Transcriptomic and functional pathway features were associated with survival after pathological complete response to...

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) has been proposed as a surrogate endpoint for the prediction of long-term survival in breast cancer (BC); however, an increased pCR rate has not clearly correlated with improved survival. We hypothesized that some transcriptomic and functional pathway features correlate with survival after pCR in BC. We utilized 2 published NAC cohorts, 105 women with gene expression data before, "Baseline", and that changed during NAC, "Delta", and TCGA database with 1068 BC patients to investigate the relationship between the efficacy of NAC and survival utilizing differentially expressed-mRNAs, construction and analysis of the mRNA-hub gene network, and functional pathway analysis. In mRNA expression profiling, S100A8 was a gene involved in survival after pCR in Baseline and NDP was a gene involved in recurrence after pCR in Delta. In functional pathway analysis, we found multiple pathways involved in survival after pCR. In mRNA-hub gene analysis, HSP90AA1, EEF1A1, APP, and HSPA4 were related to recurrence in BC patients with pCR due to NAC. TP53, EGFR, CTNNB1, ERBB2, and HSPB1 may play a significant role in survival for patients with pCR. Interestingly, high HSP90AA1, HSPA4, S100A8, and TP53, and low EEF1A1, EGFR, and CTNNB1 expressing tumors have significantly worse overall survival in TCGA BC cohort. We demonstrated the genes and functional pathway features associated with pCR and survival utilizing the bioinformatics approach to public BC cohorts. Some genes involved in recurrence after pCR due to NAC also served as prognostic factors in primary BC.