Abstract 3791: Triggering receptor expressed in myeloid cells 1 (TREM1) is a predictive marker for breast cancer therapeutics

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Abstract Triggering receptor expressed on myeloid cells-1 (TREM1) is a cell surface immunoglobulin that amplifies pro-inflammatory responses in myeloid cell populations and has been implicated in carcinogen-induced liver cancer. However, its role in breast cancer is unknown. In a recent screen to identify gene expression patterns associated with breast cancer outcomes, we identified a significant and reproducible positive association between TREM1 expression and breast cancer recurrence in two large breast cancer cohorts comprising 1,984 and 616 patients (p<0.001 and p=0.003, respectively). TREM1 expression was significantly associated with recurrence in both basal-like (p<0.001) and luminal tumor subtypes (Luminal A, p=0.047; Luminal B, p=0.022) and remained significant (p<0.001) in a multivariate Cox regression model, independent of histologic grade, tumor size, nodal status, patient age, treatment and molecular subtype. In pre-treatment biopsies of patients treated with neoadjuvant chemotherapy, high TREM1 expression was associated with a significant decrease in pathologic complete response (pCR) rate (p<0.001), especially in those tumors estimated to have high levels of lymphocytic infiltrate that otherwise associated with an increased pCR rate, consistent with an immune regulatory function for TREM1. Bioinformatics analysis of genes reproducibly correlated with TREM1 expression in breast tumors revealed significant enrichment in myeloid immune cell populations (p<0.001) in general, and neutrophils (p<0.001), M0 macrophages (p<0.001) and M2 macrophages (p<0.001), in particular. Immunohistochemical analysis of breast tumor tissues confirmed colocalization of TREM1 protein expression with the pan-macrophage marker, CD68. These findings, together with the established role for TREM1 in promoting inflammation, fit a model where tumor-infiltrating TREM1-positive myeloid cells impact breast cancer outcomes by promoting immune evasion. Citation Format: Ashok K. Pullikuth, Julia Chifman, Eric D. Routh, Jeff Chou, Guangxu Jin, Michael A. Black, Lance D. Miller. Triggering receptor expressed in myeloid cells 1 (TREM1) is a predictive marker for breast cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3791.