Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.

Source

Kelly-Anne Phillips, Sue Anne McLachlan, Prue C. Weideman, and Kate Birch, Peter MacCallum Cancer Centre; Kelly-Anne Phillips, Roger L. Milne, Sue Anne McLachlan, Melissa C. Southey, and John L. Hopper, University of Melbourne; Sue Anne McLachlan, St Vincent's Hospital, Melbourne, Victoria; Michael L. Friedlander, Prince of Wales Hospital, Randwick, New South Wales, Australia; Roger L. Milne, Spanish National Cancer Research Centre; Trinidad Caldes, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain; Matti A. Rookus, Netherlands Cancer Institute, Amsterdam; Maartje Hooning and Caroline Seynaeve, Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam; Rob A.E.M. Tollenaar, Leiden University Medical Centre, Leiden, the Netherlands; Mary B. Daly, Fox Chase Cancer Center, Philadelphia, PA; Antonis C. Antoniou, Susan Peock, Debra Frost, Douglas F. Easton, Steve Ellis, University of Cambridge, Cambridge, United Kingdom; Saundra S. Buys and David Goldgar, Huntsman Cancer Institute at the University of Utah, UT; Nadine Andrieu and Dominique Stoppa-Lyonnet, Institut Curie; Nadine Andrieu, L'Institut National de la Santé et de la Recherche Médicale, U900; Dominique Stoppa-Lyonnet, L'Institut National de la Santé et de la Recherche Médicale, U830; Dominique Stoppa-Lyonnet, Université Paris-Descartes, Paris; Nadine Andrieu, Mines ParisTech, Fontainebleau; Catherine Noguès, Institut Curie, Hôpital René Huguenin, St Cloud; Valérie Bonadona, Université Lyon 1; Valérie Bonadona, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5558; Valérie Bonadona, Centre Léon Bérard, Lyon; Pascal Pujol, Centre Hospitalier Universitaire Arnaud de Villeneuve; Pascal Pujol, L'Institut National de la Santé et de la Recherche Médicale 896, Centre de Recherche en Cancérologie de Marseille Val d'Aurelle, Montpellier, France; Esther M. John, Cancer Prevention Institute of California, Fremont; Esther M. John, Stanford University School of Medicine, Stanford, CA; Mary Beth Terry, Columbia University, New York, NY; Irene L. Andrulis, University of Toronto, Toronto, Ontario; Jacques Simard, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada; Christian F. Singer, Medical University of Vienna, Vienna, Austria; Håkan Olsson, Lund University, Lund, Sweden; Anna Jakubowska, Pomeranian Medical University, Szczecin, Poland; Edith Olah, National Institute of Oncology, Budapest, Hungary; Anne-Marie Gerdes, Rigshospitalet and Copenhagen University, Copenhagen, Denmark; and Lenka Foretova, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

Abstract

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.