Reproductive factors and risk of contralateral breast cancer by age and hormone receptor status: The California Breast Cancer Survivorship Consortium

Associations between reproductive factors and the risk of developing a contralateral second primary invasive breast cancer (CBC) are inconclusive. A pooled cohort of women with a first primary invasive breast cancer (FBC) from five California-based studies (8045 stage I-III FBC diagnosed from 1994 to 2009) was linked with the California Cancer Registry; 532 CBC were identified. We analyzed harmonized data and evaluated associations with reproductive factors using Fine and Gray regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusted for study, age at FBC diagnosis, race and ethnicity, and other risk factors previously identified in this pooled dataset (hormone receptor status, first-degree family history of breast cancer). Associations with reproductive factors were observed only in younger FBC survivors diagnosed at age <50 years. Higher risk of CBC was associated with nulliparity (HR = 1.37, CI = 1.03-1.81) and a recent full-term pregnancy (FTP) before FBC diagnosis (<10 vs. ≥20 years: HR = 2.04, CI = 1.13-3.66). In younger survivors of hormone receptor-negative FBC, higher risk was associated with longer duration of breast-feeding (≥12 vs. <12 months: HR = 2.96, CI = 1.48-5.89). No heterogeneity in associations by race and ethnicity was observed, except for nulliparity. In older survivors, reproductive factors were not associated with the risk of CBC. Younger FBC survivors who are nulliparous or had a FTP less than 10 years before FBC diagnosis may benefit from more regular surveillance screening after FBC diagnosis.