Abstract C132: Multi-omic profiling of breast cancer in Panamanian women reveals distinct genomic and transcriptomic features

Abstract

According to 2026 American Cancer Society (ACS) statistics, the incidence of breast cancer is lower for Hispanic/Latino women relative to White women (106.6 vs 139.35 per 100,000 women, respectively), and Hispanic/Latino women experience lower mortality rates (13.6 vs 19.3 per 100,000 women, respectively). These aggregated data do not account for potential heterogeneity due to country of origin. As, to our knowledge, multi-omics molecular profiling of breast cancer in Panamanian women has not been reported, the objective of this study was to analyze breast tumor tissue from Panamanian women to identify distinctive molecular signatures. We performed a retrospective analysis using de-identified FFPE blocks (n=92) and pathology reports from Panamanian breast cancer patients. We generated matched somatic mutation, copy-number, and RNAseq profiles using the Tempus xT v4 and Tempus xR platforms and compared results to genomic and transcriptomic data from non-Hispanic White (NHW) patients in the Cancer Genome Atlas (TCGA) database. While both groups showed frequent mutations in key breast cancer driver genes PIK3CA and TP53, 135 genes were more frequently mutated in Panamanian women including HLA-DRB5, HLA-DRB1, HLAB, KMT2C, NOTCH1, NOTCH3, NOTCH4, SYNE1, ZFHX3, RUNX1, POLE, and ARID1A. Interestingly, HLA class I and II loci are essentially intact in NHW tumors, but recurrently altered in tumors from Panamanian women, suggesting a population-specific antigen-presentation signature. RNAseq analysis identified 2305 differentially expressed genes, with 1825 upregulated in Panamanian and 480 in NHW. Top upregulated genes in Panamanian tumors include CTAGE8, CTAGE4, HRNR, NPIPB3, POLR2J3, POTEJ, RGPD2, RGPD8, TXNDC5 and ZBED6. Pathway enrichment analysis using GO and KEGG databases show differences in immune/antigen presentation, cell adhesion and cytoskeleton, and signaling processes. CNV losses were higher in Panamanian patients relative to NHW (180 vs 133) and included genes involved in DNA damage response and genome stability. NHW tumors were highly enriched in copy number gains (527 vs 39 in Panamanian) with the top NHW gain in MDM4. Multi-omic integration of somatic mutations, RNAseq and CNV data identified antigen processing/presentation, cell adhesion and DNA damage repair pathways as having coordinated enrichment across platforms. The PAM50 subtype classifier showed significant differences in subtype frequencies, with Panamanian enriched for basal-like (28% vs 15 %) and NHW dominated by luminal A+B (70% in NHW vs 46% in Panamanian). While this is a potential confounder, the reported molecular signals hold across subtypes in all four –omic layers and thus do not represent artifacts of subtype imbalance between cohorts. This initial multi-omics characterization provides a platform for hypothesis generation to motivate future studies that may lead to improved outcomes for Panamanian women with breast cancer. Fangfang Guo, Jorge Lasso De La Vega, Edgardo Castro-Perez, Laurie Littlepage, M. Sharon Stack, Jun Li. Multi-omic profiling of breast cancer in Panamanian women reveals distinct genomic and transcriptomic features [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C132.