Abstract
BACKGROUND: The role of body fatness in the aetiology of breast cancer is complex. We evaluated the independent and synergistic effects of body fatness, at different stages throughout a woman's life course, on premenopausal breast cancer risk. METHODS: Premenopausal participants of the Nurses' Health Study II (NHSII) were followed from 1991 up to 2009. Body fatness factors including birthweight, somatotype (a 9-level pictogram with level 1 being the leanest) at ages 5 and 10 years and body mass index (BMI) at age 18 were collected at baseline. Current BMI was updated biennially. Multivariate Cox regression models were used to evaluate the association between each body fatness factor as well as cross-classification of all factors and the incidence of breast cancer. RESULTS: Based on 1574 incident premenopausal breast cancer cases and 1 133 893 person-years of follow-up, a lower incidence was associated with lower birthweight: hazard ratio (HR) [95% confidence interval (CI)] = 0.74 (0.58-0.95) for <2.5kg vs 3.9+kg, P for trend < 0.001; higher somatotype at age 5: HR=0.57 (95% CI 0.44-0.73) for 5-9 vs 1, P fortrend < 0.0001]; and at age 10: HR=0.61 (95% CI 0.49-0.75) for 5-9 vs 1, P for trend < 0.0001]; and BMI at age 18: HR=0.67 (95% 0.47-0.95) for ≥ 27.5 kg/m(2) vs < 18.5 kg/m(2), P for trend = 0.009], after adjusting for age and body fatness measures earlier in life and other risk factors, respectively. No significant interaction between body fatness measures was found. Women with the lowest birthweight, the highest somatotype at ages 5 and 10 and the highest BMI at age 18 and currently had a 72% (95% CI 54%-83%) lower incidence of invasive premenopausal breast cancer than women with the opposite extreme of each body fatness indicator. CONCLUSION: The lowest incidence of premenopausal breast cancer was associated with the lowest birthweight and the highest childhood, adolescent and early adult body fatness.