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

EMBRACE, GENEPSO, BCFR, HEBON, kConFab, and IBCCS

doi:10.1093/jncics/pky023

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

EMBRACE, GENEPSO, BCFR, HEBON, kConFab, and IBCCS

Cancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, the Netherlands; Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD, Rotterdam, the Netherlands; Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.
Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Sremska, Serbia
Department of Clinical Sciences, Pediatric Nephrology, Skåne University Hospital, Lund University, Lund, Sweden.
MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
University of Utah School of Medicine
Medical Faculty and University Hospital Carl Gustav Carus
NASU - Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
Chapel Allerton Hospital
Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK; NIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge CB2 0QQ UK.
South Glasgow University Hospitals
The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom
Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals, NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9WL, UK; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9NT, UK.
Department of Clinical Genetics, Harvey Institute for Human Genetics, 6701 Charles St, Towson, MD 21204, USA
North Western Health Board Sligo General Hospital
Great Ormond Street Hospital for Children NHS Trust
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, United Kingdom.
Centre François Baclesse
Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
CHU Grenoble Alpes, Service Universitaire Pneumologie Physiologie, Université Grenoble Alpes, Grenoble, France.
Service de Génétique Oncologique
Hôpital Universitaire Dupuytren
Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, USA.
Genetic Epidemiology Laboratory
Cancer Prevention Institute of California
Columbia University
Fox Chase Cancer Center
McMaster University
Center Proteomics Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
Maastricht University Medical Center +, part of the Nijmegen/Eindhoven/Maastricht Haemophilia Treatment Center (HTC).
Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
NKI
University of New South Wales
Department of Physiology, University of Melbourne, Melbourne, Australia.
Division of Cardiac, Thoracic, Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria.
Masaryk Memorial Cancer Institute
Danish PCD Centre, Pediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark , Copenhagen, Denmark.
Hospital Clínico San Carlos
Centre Hospitalier Universitaire de Québec Research Center and Laval University
National Institute of Oncology
Pomeranian Medical University in Szczecin
Karolinska Institutet and Karolinska University Hospital
Amsterdam UMC - Vrije Universiteit Amsterdam
Oncogénétique Clinique
Assistance Publique – Hopitaux de Paris, and Université de Paris, Paris, France

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Abstract

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.

Original language	English
Pages (from-to)	pky023
Journal	JNCI cancer spectrum
Volume	2
Issue number	2
DOIs	https://doi.org/10.1093/jncics/pky023
Publication status	Published - Apr 2018

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SDG 3 Good Health and Well-being

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@article{91a8236063544976a313a244875ce33d,

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

abstract = "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.",

author = "\{EMBRACE, GENEPSO, BCFR, HEBON, kConFab, and IBCCS\} and Schrijver, \{Lieske H\} and H{\aa}kan Olsson and Kelly-Anne Phillips and Terry, \{Mary Beth\} and Goldgar, \{David E\} and Karin Kast and Christoph Engel and Mooij, \{Thea M\} and Julian Adlard and Daniel Barrowdale and Rosemarie Davidson and Ros Eeles and Steve Ellis and Evans, \{D Gareth\} and Debra Frost and Louise Izatt and Porteous, \{Mary E\} and Side, \{Lucy E\} and Lisa Walker and Pascaline Berthet and Val{\'e}rie Bonadona and Dominique Leroux and Emmanuelle Mouret-Fourme and Laurence Venat-Bouvet and Buys, \{Saundra S\} and Southey, \{Melissa C\} and John, \{Esther M\} and Chung, \{Wendy K\} and Daly, \{Mary B\} and Anita Bane and \{van Asperen\}, \{Christi J\} and \{G{\'o}mez Garcia\}, \{Encarna B\} and Mourits, \{Marian J E\} and \{van Os\}, \{Theo A M\} and Marie-Jos{\'e} Roos-Blom and Friedlander, \{Michael L\} and Sue-Anne McLachlan and Singer, \{Christian F\} and Tan, \{Yen Y\} and Lenka Foretova and Marie Navratilova and Anne-Marie Gerdes and Trinidad Caldes and Jacques Simard and Edith Olah and Anna Jakubowska and Brita Arver and Ana Osorio and Catherine Nogu{\`e}s and Nadine Andrieu",

note = "Erratum to {"}Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study{"} by Lieske H Schrijver et al [This corrects the article DOI: 10.1093/jncics/pky023.][This corrects the article DOI: 10.1093/jncics/pky023.].",

year = "2018",

month = apr,

doi = "10.1093/jncics/pky023",

language = "English",

volume = "2",

pages = "pky023",

journal = "JNCI cancer spectrum",

issn = "2515-5091",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Oral Contraceptive Use and Breast Cancer Risk

T2 - Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

AU - EMBRACE, GENEPSO, BCFR, HEBON, kConFab, and IBCCS

AU - Schrijver, Lieske H

AU - Olsson, Håkan

AU - Phillips, Kelly-Anne

AU - Terry, Mary Beth

AU - Goldgar, David E

AU - Kast, Karin

AU - Engel, Christoph

AU - Mooij, Thea M

AU - Adlard, Julian

AU - Barrowdale, Daniel

AU - Davidson, Rosemarie

AU - Eeles, Ros

AU - Ellis, Steve

AU - Evans, D Gareth

AU - Frost, Debra

AU - Izatt, Louise

AU - Porteous, Mary E

AU - Side, Lucy E

AU - Walker, Lisa

AU - Berthet, Pascaline

AU - Bonadona, Valérie

AU - Leroux, Dominique

AU - Mouret-Fourme, Emmanuelle

AU - Venat-Bouvet, Laurence

AU - Buys, Saundra S

AU - Southey, Melissa C

AU - John, Esther M

AU - Chung, Wendy K

AU - Daly, Mary B

AU - Bane, Anita

AU - van Asperen, Christi J

AU - Gómez Garcia, Encarna B

AU - Mourits, Marian J E

AU - van Os, Theo A M

AU - Roos-Blom, Marie-José

AU - Friedlander, Michael L

AU - McLachlan, Sue-Anne

AU - Singer, Christian F

AU - Tan, Yen Y

AU - Foretova, Lenka

AU - Navratilova, Marie

AU - Gerdes, Anne-Marie

AU - Caldes, Trinidad

AU - Simard, Jacques

AU - Olah, Edith

AU - Jakubowska, Anna

AU - Arver, Brita

AU - Osorio, Ana

AU - Noguès, Catherine

AU - Andrieu, Nadine

N1 - Erratum to "Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study" by Lieske H Schrijver et al [This corrects the article DOI: 10.1093/jncics/pky023.][This corrects the article DOI: 10.1093/jncics/pky023.].

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

U2 - 10.1093/jncics/pky023

DO - 10.1093/jncics/pky023

M3 - Article

SN - 2515-5091

VL - 2

SP - pky023

JO - JNCI cancer spectrum

JF - JNCI cancer spectrum

IS - 2

ER -

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

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