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Phillips KA , Milne RL , Rookus MA , Daly MB , Antoniou AC , Peock S , Frost D , Easton DF , Ellis S , Friedlander ML , Buys SS , Andrieu N , Nogues C , Stoppa-Lyonnet D , Bonadona V , Pujol P , McLachlan SA , John EM , Hooning MJ , Seynaeve C , Tollenaar RA , Goldgar DE , Terry MB , Caldes T , Weideman PC , Andrulis IL , Singer CF , Birch K , Simard J , Southey MC , Olsson HL , Jakubowska A , Olah E , Gerdes AM , Foretova L , Hopper JL
Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
J Clin Oncol. 2013 Sep 1;31(25) :3091-3099
PMID: 23918944    PMCID: PMC 3753701   
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PURPOSE: To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. METHODS: Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. RESULTS: Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases). CONCLUSION: This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
Phillips, Kelly-Anne Milne, Roger L Rookus, Matti A Daly, Mary B Antoniou, Antonis C Peock, Susan Frost, Debra Easton, Douglas F Ellis, Steve Friedlander, Michael L Buys, Saundra S Andrieu, Nadine Nogues, Catherine Stoppa-Lyonnet, Dominique Bonadona, Valerie Pujol, Pascal McLachlan, Sue Anne John, Esther M Hooning, Maartje J Seynaeve, Caroline Tollenaar, Rob A E M Goldgar, David E Terry, Mary Beth Caldes, Trinidad Weideman, Prue C Andrulis, Irene L Singer, Christian F Birch, Kate Simard, Jacques Southey, Melissa C Olsson, Hakan L Jakubowska, Anna Olah, Edith Gerdes, Anne-Marie Foretova, Lenka Hopper, John L Journal of clinical oncology : official journal of the American Society of Clinical Oncology J Clin Oncol. 2013 Sep 1;31(25):3091-3099. Epub 2013 Aug 5.