Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation

• DOI: 10.1007/s10549-023-06991-3
• Publication Date: 2023-07-11T07:02:06Z
• Authors: Joanne Kotsopoulos; Jacek Gronwald; Tomasz Huzarski; Amber Aeilts; Susan Randall Armel; Beth Karlan; Christian F. Singer; Andrea Eisen; Nadine Tung; Olufunmilayo Olopade; Louise Bordeleau; Charis Eng; William D. Foulkes; Susan L. Neuhausen; Carey A. Cullinane; Tuya Pal; Robert Fruscio; Jan Lubinski; Kelly Metcalfe; Ping Sun; Steven A. Narod; ; Georgia Wiesner; Aletta Poll; Raymond Kim; Jeanna McCuaig; Dana Zakalik; Fergus Couch; Linda Steele; Howard Saal; Edmond Lemire; Kim Serfas; Kevin Sweet; Seema Panchal; Christine Elser; Robert E Reilly; Joanne L Blum; Cezary Cybulski; Daniel Rayson; Teresa y Cajal Ramón; Jeffrey Dungan; Stefania Zovato; Antonella Rastelli; Pal Moller; Stephanie Cohen
• Keywords: Aging; Oncology and Carcinogenesis; Clinical Sciences; Genes, BRCA1; Clinical sciences; Breast Neoplasms; Chemoprevention; Breast cancer; Risk Factors; Breast Cancer; Genetics; 2.2 Factors relating to the physical environment; Humans; Oncology & Carcinogenesis; Aetiology; BRCA1; BRCA2; Breast cancer; Chemoprevention; Raloxifene; Tamoxifen;; Cancer; BRCA2 Protein; Biomedical and Clinical Sciences; BRCA1 Protein; Prevention; Oncology and carcinogenesis; BRCA1; BRCA2; and the Hereditary Breast Cancer Clinical Study Group; Tamoxifen; Genes; Raloxifene Hydrochloride; Mutation; Female; Raloxifene

Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation.We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07).Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.