLUSION: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer.
PURPOSE: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. METHODS:Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). RESULTS: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68-1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). CONCLUSION: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer.
Entities:
Keywords:
BRCA1/2; Contralateral breast cancer; Oophorectomy