Background: Breast cancer (BC) mortality rates are higher among women of African descent, including Nigerian women, compared with other racial groups. In the US, BC mortality is 40% higher among African American women compared with White women, and even after accounting for socioeconomic position (SEP), comorbidities, treatment delays, and genetic background –this disparity is still not fully explained. The higher prevalence of aggressive BC subtypes in women of African descent likely plays a role, and given the shared genetic ancestry and increasing prevalence of cardio-metabolic dysregulation in both Nigerian and African American women, we sought to examine the association between measures of cardio-metabolic dysregulation (excess adiposity, dyslipidemia, CRP) on BC risk and molecular subtype among a contemporary cohort of Nigerian women. Findings might help elucidate additional risk factors for aggressive BC in women of African descent, and inform the development of effective prevention strategies in this population Approach: A total of 301 breast cancer patients recruited from four tertiary hospitals in Nigeria, and 274 healthy community controls were included in the analysis. For both cases and controls, a comprehensive questionnaire was administered, followed by physical examination by trained clinical staff and biospecimen collection. Tumor tissue samples were shipped to the US for pathological confirmation and immunohistochemistry (for cases) and for laboratory assays of cardio-metabolic biomarkers (for cases and controls). We evaluated the associations of excess adiposity, dyslipidemia (HDL and LDL cholesterol) and CRP with breast cancer risk overall and by molecular subtype (i.e. Luminal A, Luminal B, HER2+ or triple-negative/TNBC). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) after adjusting for socio-demographic and reproductive variables (age, menarche, menopause, pregnancy) Results: After adjusting for study covariates, higher BMI was associated with a 38% lower BC risk overall (aOR: 0.62; 95% CI: 0.39, 0.98), however high waist circumference was associated with a 79% increased risk of breast cancer overall (aOR: 1.79, 95% CI: 1.13, 2.82) and 2-fold increased risk of TNBC (aOR: 2.31, 95% CI: 1.00, 5.33). Lower HDL was associated with a modest, non-significantly increased risk of BC overall (aOR: 1.04, 95% CI: 0.62, 1.73), and a significant 5-fold increased risk of TNBC (aOR: 5.26, 95% CI: 1.17, 23.70). There were no significant associations observed for high LDL overall or by subtype. Separately, higher CRP (>10mg/L) was associated with over a 5-fold increased BC risk, and 77% increased risk of TNBC (OR: 1.77, 95% CI: 0.67, 4.66). Conclusion: Cardio-metabolic dysregulation, specifically high waist circumference, low HDL and high CRP appears to contribute to increased risk of aggressive TNBC subtype among Nigerian women and may be useful targets for clinical interventions

Citation Format: Tomi Akinyemiju, MEND study co-investigators. Biology of aggressive breast cancer in women of African descent [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA24.