Abstract PS4-04-01: A 15-Gene Predictive Signature for Pathologic Complete Response in Triple-Negative Breast Cancer: Validation Across Institutional and TCGA Cohorts

Abstract Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is a strong prognostic marker in triple-negative breast cancer (TNBC). However, predictive biomarkers for pCR remain limited. This study aimed to identify gene expression profiles associated with pCR in TNBC to aid treatment stratification. Methods: Tumor samples were obtained from 16 TNBC patients treated with NAC at Kaohsiung Medical University Hospital (KMUH), including 5 pCR and 11 non-pCR cases. RNA sequencing (RNA-seq) was performed, and differentially expressed genes (DEGs) were identified using DESeq2 (|log2FC| ≥ 2, adjusted p < 0.05). Expression profiles were compared with a validation cohort of 27 chemotherapy-responsive TNBC cases from The Cancer Genome Atlas (TCGA). Overlapping DEGs were identified via Venn diagram analysis. Drug-gene interaction databases were queried to assess therapeutic relevance. Results: A total of 175 DEGs were found in the KMUH cohort, with 146 upregulated and 29 downregulated in non-pCR tumors. Fifteen DEGs showed consistent expression patterns between KMUH non-pCR tumors and both KMUH pCR and TCGA responder cohorts. These genes were enriched in pCR samples and may serve as predictive biomarkers. Several candidates were identified as potentially druggable, suggesting relevance for therapeutic targeting. Conclusions: We identified a 15-gene signature associated with pCR in TNBC, validated across independent cohorts. These biomarkers may inform treatment decisions, improve patient stratification, and offer new directions for targeted therapy development in chemoresistant TNBC. Citation Format: M. Hou, M. Pan, S. MOI, F. Chen, C. Luo. A 15-Gene Predictive Signature for Pathologic Complete Response in Triple-Negative Breast Cancer: Validation Across Institutional and TCGA Cohorts [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-04-01.