Journal
JAMA ONCOLOGY
Volume 4, Issue 11, Pages -Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaoncol.2018.1771
Keywords
-
Categories
Funding
- Breast Cancer Now
- United Kingdom National Health Service
- Institute of Cancer Research
- Avon Foundation [02-2014-080]
- US National Center for Advancing Translational Sciences [KL2-TR001109]
- Karolinska Institutet [2368/10-221]
- US National Institutes of Health (NIH) [R01CA144032, R01UM182876]
- National Institute of Environmental Health Sciences, NIH [Z01 ES044005, P30 ES000260]
- National Cancer Institute [UM1 CA176726, UM1 CA186107, UM1 CA182876, UM1 CA182934, UM1 CA164974, R01 CA058420, R01 CA092447, CA077398, CA144034]
- National Program of Cancer Registries of the Centers for Disease Control and Prevention
- US Department of Energy
- Maryland Cigarette Restitution Fund
- Cancer Council Victoria
- Australia National Health and Medical Research Council
- Breast Cancer Research Foundation [BCRF-17-138]
- Swedish Research Council
- Swedish Cancer Foundation
- Japanese Ministry of Health, Labor and Welfare
- Hellenic Health Foundation
- European Commission Health and Consumer Protection Directorate General
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer (France)
- Institut Gustave Roussy (France)
- Mutuelle Generale de l'Education Nationale (France)
- Institut National de la Sante et de la Recherche Medicale (France)
- German Cancer Aid (Germany)
- German Cancer Research Center (Germany)
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation (Greece)
- Associazione Italiana per la Ricerca sul Cancro-Italy (Italy)
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (Netherlands)
- Dutch Prevention Funds (the Netherlands)
- Dutch Zorg Onderzoek Nederland (the Netherlands)
- World Cancer Research Fund (the Netherlands)
- European Research Council (Norway) [2009-AdG 232997]
- Nordforsk (Norway)
- Nordic Centre of Excellence Program on Food, Nutrition and Health (Norway)
- Health Research Fund [PI13/00061, PI13/01162]
- Swedish Cancer Society (Sweden)
- County Council of Skane (Sweden)
- County Council of Vasterbotten (Sweden)
- Cancer Research UK [C570/A16491, C8221/A19170]
- Dahod Breast Cancer Research Program at Boston University School of Medicine
- VicHealth [209057, 396414]
- International Agency for Research on Cancer
- Netherlands Cancer Registry (the Netherlands)
- LK Research Funds (the Netherlands)
- Statistics Netherlands (the Netherlands)
- Medical Research Council (United Kingdom) [MR/M012190/1, 1000143]
- Deutsche Krebshilfe (Germany)
- Deutsches Krebsforschungszentrum (Germany)
- Regional Government of Andalucia
- Regional Government of Asturias
- Regional Government of Basque Country
- Regional Government of Murcia
- Regional Government of Navarra
- Instituto de Salud Carlos III Redes Tematicas de Investigacion Cooperativa en Salud, Spain [RD06/0020]
- [14136]
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IMPORTANCE The association between increasing body mass index (BMI; calculated as wei ght in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. OBJECTIVE To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1,1963, through December 31, 2013, and data were analyzed from September 1.2013, through December 31, 2017. EXPOSURES Body mass index at ages 18 to 24, 25 to 34,35 to 44, and 45 to 54 years. MAIN OUTCOMES AND MEASURES Invasive or in situ premenopausal breast cancer. RESULTS Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m(2) [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI >= 35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. CONCLUSIONS AND RELEVANCE The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.
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