Abstract
BACKGROUND: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. METHODS: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. RESULTS: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to understand the role of the tumor microenvironment (TME) in response to treatment. APOD, GPR132, FGF10, and HBB emerged as independent predictors of NAC response, with APOD showing a protective effect in LuminalB/HER2- patients. These results were corroborated by immunohistochemistry and public databases. Drug sensitivity analysis revealed varied responses to potential therapeutics among the non-responders. CONCLUSIONS: This study underscores the need to identify specific gene expression profiles and immune cell population changes to predict NAC responses, paving the way for personalized and effective treatments for the Colombian BC population.