Abstract 518: Association of CC chemokines with breast cancer disparity

Abstract

Abstract Despite recent advances, breast cancer (BrCa) still affects many women, and the impact is disproportional in African Americans (AA) and European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting racial difference in BrCa biology. Our laboratory was the first to show the involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner, KMplotter, and antibody microarray, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, CCL7, CCL11, CCL17, CCL20, CCL22, and CCL25 in BrCa tissues. High mRNA levels of CCL7, CCL8, CCL17, CCL20, and CCL25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, CCL7, CLC8, CCL17, CCL20, and CCL25 was highest in TNBC. The expression of CCL11 and CCL22 was associated with HER2 expression. CCL7, CCL8, CCL17, CCL20, and CCL25 were elevated in AAs. Since CCL25 showed a significant association with decreased OS in AA, we examined the expression of CCR9, which is the only receptor for CCL25, and CCR9-mediated signaling in BrCa cell lines derived from AA and EA. Our data show higher expression of CCR9 in AA than EA and distinct molecular cascade in cells derived from AA than EA. Furthermore, higher CCR9 expressing cells showed poor response to Carboplatin upon CCR9 activation. In conclusion, our data suggest the association of distinct CC-chemokines in BrCa progression, OS, and disparate disease outcome in AA compared to EA patients implying CCR9 signaling to be a potential target for improving chemotherapeutic response. Citation Format: Hina Mir, Briana A. Brock, Rajeev Samant, Shailesh Singh. Association of CC chemokines with breast cancer disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 518.