Abstract C023: Overcoming chemotherapy resistance in colombian breast cancer women: Studying gene expression, genetic ancestry, and survival impact on breast cancer response to neoadjuvant treatment response
Authors: Guevara-Nieto Hedda Michelle , Alberto Orozco-Castaño Carlos Alberto , Parra-Medina Rafael Santiago , Zabaleta Jovanny , Lopez-Kleine Liliana , Combita Alba Lucia 
Published: September 2024

Abstract
Breast cancer (BC) presents significant public health challenges, especially concerning the efficacy of Neoadjuvant Chemotherapy (NAC) in advanced cases with low response rates. By exploring the tumor microenvironment (TME) and considering European and Indigenous American (IA) Ancestry in BC, we aim to predict NAC effectiveness. Our study focuses on identifying gene expression patterns, TME characteristics, genetic ancestry, and survival factors linked to NAC non-response in Colombian women with invasive BC. A transcriptomic study analyzed 58 baseline samples from women with advanced breast cancer at the Colombian National Cancer Institute, categorizing them into 29 NAC responders and 29 non-responders. The study involved analyzing differential gene expression between response groups, conducting pathway enrichment analysis, TME estimation, genetic ancestry evaluation, and performing survival analyses in a cohort of female patients who were candidates for NAC at the Colombian National Cancer Institute. Distinct gene expression profiles and pathways were observed between responders and non-responders, emphasizing Cytokine-cytokine receptor interaction, JAK-STAT, NF-kappa B, IL-17 and chemokine signaling pathways, extracellular matrix-receptor interaction, nitrogen, cysteine and methionine metabolisms. Responders showed increased B cell populations, CD4+ and CD8+ effector memory T-cells in lymphoid groups, while non-responders displayed elevated levels of CD8+ naive T-cells. Additionally, responders revealed upregulated myeloid cell populations like macrophages and dendritic cells. Samples show a genetic ancestry distribution 8% for African American, 29% indigenous American and 51% European. Longer survival rates were found in patients with higher fraction of IA ancestry (p=0.0026), while no association was found with European ancestry (p=0.14). These results were contrasted to other studies in other Latin American cohorts. The expression of immune-related genes and the composition of various immune cell subtypes within the TME are associated with responses to NAC, with significant changes observed in cell fractions regarding response type. These findings highlight potential meta-signatures that merit further exploration, including comparative assessments between immunohistochemistry (IHC) and gene expression profiling, as well as rigorous validation to guide patient selection for NAC and tailor personalized interventions. Accurate detection and evaluation of TME components play a crucial role in predicting NAC efficacy and preventing disease recurrence. Importantly, these results underscore the necessity of studying diverse populations to uncover novel insights and mitigate disparities.
Citation Format: Hedda Michelle Guevara-Nieto, Carlos Alberto Alberto Orozco-Castaño, Rafael Santiago Parra-Medina, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita. Overcoming chemotherapy resistance in colombian breast cancer women: Studying gene expression, genetic ancestry, and survival impact on breast cancer response to neoadjuvant treatment response [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C023.