Reproductive Factors and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer Among Multiethnic Women

Background: Reproductive factors are among the most well-established risk factors for breast cancer. However, their associations with different breast cancer subtypes defined by joint estrogen receptor (ER)/progesterone receptor (PR)/HER2 status remain unclear. Methods: We assessed relationships between reproductive factors and risks of luminal A (ER+/HER2−), luminal B (ER+/HER2+), triple-negative (TN; ER−/PR−/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) breast cancers in a population-based case–case study consisting of 2,710 women ages 20–69 years diagnosed between 2004 and 2012. ORs and 95% confidence intervals (CI) were estimated with luminal A cases serving as the reference group using polytomous logistic regression. Results: Earlier age at first full-term pregnancy and age at menopause were positively associated with odds of TN breast cancer (Ptrend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI, 1.08–1.89) elevated odds of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI, 1.16–2.29, Ptrend = 0.013) increased odds of this subtype compared with nulliparous women. Breast feeding for ≥36 months was associated with a 49% (OR 0.51; 95% CI, 0.27–0.99) lower odds of TN breast cancer. Conclusion: Our results suggest that reproductive factors contribute differently to risks of the major molecular subtypes of breast cancer. Impact: African American and Hispanic women have higher incidence rates of the more aggressive TN and H2E breast cancers and their younger average age at first pregnancy, higher parity, and less frequent breast feeding could in part contribute to this disparity. Cancer Epidemiol Biomarkers Prev; 25(9); 1297–304. ©2016 AACR.