Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study

Background: Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype. Methods: Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal–lobular (n = 473)] in the Carolina Breast Cancer Study (1993–2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER−/PR−/HER2-), and HER2+ (ER−/PR−/HER2+). Results: In case–case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33–2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03–1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08–3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype. Conclusions: Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.