Identification of neoadjuvant chemotherapy response transcriptomic meta-signatures in invasive breast cancer in Latino patients

Breast cancer is a highly heterogeneous disease with varying incidences and mortality rates among women from different populations worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer; however, its efficacy differs significantly among breast cancer subtypes. This study aimed to investigate the genes linked to response to NAC in Colombian women with invasive breast cancer. RNA sequencing was performed on formalin-fixed paraffin-embedded tissues from 58 patients, categorized into 29 NAC responders and 29 non-responders. Differentially expressed genes (DEGs) were identified for each molecular subtype and their prognostic performance was evaluated using risk scores. Functional enrichment analysis revealed pathways related to the immune system in the non-responders. Cytokine target activity and immune cell population changes were assessed to understand the role of the TME in the response to treatment. APOD, CCL19, GPR132, FGF10, and HBB were identified as independent predictors of NAC response, with APOD showing a protective effect in LuminalB/Her2- patients. RT-PCR and immunohistochemistry were used to validate these findings. Drug sensitivity analysis showed varying sensitivities to potential therapeutic drugs among the non-responders. This study highlights the importance of identifying specific gene expression profiles and immune cell population changes to predict NAC response in patients with breast cancer, potentially leading to personalized and effective treatment strategies for the Colombian population Overall design: After obtaining informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy were recruited for this study. Histopathological review of pre- and post-chemotherapy biopsies was performed by an expert pathologist who reviewed the slides and outlined the tumor tissue. Following completion of the neoadjuvant regimen, treatment response was evaluated using surgical specimens obtained by a pathologist. A pCR was established according to the most accepted definition: the absence of infiltrating components in the breast and lymph nodes (ypT0/is or ypN0). Patients were classified as responders if they showed pCR and non-responders if they did not present with pCR. RNA sequencing was performed on formalin-fixed paraffin-embedded pretreatment (baseline) tissues from 58 patients (29 NAC responders and 29 non-responders). Differentially expressed genes (DEGs) were identified between the responders and non-responders for each molecular subtype.