Abstract B082: Association of CXCR6/CXCL16 axis in triple-negative breast cancer and racial disparity

Abstract

Abstract Breast cancer (BrCa) is the most common cancer in women worldwide and remains an important global health issue. The American Cancer Society recorded 252,710 new cases of BrCa in the United States in 2017, with 40,610 deaths. Though the incidence of BrCa is higher in Caucasian American (CA), African American (AA) women are often diagnosed with more aggressive TNBC at a younger age. Also, in absence of targeted therapies, cytotoxic chemotherapy remains the backbone of treatment for TNBC. But the median survival of women with advanced TNBC remains dismal. Androgen receptor (AR) has emerged as a potential target for treating TNBC; higher AR expression is a favorable prognostic factor associated with a lower clinical stage, lower histologic grade, and lower mitotic score. Several novel anti-androgenic agents alone or in combination with other agents are currently under investigation. Unfortunately, anti-AR therapies are not as beneficial in AA since AR is often low or missing in AA TNBC. Also, outcome of TNBC in AA is worse than CA, which suggests racial differences in the molecular landscape of TNBC between the two races. Hence, defining the molecular differences in TNBC between racial/ethnic groups is vital in order to effectively reduce the observed disparity in BrCa outcome. There are strong indications of a positive linkage between chemokine, cancer and metastasis. Chemokine receptor CXCR6 and its natural ligand CXCL16 are overexpressed in many cancer cells. We have shown that CXCR6 and CXCL16 axis promotes cancer by cytoskeleton rearrangement and its significance in etiopathogenesis of BrCa is well established. Goal of this study was to establish the association of CXCR6/CXCL16 axis in BrCa disparity using TCGA data and BrCa cell lines. We show overexpression of CXCR6 and CXCL16 in BrCa tissues and cell lines. Expression was higher in AA TNBC compared to CA TNBC cell lines. TCGA data confirms higher CXCR6 and CXCL16 expression in AA compared to CA BrCa and inverse association between androgen receptor (AR) and CXCR6 expression. Low AR expression was found in TNBC expressing high CXCR6 and CXCL16. In addition to this, differential phosphorylation status of signaling molecules down stream of CXCR6 in AA and CA TNBC cells was observed. In conclusion, our work highlights association of CXCR6/CXCL16 in race specific biological differences and emphasizes the potential of CXCR6/CXCL16 as a target to reduce the racial gap in TNBC outcome. Citation Format: Hina Mir, Jeronay K Thomas, Neeraj Kapur, Anita T Johnson, Shailesh Singh. Association of CXCR6/CXCL16 axis in triple-negative breast cancer and racial disparity [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B082.