Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial

Abstract

Purpose: Tumor microenvironment (TME) immune markers tumor-infiltrating lymphocytes (TIL), and hormone receptor (HR) have been correlated with both response to neoadjuvant therapy and status for pathologic complete response (pCR), disease-free survival prognosis in patients with breast cancer. Here, immune-cell activity (DFS), and overall survival (OS) were determined. of breast cancer tumors was inferred by expression-based analysis to Results: iICA cluster correlated with TIL levels. The highest determine if it is prognostic and/or predictive of response to pCR rates were observed in hot cluster tumors, and those with neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial relatively higher TILs. Greater inferred activity of several T-cell (NCT01583426). types was significantly associated with pCR and survival. DFS Experimental Design: Pre-study biopsies from 279 patients with and OS were prolonged in patients with hot or warm cluster HER2-negative breast cancer in the G7 trial underwent RNA-seq-tumors, the latter particularly for HR negative tumors, even if based profiling of 104 immune-cell-specific genes to assess inferred TILs were relatively low. Immune Cell Activity (iICA) of 23 immune-cell types. Hierarchical Conclusions: Overall, TIL level better predicted pCR, but iICA clustering was used to classify tumors as iICA “hot,” “warm,” or cluster better predicted survival. Differences in associations between “cold” by comparison of iICA in the G7 cohort relative to that of TILs, cluster, pCR, and survival were observed for HR-positive 1,467 samples from a tumor database established by Nantomics tumors versus HR-negative tumors, suggesting expanded study of LLC. Correlations between iICA cluster, pathology-assessed the implication of these findings is warranted.