Excess body fat and adult weight gain are well-established risk factors for postmenopausal breast cancer. However, it is unclear whether the risk of breast cancer associated with adult weight gain is evident throughout the entire adulthood rather than weight gained only at specific susceptable life stages. We prospectively examined the relations of adiposity and adult weight change to the incidence of breast cancer among 99,039 postmenopausal women aged 50-71 years in the NIH-AARP Diet and Health Study, who provided complete information on anthropometric factors by self-report at baseline in 1996. During follow-up through 2000, 2,111 incident breast cancers were ascertained through linkage with state cancer registries. Cox proportional hazards regression was used to estimate relative risk (RR) and 95% confidence intervals (CI), adjusting for age, race, family history of breast cancer, education, age at menarche, age at menopause, age at first birth, parity, smoking status, physical activity, total energy intake, height, and menopausal hormone therapy (MHT). Current body mass index (BMI, kg/m2) was associated with an increased risk of breast cancer, particularly among non-current MHT users (p for interaction with MHT=0.004). Among non-current MHT users, the RRs of breast cancer according to increasing BMI categories (15-18.4, 18.5-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9, 35.0-39.9, and ≥ 40) were 0.64, 1.00 (referent), 1.19, 1.35, 1.52, 1.56, 1.91, and 2.10 (95% CI=1.46-3.03), respectively. Weight gained during early premenopausal adulthood, late premenopausal adulthood, and postmenopausal adulthood was independently associated with increased risk of breast cancer among non-MHT users. A particularly strong association was observed for weight gained during postmenopausal adulthood (RR for weight gain of 2.1-9.9 kg versus ± 2 kg=1.34 (95% CI=1.11-1.60)). The association with overall adulthood weight gain was stronger for advanced breast cancer (RR for ≥ 30 kg weight gain versus -2 to 10 kg=2.81; 95% CI=1.67-4.32) than non-advanced disease (RR=1.88; 95% CI=1.35-2.62). Also, the relation with weight gain was positive for tumors that were both estrogen receptor (ER) and progesterone receptor (PR) positive (RR=2.64; 95% CI=1.60-4.34), but suggestively inverse for ER- and PR- tumors (RR=0.42; 95% CI=0.15-1.22). No relation was found between weight gain and breast cancer risk among current MHT users. These data support the hypothesis that adiposity and adult weight gain are associated with increased risk of postmenopausal breast cancer, and suggest the importance of healthy weight maintenance throughout adulthood in the reduction of breast cancer risk.

[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]