Abstract P3-05-11: Immune and basal signature correlation to targeted therapies and race in QNBC patients

Abstract

Abstract Background: African American women have worse prognosis and poor survival rates due to lack of Androgen Receptor expression. These subtypes, the Quadruple Negative Breast Cancers (QNBC), currently have no treatments. Previously, we found that AA TNBC have 28% more chance of being QNBC and have 25% higher rate of progression vs the Caucasian Americans (CA). Also, these QNBC patients have a unique immune and basal signature. Here, we explore individual genes and their correlation to race and immune therapies. Methods: We analyzed AR mRNA expression in 925 tumors from CA or AA women from The Cancer Genome Atlas and independently validated AR protein levels by immunohistochemistry in 197 primary tumors. Samples were dichotomized as AR positive or negative using mean gene expression cutoff. Gene expression comparisons among groups were determined using standard t-tests, ANOVA, and odds ratios with a significance threshold alpha of 0.05. a of 0.05. Therapy targets were selected from the list of significantly differentiated genes. Boxplots and heatmaps were made using R packages. Cumulative Incidence plots for time to progression were constructed using XLStats and Grays test for significance. Results: QNBC CA have higher expression of PDCD4 (p <.001), CD46 (p <.001), CD3EAP (p =.04) and CD84 (p =.07) compared to QNBC AA. CD47 (p = .63) and PD1 (p =.96) express no significant differences in race[CY1]. QNBC AA show higher expression of NFKB (p <.001), CCL2 (p <.001), and IL12 (p <.001) compared to QNBC CAs. Interestingly, QNBCs with high expressions of CD47 (p = .04) have poor prognosis[L2]. Thus, QNBC patients with low expression of CD46 (p =.025), PDCD4 (p < .001), and CD3EAP (p < .001) have poor prognosis and overall survival. Conclusions: Current immune targeted therapies like CD47 and PD1 looks favorable for treatment in some QNBC patients. Race appears to effect other major therapy target gene expressions in the QNBC immune basal signature as well. This may imply that QNBC AA and CA have different immune response which may explain racial progression differences. Assessment of immune markers may contribute to more accurate prognosis. Citation Format: Hughley RW, Colomb WD, Shweta T, Yates C. Immune and basal signature correlation to targeted therapies and race in QNBC patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-11.