Reproductive factors, tumor estrogen receptor status and contralateral breast cancer risk: results from the WECARE study

Several reproductive factors are known to be associated with risk of breast cancer; however, relationships between these factors with risk of second primary asynchronous contralateral breast cancer (CBC) have not been widely studied. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) Study is a population-based case-control study of 1521 CBC cases and 2212 individually matched controls with unilateral breast cancer. Using multivariable conditional logistic regression models, we examined associations between reproductive factors and CBC risk, and whether associations differed by estrogen receptor (ER) status and menopausal status of the first breast cancer. Older age at menarche was inversely associated with CBC risk (>= 14 vs. <= 11 years risk ratio (RR) = 0.82, 95 % confidence interval (CI) 0.65-1.03, P-trend = 0.02). Among parous women, an increasing number of full-term pregnancies (FTP) was inversely associated with risk (>= 4 vs. 1 FTP RR = 0.60, 95 % CI 0.41-0.88, P-trend = 0.005). Ever breast-feeding was inversely associated with CBC risk only among women with ER-negative first tumors (ever vs. never breast-fed RR = 0.69, 95 % CI 0.48-1.00, P-heterogeneity = 0.05). Older age at first FTP was inversely associated with CBC risk among women with ER-negative first tumors (>= 30 vs. <20 years old RR = 0.66, 95 % CI 0.35-1.27, P-trend = 0.03), but suggestively positively associated with risk among women with ER-positive first tumors (P-heterogeneity = 0.03). Young age at menarche and low parity, both risk factors for first primary breast cancer, were also associated with overall CBC risk. Reductions in risk associated with breast-feeding were limited to women with ER-negative first tumors, who are at higher CBC risk than women with ER-positive primaries.