Association of body mass index and age with subsequent breast cancer risk in premenopausal women

Importance The association between increasing body-mass index (BMI) and breast cancer risk is unique in cancer epidemiology in that there is a cross-over effect, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterised but might be important in our understanding of breast cancer causation. Objective To investigate, in more detail than previously possible, the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, breast cancer risk factors and tumour characteristics. Design We pooled individual-level data from 19 prospective cohorts to estimate hazard ratios (HR) of premenopausal breast cancer in relation to BMI over the age range 18-54 years by Cox regression Setting Multicentre Participants 758,592 premenopausal women, followed up for a median 9.3 years per woman, including 13,082 incident breast cancer cases. Exposure BMI at ages 18-24, 25-34, 35-44 and 45-54 years Main Outcome Invasive or in-situ premenopausal breast cancer Results There were inverse, linear, associations of BMI with breast cancer risk which were stronger for BMI in young adulthood (HR per 5 kg/m2= 0.77, 95% confidence interval (CI): 0.73-0.80 for BMI at ages 18-24) than for BMI at older ages (e.g. HR=0.88, 95% CI: 0.86-0.91 at ages 45-54 years). The inverse associations were observed even among non-overweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI category at ages 18-24 (HR=0.24, 95% CI: 0.14-0.40 for 35.0 vs. Conclusion and Relevance Increased adiposity is associated with a reduced premenopausal breast cancer risk, at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations were observed for BMI in early adulthood, with a fourfold gradient in risk. Understanding the biological mechanisms underlying these associations could have important preventive potential.