INTRODUCTION: Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes. PATIENTS AND METHODS: An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change. RESULTS: In the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04-1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66-0.84) and BRCA2 (HR 0.76, 95% CI 0.65-0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02-1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01-1.19, respectively). CONCLUSION: Anthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.

Aix Marseille Université INSERM IRD SESSTIM Marseille France

Cancer Epidemiology Division Cancer Council Victoria Melbourne VIC Australia

Center for Hereditary Breast and Ovarian Cancer Center for Integrated Oncology Medical Faculty University Hospital Cologne Kerpener Str 62 50937 Cologne Germany

Centre Antoine Lacassagne Nice France

Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge UK

Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Cambridge UK

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia

Centre François Baclesse Caen France

Centre Léon Bérard Lyon France

Clinical Genetics Karolinska Institutet Stockholm Sweden

Clinical Genetics Service Guy's and St Thomas' NHS Foundation Trust London UK

Clinical Genetics Service Manchester Centre for Genomic Medicine Central Manchester University Hospitals NHS Foundation Trust Manchester UK

CRLCC Paul Strauss Strasbourg France

Département d'Anticipation et de Suivi Des Cancers Oncogénétique Clinique Institut Paoli Calmettes Marseille France

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA

Department of Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK

Department of Clinical Genetics Maastricht University Medical Center Maastricht The Netherlands

Department of Clinical Genetics Radboud University Medical Center Nijmegen The Netherlands

Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Genetics St George's University Hospitals NHS Foundation Trust London UK

Department of Clinical Pathology The University of Melbourne Melbourne VIC Australia

Department of Dermatology University of Utah School of Medicine Salt Lake City UT USA

Department of Epidemiology and Population Health and of Medicine Stanford University School of Medicine Stanford CA USA

Department of Epidemiology Mailman School of Public Health and the Herbert Irving Comprehensive Cancer Center Columbia University Irving Medical Center New York NY USA

Department of Epidemiology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland

Department of Genetics Division Laboratories Pharmacy and Biomedical Genetics University Medical Center Utrecht Utrecht The Netherlands

Department of Human Genetics Amsterdam UMC University of Amsterdam Amsterdam The Netherlands

Department of Medical Genetics National Institute for Health Research Cambridge Biomedical Research Centre University of Cambridge Cambridge UK

Department of Medical Oncology Peter MacCallum Cancer Centre Victoria Australia

Department of Medicine and Huntsman Cancer Institute University of Utah Health Salt Lake City UT USA

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Genetics University of Toronto Toronto ON Canada

Department of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Oncology Clinical Sciences in Lund Lund University Hospital Lund Sweden

Division of Molecular Pathology Netherlands Cancer Institute Antoni Van Leeuwenhoek Hospital Amsterdam The Netherlands

Familial Cancer Clinical Unit Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid Spain

Fred A Litwin Center for Cancer Genetics Lunenfeld Tanenbaum Research Institute of Mount Sinai Hospital Toronto ON Canada

Genomic Medicine Division of Evolution and Genomic Sciences The University of Manchester St Mary's Hospital Manchester University NHS Foundation Trust Manchester UK

Genomics Center Centre Hospitalier Universitaire de Québec Université Laval Research Center Quebec City QC Canada

Independent Laboratory of Molecular Biology and Genetic Diagnostics Pomeranian Medical University Szczecin Poland

INSERM U900 Paris France

Institut Curie Paris France

Institute for Medical Informatics Statistics and Epidemiology Leipzig University Leipzig Germany

Manchester Breast Centre Oglesby Cancer Research Centre The Christie University of Manchester Manchester UK

Mines Paris Tech Fontainebleau France

Molecular Oncology Laboratory Hospital Clínico San Carlos IdISSC Madrid Spain

MRC Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK

Oncogénétique Poitou Charentes Niort France

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton VIC Australia

PSL Research University Paris France

Sheffield Clinical Genetics Service Sheffield Children's Hospital Sheffield UK

South East of Scotland Regional Genetics Service Western General Hospital Edinburgh UK

Stanford Cancer Institute Stanford University School of Medicine Stanford CA USA

The Prevent Breast Cancer Research Unit The Nightingale Centre Manchester University NHS Foundation Trust Manchester UK

The Sir Peter MacCallum Department of Oncology University of Melbourne Parkville Australia

West Midlands Regional Genetics Service Birmingham Women's Hospital Healthcare NHS Trust Edgbaston Birmingham UK

Yorkshire Regional Genetics Service Leeds Teaching Hospitals NHS Trust Leeds UK

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