Relationship between reproductive factors and risk of luminal, triple-negative, and HER2-overexpressing breast cancer by race/ethnicity

Background: Black, Hispanic, and Asian/Pacific Islander (API) women are disproportionately affected by less-common, more aggressive subtypes of breast cancer, and differences in reproductive factors may contribute to these disparities. We conducted a population-based case-case analysis comparing the risks of luminal B, triple-negative (TN), and HER2-overexpressing (H2E) breast cancer to the risk of luminal A breast cancer to better understand how reproductive risk factors influence the excess burden of aggressive breast cancer subtypes among racial/ethnic minority women. Methods: This case-case analysis was based on incident breast cancer cases, 20-69 years of age, diagnosed among residents within the respective catchment areas of two population-based cancer registries. Subtypes were defined by joint estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status: luminal A (ER+/HER2−), luminal B (ER+/HER2+), H2E (ER−/HER2+), and TN (ER−/PR−/HER2−). Data were collected through medical record reviews and structured interviewer-administered questionnaires. Categorical exposure variables included: parity, number of full-term pregnancies, history of breastfeeding, age at menopause, and age at menarche. Multinomial logistic regression models were fit to calculate odds ratios (OR) and associated 95% confidence intervals (95%CI) for each subtype relative to luminal A breast cancer, separately for non-Hispanic white, Hispanic white, Black, and Asian/Pacific Islander (API) women, and adjusting for age at diagnosis, study site, and year at diagnosis. Results: This sample included 4,557 women with breast cancer (2,047 luminal A, 335 luminal B, 1,559 TN, and 615 H2E). Among non-Hispanic white women, parity was more strongly associated with H2E than luminal A breast cancer (OR:1.24, 95%CI:0.99-1.53). Among Black and API women, parity was associated with a greater risk of TN (Black OR:1.41, 95%CI:0.72-2.78; API OR:2.43, 95%CI:1.12-5.29) and a greater risk of H2E (Black OR:2.14, 95%CI:1.78-2.57; API OR:3.73, 95%CI:2.18-6.37), relative to luminal A breast cancer. Breastfeeding was more strongly associated with the risk of luminal B than luminal A breast cancer among API women (OR:1.33, 95%CI:1.13-1.57). Older age at menarche was associated with an increased risk of TN breast cancer only among Black women. Conclusion: In this population-based study, the associations between some reproductive factors and less-common subtypes of breast cancer differed by race/ethnicity. The reproductive choices of women from different racial/ethnic groups are driven by a complex set of factors that seem to influence their subsequent risk of TN and H2E breast cancer. Future studies are needed to further clarify these mechanisms among Black and API women and to identify optimal points of intervention. Citation Format: Nicole C. Lorona, Linda S. Cook, Mei-Tzu C. Tang, Deirdre A. Hill, Charles L. Wiggins, Christopher I. Li. Relationship between reproductive factors and risk of luminal, triple-negative, and HER2-overexpressing breast cancer by race/ethnicity [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-185.