BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis

BACKGROUND: The effects of body mass index (BMI) and reproductive factors may vary among breast cancer molecular subtypes, evidence of which is lacking in East Asia. METHODS: From 2002 to 2010, 1256 breast cancer patients and 1416 healthy women were recruited. Anthropometric and reproductive factors were collected from medical charts. Breast cancer subtype was defined by ER, PR, and HER2 status. Polytomous logistic regression was used to evaluate associations between risk factors and breast cancer subtypes, with subgroup analysis by menopausal status. A meta-analysis of relevant published studies in East Asia was also performed. RESULTS: In our case-control study, late menarche was negatively associated with luminal tumor risk (P(trend) = 0.03). Higher BMI was associated with risk of both luminal and triple-negative tumors (P(trend)<0.001). Late age at first live birth was associated with a 1.41- to 2.08-fold increased risk of all subtypes, while late menopause increased risk by 2.62–5.56 times. Heterogeneity of these associations was not detected for different menopausal statuses. The meta-analysis revealed a positive dose-response relationship between BMI and risk of both luminal and ER-PR- subtypes (P(trend)<0.05). Early menarche and nulliparity increased luminal tumor risk by 1.39 and 1.26 times, respectively. Non-breastfeeding also increased the risk of all subtypes. CONCLUSIONS: For East Asian women, overweight, late menopause, and lack of breastfeeding appear to increase risk of both luminal and ER−PR− tumors. Early menarche and nulliparity mainly impacted luminal tumor risk. These associations were not impacted by menopausal status.