Originally published as JCO Early Release 10.1200/JCO.2007.11.1179 on July 16 2007

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Oral Contraceptives and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study: A Report From EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group

Richard M. Brohet, David E. Goldgar, Douglas F. Easton, Antonis C. Antoniou, Nadine Andrieu, Jenny Chang-Claude, Susan Peock, Rosalind A. Eeles, Margaret Cook, Carol Chu, Catherine Noguès, Christine Lasset, Pascaline Berthet, Hanne Meijers-Heijboer, Anne-Marie Gerdes, Håkan Olsson, Trinidad Caldes, Flora E. van Leeuwen, Matti A. Rookus

From the Netherlands Cancer Institute, Department of Epidemiology; Free University, Amsterdam; Erasmus University Hospital, Rotterdam, the Netherlands; International Agency for Research on Cancer, Department of Genetic Epidemiology; Centre Léon Bérard, Lyon; Institut National de la Santé et de la Recherche Médicale (INSERM) U794 et Service de Biostatistiques, Institut Curie, Paris; Centre René Huguenin, Saint Cloud; Centre François Baclesse, Caen, France; Department of Dermatology, University of Utah, School of Medicine, Salt Lake City, Utah; Department of Public Health and Primary Care, Genetic Epidemiology Unit, Cancer Research UK, University of Cambridge, Cambridge; Royal Marsden Hospital, London; Yorkshire Regional Genetics Service, Leeds, United Kingdom; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Odense University Hospital, Odense, Denmark; Lund University Hospital, Lund, Sweden; and the Hospital Clinico San Carlos, Madrid, Spain

Address reprint requests to Matti A. Rookus, PhD, Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, the Netherlands, e-mail: m.rookus{at}nki.nl

Purpose Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/2 carriers.

Patients and Methods In the International BRCA1/2 Carrier Cohort study (IBCCS), a retrospective cohort of 1,593 BRCA1/2 mutation carriers was analyzed with a weighted Cox regression analysis.

Results We found an increased risk of breast cancer for BRCA1/2 mutation carriers who ever used oral contraceptives (adjusted hazard ratio [HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full-term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers (4 or more years of use before first full-term pregnancy: HR = 1.49 [95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [95% CI, 1.21 to 5.49] for BRCA2 carriers).

Conclusion No evidence was found among BRCA1/2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full-term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.

published online ahead of print at www.jco.org on July 16, 2007.

Supported by National Institutes of Health Award CA81203 (D.G.); the Cancer Research United Kingdom (A.A.); and the Canadian Institutes of Health Research through the INHERIT BRCAs research program (D.F.E., D.G.). The EMBRACE study is supported by Cancer Research United Kingdom and The British Council and Health Research Board Research Visits Scheme; the IBCCS study has been supported by Grants No. SI2.328176 and SPC 2002482 from the Europe Against Cancer Programme of the European Commission; the GENEPSO study is supported by the Fondation de France and the Ligue Nationale Contre le Cancer; and the GEO-HEBON study is supported by the Dutch Cancer Society Grant No. NKI98-1854. D.F.E. is a Principal Research Fellow of Cancer Research United Kingdom.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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