Data from Inferred immune-cell activity is an independent predictor of HER2 negative breast cancer prognosis and response to paclitaxel-based therapy in the GeparSepto trial

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Abstract Purpose. Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in breast cancer (BC) patients. Here, immune-cell activity of BC tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426). Experimental Design. Pre-study biopsies from 279 HER2 negative BC patients in the G7 trial underwent RNAseq-based profiling of 104 immune-cell specfic genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types. Hierarchical clustering was used to classify tumors as iICA ‘hot’, ‘warm’ or ‘cold’ by comparison of iICA in the G7 cohort relative to that of 1467 samples from a tumor database established by Nantomics LLC. Correlations between iICA cluster, pathology-assessed TILs, and hormone receptor (HR) status for pathologic complete response (pCR), disease-free survival (DFS) and overall survival (OS), were determined. Results. iICA cluster correlated with TIL levels. The highest pCR rates were observed in hot cluster tumors, and those with relatively higher TILs. Greater inferred activity of several T-cell types was significantly associated with pCR and survival. DFS and OS were prolonged in patients with hot or warm cluster tumors, the latter particularly for HR negative tumors, even if TILs were relatively low. Conclusions. Overall, TIL level better predicted pCR, but iICA cluster better predicted survival. Differences in associations between TILs, cluster, pCR and survival were observed for HR positive versus negative tumors, suggesting expanded study of the implication of these findings is warranted.