Joanne Kotsopoulos1,2, Jacek Gronwald3, Beth Y Karlan4, Tomasz Huzarski3, Nadine Tung5, Pal Moller6, Susan Armel7, Henry T Lynch8, Leigha Senter9, Andrea Eisen10, Christian F Singer11, William D Foulkes12, Michelle R Jacobson1, Ping Sun1, Jan Lubinski3, Steven A Narod1,2. 1. Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada. 2. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. 3. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. 4. Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, California. 5. Beth Israel Deaconess Medical Center, Boston, Massachusetts. 6. Inherited Cancer Research Group, The Norwegian Radium Hospital, Department for Medical Genetics, Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital; Oslo University Hospital, Oslo, Norway. 7. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Ontario, Canada. 8. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska. 9. Division of Human Genetics, the Ohio State University Medical Center, Comprehensive Cancer Center, Columbus. 10. Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada. 11. Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 12. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada.
Abstract
Importance: Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. Objective: To determine the association between HRT use and BRCA1-associated breast cancer. Design, Setting, and Participants: A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. Exposures: A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. Main Outcomes and Measures: Incident breast cancer. Results: A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). Conclusions and Relevance: These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.
Importance: Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. Objective: To determine the association between HRT use and BRCA1-associated breast cancer. Design, Setting, and Participants: A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. Exposures: A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. Main Outcomes and Measures: Incident breast cancer. Results: A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). Conclusions and Relevance: These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.
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: Wendy Y Chen; Susan E Hankinson; Stuart J Schnitt; Bernard A Rosner; Michelle D Holmes; Graham A Colditz Journal: Cancer Date: 2004-10-01 Impact factor: 6.860
Authors: Cathleen M Rivera; Brandon R Grossardt; Deborah J Rhodes; Robert D Brown; Véronique L Roger; L Joseph Melton; Walter A Rocca Journal: Menopause Date: 2009 Jan-Feb Impact factor: 2.953
Authors: Kelly A Metcalfe; Daphna Birenbaum-Carmeli; Jan Lubinski; Jacek Gronwald; Henry Lynch; Pal Moller; Parviz Ghadirian; William D Foulkes; Jan Klijn; Eitan Friedman; Charmaine Kim-Sing; Peter Ainsworth; Barry Rosen; Susan Domchek; Teresa Wagner; Nadine Tung; Siranoush Manoukian; Fergus Couch; Ping Sun; Steven A Narod Journal: Int J Cancer Date: 2008-05-01 Impact factor: 7.396
Authors: Verena Sigl; Kwadwo Owusu-Boaitey; Purna A Joshi; Anoop Kavirayani; Gerald Wirnsberger; Maria Novatchkova; Ivona Kozieradzki; Daniel Schramek; Nnamdi Edokobi; Jerome Hersl; Aishia Sampson; Ashley Odai-Afotey; Conxi Lazaro; Eva Gonzalez-Suarez; Miguel A Pujana; For Cimba; Holger Heyn; Enrique Vidal; Jennifer Cruickshank; Hal Berman; Renu Sarao; Melita Ticevic; Iris Uribesalgo; Luigi Tortola; Shuan Rao; Yen Tan; Georg Pfeiler; Eva Yhp Lee; Zsuzsanna Bago-Horvath; Lukas Kenner; Helmuth Popper; Christian Singer; Rama Khokha; Laundette P Jones; Josef M Penninger Journal: Cell Res Date: 2016-05-31 Impact factor: 25.617
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: Kathryn A Mills; Tanvi V Joshi; Lindsay West; Michelle Kuznicki; Laura Kent; Alexis N Hokenstad; James C Cripe; Candice Woolfolk; Leigha Senter; Jamie N Bakkum-Gamez; Robert M Wenham; David E Cohn; Victoria Bae-Jump; Premal H Thaker Journal: Gynecol Oncol Date: 2020-03-03 Impact factor: 5.482
Authors: Phuong L Mai; Helen Q Huang; Lari B Wenzel; Paul K Han; Richard P Moser; Gustavo C Rodriguez; John Boggess; Thomas J Rutherford; David E Cohn; Noah D Kauff; Kelly-Anne Phillips; Kelly Wilkinson; Robert M Wenham; Chad Hamilton; Matthew A Powell; Joan L Walker; Mark H Greene; Martee L Hensley Journal: Gynecol Oncol Date: 2019-11-21 Impact factor: 5.482
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