Abstract B145: Intersection of breast cancer, immune profiles, and ethnicity: Circulating chemokines and systemic inflammation effects in breast cancer

Abstract Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC) and is disproportionately diagnosed more frequently among African American women in the US. We previously reported that African ancestry-associated Duffy-null (Fy-) allele is strongly associated with increased frequency of TNBC. Fy-, a promoter region variant within the Duffy Antigen Receptor for Chemokines (DARC) gene plays an important role in modulating levels of circulating chemokines and systemic inflammation. To better understand Fy- status in the context of BC and systemic inflammatory profiles, we quantified a panel of circulating inflammatory markers and determined Fy- status to evaluate associations via unpaired t-tests and linear regression models. We hypothesize that Fy- associated circulating biomarker levels may represent novel BC biomarkers among women of African ancestry. Our cohort included 751 BC cases across 3 demographics, Ghanaian (wAfr), African American (AA), and European American (EA) women, and 150 AA and EA non-cancer controls. Multiplex luminex assays were conducted from participant plasma to quantify 47 circulating biomarkers (8 for case-control analysis). Fy- genotype status was determined from participant blood or saliva DNA genotyped for rs2714778. We performed unadjusted and adjusted linear models, where adjusted models included age, body mass index (BMI) and TNBC status.Our case-control analysis was limited to a subset of circulating biomarkers, where we report significant circulating biomarker associations with Fy- status and self-reported race/population group (SRR). Our overall case-control analysis revealed significant increases in CCL21 and IL-6 among BC cases, indicating these biomarkers may be disease-driven. We additionally conducted case-control analyses among AA and Fy- only, respectively. CCL21 and IL-6 were elevated among AA and Fy-, but not significant. Comparison of Fy- controls versus Fy- cases indicated increased IL-6 and decreased CCL19, respectively.We analyzed the association of 47 circulating biomarkers across our BC patient population, where we compared circulating biomarker status between AA and EA, wAfr and EA, and Fy- to Fy+. CXCL11, a known strong binder of DARC, and MIF were significantly increased among Fy- BC patients, where CCL19, CCL1 and CCL2, a known strong binder, were significantly decreased. Similar significant trends were observed for CXCL11 among AA and wAfr, and CCL19 among wAfr, indicating potential ancestry and genotype-specific regulation of chemokine expression patterns linked to DARC-binding affinity and inflammatory signaling. We additionally report significant increase of CXCL2 and CCL3, and decrease of CCL24 and CCL23 among AA and wAfr, that were not shown to be associated with Fy status. The characterization at intersection of disease, demographic background, and Fy status revealed a consistent positive relationship between strong DARC-binding, inflammatory chemokines with AA, wAfr, and Fy- patients with BC. Citation Format: Kenya Bynes, Stevens Patino, Rachel Martini, Danielle Doucette, Brian Stonaker, Jason White, Melissa Davis. Intersection of breast cancer, immune profiles, and ethnicity: Circulating chemokines and systemic inflammation effects in breast cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B145.