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

Lieske H Schrijver (1) , Håkan Olsson (2) , Kelly-Anne Phillips (3, 4) , Mary Beth Terry (5) , David E Goldgar (6) , Karin Kast (7) , Christoph Engel (8, 9) , Thea M Mooij (1) , Julian Adlard (10) , Daniel Barrowdale (11) , Rosemarie Davidson (12) , Ros Eeles (13) , Steve Ellis (11) , D Gareth Evans (14) , Debra Frost (11) , Louise Izatt (15) , Mary E Porteous (16) , Lucy E Side (17) , Lisa Walker (18) , Pascaline Berthet (19) , Valérie Bonadona (20) , Dominique Leroux (21, 22) , Emmanuelle Mouret-Fourme (23) , Laurence Venat-Bouvet (24) , Saundra S Buys (25) , Melissa C Southey (26) , Esther M John (27, 28) , Wendy K Chung (29) , Mary B Daly (30) , Anita Bane (31, 32) , Christi J van Asperen (33) , Encarna B Gómez Garcia (34) , Marian J E Mourits (35) , Theo a M van Os (36) , Marie-José Roos-Blom (1) , Michael L Friedlander (37, 38) , Sue-Anne Mclachlan (4, 39) , Christian F Singer (40) , Yen y Tan (40) , Lenka Foretova (41) , Marie Navratilova (41, 42) , Anne-Marie Gerdes (43) , Trinidad Caldes (44) , Jacques Simard (45) , Edith Olah (46) , Anna Jakubowska (47) , Brita Arver (32) , Ana Osorio (48) , Catherine Noguès (49) , Nadine Andrieu (50) , Douglas F Easton (11) , Flora E van Leeuwen (1) , John L Hopper (4) , Roger L Milne (4, 51) , Antonis C Antoniou (11) , Matti A Rookus (1)

1 NKI - Netherlands Cancer Institute
2 Skane University Hospital [Lund]
3 Lund University [Lund]
4 University of Melbourne
5 Columbia Mailman School of Public Health
6 University of Utah School of Medicine [Salt Lake City]
7 TU Dresden - Technische Universität Dresden = Dresden University of Technology
8 Department of Clinical Sciences [Lund]
9 Leipzig University
10 Chapel Allerton Hospital
11 CAM - University of Cambridge [UK]
12 Queen Elizabeth University Hospital (Glasgow)
13 Royal Marsden NHS Foundation Trust
14 University of Manchester [Manchester]
15 Guy's and St Thomas NHS Foundation Trust [London]
16 Western General Hospital [Edinburgh, UK]
17 GOSHC - Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK]
18 Churchill Hospital [Breast Care Unit]
19 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
20 UCBL - Université Claude Bernard Lyon 1
21 CHU - Centre Hospitalier Universitaire [Grenoble]
22 hôpital couple-enfant [CHU Grenoble Alpes]
23 Hôpital René HUGUENIN (Saint-Cloud)
24 Hôpital Dupuytren [CHU Limoges]
25 Huntsman Cancer Institute [Salt Lake City]
26 Monash University [Melbourne]
27 Stanford University School of Medicine [CA, USA]
28 California Sciences Institute
29 Columbia University [New York]
30 Fox Chase Cancer Center
31 McMaster University [Hamilton, Ontario]
32 Karolinska Institutet [Stockholm]
33 Leiden University Medical Center (LUMC)
34 GROW - School for Oncology and Developmental Biology [Maastricht]
35 UMCG - University Medical Center Groningen [Groningen]
36 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
37 UNSW - University of New South Wales [Sydney]
38 Prince of Wales Hospital
39 St. Vincent's Hospital, Sydney
40 Medizinische Universität Wien = Medical University of Vienna
41 RECAMO - Masaryk Memorial Cancer Institute
42 University Hospital of Cologne [Cologne]
43 Copenhagen University Hospital
44 IdISSC - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain]
45 ULaval - Université Laval [Québec]
46 National Institute of Oncology [Budapest, Hungary]
47 PUM - Pomeranian Medical University [Szczecin]
48 Spanish National Cancer Centre
49 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
50 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
51 Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia]

Background: For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods: Breast 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. Results: For 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). Conclusions: Prospective 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.

Domaines: Sciences du Vivant [q-bio]

Lieske H Schrijver, Håkan Olsson, Kelly-Anne Phillips, Mary Beth Terry, David E Goldgar, et al.. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study. JNCI Cancer Spectrum, 2021, 2 (2), pky023. ⟨10.1093/jncics/pky023⟩. ⟨inserm-03342591⟩