9O_PR Gene Modules and Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer. A Pooled Analysis

Abstract

ABSTRACT Purpose To identify associations between pathological complete response (pCR) and gene modules describing biologically relevant processes and “druggable” oncogenic pathways in breast cancer (BC) subtypes. Patients and methods Publicly available gene expression data from 8 studies with 996 patients treated with anthracycline ± taxane-based neoadjuvant chemotherapy were used. We computed 17 gene modules and measured odds ratios (OR) for pCR for one-unit increases in scaled modules without and with adjustment for clinicopathological characteristics. Analyses were performed in subtypes based either on estrogen receptor (ER) and HER2 status or the PAM50 classifier. The false discovery rate (FDR) was used to adjust for multiple testing. Results We observed higher pCR rates in ER-/HER2- (139 of 457, 30%) and HER2+ (52 of 144, 36%) than ER + /HER2- (42 of 395, 11%) subtype. Increased pCR was associated with high expression of immune modules in all 3 subtypes and high expression of chromosomal instability, phosphatase and tensin homolog (PTEN) loss and E2F3 modules in ER-/HER2- and ER + /HER2- but not HER2+ subtype (interactions between HER2 and each module for pCR, p Conclusions Different pathways are associated with pCR to chemotherapy in different subtypes. High expression of immune modules is independently associated with increased pCR in HER2+ and ER-/HER2- subtypes, suggesting that novel immune strategies may be tested in these subtypes. Disclosure All authors have declared no conflicts of interest.