Abstract PO5-10-03: A Translational Epidemiologic Approach to Understand Disparities in Triple Negative Breast Cancer: Integrating Germline Genomics, Genetic Ancestry, and Neighborhood Disadvantage
Authors: Goel Neha , Hernandez Alexandra , Kesmodel Susan , Kobetz Erin , Merchant Nipun , Rebbeck Timothy 
Published: May 2024

Background: Triple-negative breast cancer (TNBC) disproportionately affects women of West African ancestry and those living in neighborhood disadvantage (ND). However, these studies were limited in their ability to control for both ancestry and socioeconomic data. To overcome this limitation, we utilized the epidemiologic-genomic infrastructure of the Miami Breast Cancer Disparities (MBCD) study to evaluate the impact of ND on relative risk (RR) of TNBC, independent of West African ancestry.

Methods: A prospective cohort of 502 women with breast cancer enrolled in the MBCD study from 2020-2022. Genetic ancestry, median neighborhood-level income quartiles (ND), germline genetic mutations, and tumor characteristics were assessed. Multinomial logistic regression was used to determine the RR between West African ancestry and TNBC (compared to ER+/HER2- and HER2+ disease) after controlling for access to care measures which might impact TNBC distributions and known TNBC risk factors (e.g., age, ND, BRCA 1 mutation, obesity, screening mammography).

Results: Of the 502 women, 333 (66.33%) had ER+/HER2- disease, 67 (13.35%) had ER+/HER2+ disease, 22 (4.38%) had ER-/HER2+ disease, and 80 (15.94%) had TNBC. On univariable analysis, the highest West African quartile (RR 3.58 95%CI 1.72-7.42, p&lt; 0.001), a BRCA 1 mutation (RR 7.89 95%CI 2.25-27.64, p=0.001) were associated with a higher RR of TNBC. Conversely, decreasing ND was associated with a lower RR of TNBC (RR 0.42 95%CI 0.21-0.83, p=0.013). On covariate adjusted multivariable analysis, decreasing ND (RR 0.45 95%CI 0.22-0.99, p=0.047) and a BRCA 1 mutation (RR 12.68 95%CI 3.19-50.35, p&lt; 0.0001) were both significantly associated with TNBC compared to ER+/HER2- and HER2+ disease.

Conclusions: To our knowledge, this prospective study is the first to evaluate the combined impact of genetic ancestry, germline genomics, and social factors on RR of TNBC. We discovered that ND and BRCA 1 mutations are independent predictors of TNBC, even after accounting for known TNBC risk factors (e.g., West African ancestry). These findings suggest a potential association between ND and TNBC, thus emphasizing the importance of a translational epidemiologic approach to understand TNBC disparities that considers both genomic and non-genomic factors.

Table. Adjusted Multinomial Logistic Regression of Patient Genetic Ancestry, Sociodemographic and Tumor Characteristics Predictors of Breast Cancer Subtype

Citation Format: Neha Goel, Alexandra Hernandez, Susan Kesmodel, Erin Kobetz, Nipun Merchant, Timothy Rebbeck. A Translational Epidemiologic Approach to Understand Disparities in Triple Negative Breast Cancer: Integrating Germline Genomics, Genetic Ancestry, and Neighborhood Disadvantage [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-03.