Joanne Kotsopoulos1, Tomasz Huzarski2, Jacek Gronwald2, Christian F Singer3, Pal Moller4, Henry T Lynch5, Susan Armel6, Beth Karlan7, William D Foulkes8, Susan L Neuhausen9, Leigha Senter10, Nadine Tung11, Jeffrey N Weitzel12, Andrea Eisen13, Kelly Metcalfe14, Charis Eng15, Tuya Pal16, Gareth Evans17, Ping Sun1, Jan Lubinski2, Steven A Narod1. 1. Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada. 2. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 3. Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 4. Department for Medical Genetics, Inherited Cancer Research Group, and Department of Tumor Biology, Institute of Cancer Research, Norwegian Radium Hospital; Oslo University Hospital, Oslo, Norway. 5. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE. 6. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, ON, Canada. 7. Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, CA. 8. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada. 9. Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA. 10. Division of Human Genetics, The Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH. 11. Beth Israel Deaconess Medical Center, Boston, MA. 12. City of Hope National Medical Center, Duarte, CA. 13. Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada. 14. Faculty of Nursing, University of Toronto, ON, Canada. 15. Genomic Medicine Institute and Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH. 16. Moffitt Cancer Center, Departments of Cancer Epidemiology, Biostatistics, Anatomic Pathology, and Experimental Therapeutics, Tampa, FL. 17. Genomic Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK (GE).
Abstract
Background: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers. Methods: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided. Results: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51). Conclusions: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.
Background: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers. Methods: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided. Results: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51). Conclusions: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.
Authors: Jacek Gronwald; Andre Robidoux; Charmaine Kim-Sing; Nadine Tung; Henry T Lynch; William D Foulkes; Siranoush Manoukian; Peter Ainsworth; Susan L Neuhausen; Rochelle Demsky; Andrea Eisen; Christian F Singer; Howard Saal; Leigha Senter; Charis Eng; Jeffrey Weitzel; Pal Moller; Dawna M Gilchrist; Olufunmilayo Olopade; Ophira Ginsburg; Ping Sun; Tomasz Huzarski; Jan Lubinski; Steven A Narod Journal: Breast Cancer Res Treat Date: 2014-06-21 Impact factor: 4.872
Authors: B A M Heemskerk-Gerritsen; C Seynaeve; C J van Asperen; M G E M Ausems; J M Collée; H C van Doorn; E B Gomez Garcia; C M Kets; F E van Leeuwen; H E J Meijers-Heijboer; M J E Mourits; T A M van Os; H F A Vasen; S Verhoef; M A Rookus; M J Hooning Journal: J Natl Cancer Inst Date: 2015-03-18 Impact factor: 13.506
Authors: Joanne Kotsopoulos; Jan Lubinski; Henry T Lynch; Susan L Neuhausen; Parviz Ghadirian; Claudine Isaacs; Barbara Weber; Charmaine Kim-Sing; William D Foulkes; Ruth Gershoni-Baruch; Peter Ainsworth; Eitan Friedman; Mary Daly; Judy E Garber; Beth Karlan; Olufunmilayo I Olopade; Nadine Tung; Howard M Saal; Andrea Eisen; Michael Osborne; Hakan Olsson; Dawna Gilchrist; Ping Sun; Steven A Narod Journal: Cancer Causes Control Date: 2005-08 Impact factor: 2.506
Authors: Susan M Domchek; Tara M Friebel; Christian F Singer; D Gareth Evans; Henry T Lynch; Claudine Isaacs; Judy E Garber; Susan L Neuhausen; Ellen Matloff; Rosalind Eeles; Gabriella Pichert; Laura Van t'veer; Nadine Tung; Jeffrey N Weitzel; Fergus J Couch; Wendy S Rubinstein; Patricia A Ganz; Mary B Daly; Olufunmilayo I Olopade; Gail Tomlinson; Joellen Schildkraut; Joanne L Blum; Timothy R Rebbeck Journal: JAMA Date: 2010-09-01 Impact factor: 56.272
Authors: Nasim Mavaddat; Susan Peock; Debra Frost; Steve Ellis; Radka Platte; Elena Fineberg; D Gareth Evans; Louise Izatt; Rosalind A Eeles; Julian Adlard; Rosemarie Davidson; Diana Eccles; Trevor Cole; Jackie Cook; Carole Brewer; Marc Tischkowitz; Fiona Douglas; Shirley Hodgson; Lisa Walker; Mary E Porteous; Patrick J Morrison; Lucy E Side; M John Kennedy; Catherine Houghton; Alan Donaldson; Mark T Rogers; Huw Dorkins; Zosia Miedzybrodzka; Helen Gregory; Jacqueline Eason; Julian Barwell; Emma McCann; Alex Murray; Antonis C Antoniou; Douglas F Easton Journal: J Natl Cancer Inst Date: 2013-04-29 Impact factor: 13.506
Authors: Andrea Eisen; Jan Lubinski; Jan Klijn; Pal Moller; Henry T Lynch; Kenneth Offit; Barbara Weber; Tim Rebbeck; Susan L Neuhausen; Parviz Ghadirian; William D Foulkes; Ruth Gershoni-Baruch; Eitan Friedman; Gadi Rennert; Teresa Wagner; Claudine Isaacs; Charmaine Kim-Sing; Peter Ainsworth; Ping Sun; Steven A Narod Journal: J Clin Oncol Date: 2005-10-20 Impact factor: 44.544
Authors: Noah D Kauff; Susan M Domchek; Tara M Friebel; Mark E Robson; Johanna Lee; Judy E Garber; Claudine Isaacs; D Gareth Evans; Henry Lynch; Rosalind A Eeles; Susan L Neuhausen; Mary B Daly; Ellen Matloff; Joanne L Blum; Paul Sabbatini; Richard R Barakat; Clifford Hudis; Larry Norton; Kenneth Offit; Timothy R Rebbeck Journal: J Clin Oncol Date: 2008-02-11 Impact factor: 44.544
Authors: Olga Kim; Eun Young Park; Sun Young Kwon; Sojin Shin; Robert E Emerson; Yong-Hyun Shin; Francesco J DeMayo; John P Lydon; Donna M Coffey; Shannon M Hawkins; Lawrence A Quilliam; Dong-Joo Cheon; Facundo M Fernández; Kenneth P Nephew; Adam R Karpf; Martin Widschwendter; Anil K Sood; Robert C Bast; Andrew K Godwin; Kathy D Miller; Chi-Heum Cho; Jaeyeon Kim Journal: Proc Natl Acad Sci U S A Date: 2020-12-01 Impact factor: 11.205
Authors: C H Yip; D G Evans; G Agarwal; I Buccimazza; A Kwong; R Morant; I Prakash; C Y Song; N A Taib; C Tausch; O Ung; S Meterissian Journal: World J Surg Date: 2019-05 Impact factor: 3.352
Authors: George U Eleje; Ahizechukwu C Eke; Ifeanyichukwu U Ezebialu; Joseph I Ikechebelu; Emmanuel O Ugwu; Onyinye O Okonkwo Journal: Cochrane Database Syst Rev Date: 2018-08-24