Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

JNCI Cancer Spectrum

Terry, Mary Beth¹  Southey, Melissa C²  Venat-Bouvet, Laurence³  Walker, Lisa⁴  Evans, D Gareth⁴  Porteous, Mary E⁴  Kast, Karin⁵  Berthet, Pascaline⁶  Easton, Douglas F⁷  Andrieu, Nadine⁷  Hopper, John L⁸  Tan, Yen Y⁹  Navratilova, Marie^1,10  Singer, Christian F^1,11  Frost, Debra^1,12  Mooij, Thea M^1,13  Engel, Christoph^1,14  Gómez Garcia, Encarna B^1,15  Gerdes, Anne-Marie^1,16  Schrijver, Lieske H^1,16  Eeles, Ros^1,16  Foretova, Lenka^1,18  Adlard, Julian^1,19  Simard, Jacques^2,20  Arver, Brita^2,21  Daly, Mary B^2,22  Olah, Edith^2,23  Rookus, Matti A^2,24  Noguès, Catherine^2,25  Osorio, Ana^2,25  Olsson, Håkan^2,26  McLachlan, Sue-Anne^2,27  Friedlander, Michael L^2,28  van Os, Theo A M^2,29  Jakubowska, Anna^3,30  Goldgar, David E^3,30  Roos-Blom, Marie-José^3,31  Bane, Anita^3,32  Side, Lucy E^3,33  Antoniou, Antonis C^3,34  Chung, Wendy K^3,35  Davidson, Rosemarie^3,36  Phillips, Kelly-Anne^3,37  van Leeuwen, Flora E^3,38  Milne, Roger L^3,39  Leroux, Dominique^4,40  Izatt, Louise^4,41  Barrowdale, Daniel^4,42  Mouret-Fourme, Emmanuelle^4,43  van Asperen, Christi J^4,44  Caldes, Trinidad^4,45  John, Esther M^4,46  Bonadona, Valérie^4,47  Mourits, Marian J E^4,48  Buys, Saundra S^4,49  Ellis, Steve^5,50 

[1]Sir Peter MacCallum Department of Oncology

[2]CHU de Grenoble, Hôpital Couple-Enfant, Département de Génétique, Grenoble, France

[3]Centre François Baclesse, Caen, France

[4]Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK

[5]Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia

[6]Clinical Genetics, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK

[7]Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology

[8]Department of Clincial Genetics, Rigshospitalet, København, Denmark

[9]Department of Clinical Genetics and GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands

[10]Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands

[11]Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands

[12]Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, UK

[13]Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT

[14]Department of Epidemiology

[15]Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA

[16]Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands

[17]Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland

[18]Department of Gynaecologic Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

[19]Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany

[20]Department of Medical Oncology, Prince of Wales Hospital, Randwick, Australia

[21]Department of Medical Oncology, St Vincent's Hospital, Fitzroy, Australia

[22]Department of Medicine, Huntsman Cancer Institute, Salt Lake City, UT

[23]Department of Medicine, St. Vincent’s Hospital, University of Melbourne, Parkville, Victoria, Australia

[24]Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary

[25]Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

[26]Department of Oncology, Lund University Hospital

[27]Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

[28]Department of Pathology and Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, Hamilton, Ontario, Canada

[29]Department of Pediatrics and Medicine, Columbia University, New York, NY

[30]Division of Cancer Medicine

[31]Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA

[32]Genetic Epidemiology Laboratory, Department of Pathology

[33]Genomic Medicine, Manchester Academic Health Sciences Centre, Institute of Human Development, Manchester University, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK

[34]Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, Quebec, Canada

[35]Hôpital Universitaire Dupuytren, Service d’Oncologie Médicale, Limoges, France

[36]Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany

[37]Lund University, Lund, Sweden

[38]Medical Faculty, University of Cologne and University Hospital Cologne, Germany

[39]Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, CIBERONC, Martin Lagos s/n, Madrid, Spain

[40]North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, UK

[41]Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK

[42]Oncology and Pathology, Department of Clinical Sciences Lund

[43]Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK

[44]Precision Medicine, School of Clinical Science at Monash Health, Monash University, Victoria, Australia

[45]Prince of Wales Clinical School, University of New South Wales, Sydney, Australia

[46]Service de Génétique Oncologique, Hôpital René Huguenin/Institut Curie, Saint-Cloud, France

[47]South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK

[48]Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA

[49]Université Claude Bernard Lyon 1, Villeurbanne, France

[50]Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK

关键词: oral contraceptives;    brca1 protein;    brca1 gene;    breast cancer;    brca1 mutation;    brca2 mutation;    mutation;    breast cancer risk;    brca2 gene;    brca2 protein;    pregnancy;    breast;    contraceptive methods;    middle-aged adult;   

DOI  :  10.1093/jncics/pky023

学科分类：肿瘤学

来源: Oxford University Press

【 摘 要 】

BackgroundFor BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear.MethodsBreast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed.ResultsFor BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002).ConclusionsProspective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.

【 授权许可】

CC BY-NC-ND