Abstract B096: Integrative multi-level analysis of social drivers of health and tumor immunity identifies HER2+-specific disparities and subtype-specific immune remodeling in Hispanic/Latina patients with breast cancer
Abstract
Hispanic/Latinx (HL) women experience disproportionate breast cancer (BC) mortality and are more often diagnosed at younger ages with aggressive subtypes when compared to non-Hispanic White (NHW) women. While disparities likely result from the interaction of social and biologic factors, the contributions of social drivers of health (SDOH) and tumor immune biology remain understudied. We integrated patient-level SDOH with clinical outcomes, transcriptomics and immune profiling to identify factors associated with BC disparities and mechanisms underlying differential progression and survival. Transcriptomic and clinical data from the Caris Life Sciences real-world clinico-genomic (n≈11,650) and USC-ORIEN (n≈250) databases were analyzed to assess molecular pathways, immune composition (quanTIseq), and progression-free survival (PFS). Prospectively, patients treated at Los Angeles General Medical Center (LAG) or Norris Comprehensive Cancer Center completed IRB-approved, validated SDOH surveys (n=68) assessing socioeconomic status, health literacy, and related factors. A subset underwent peripheral blood immune profiling by spectral flow cytometry (n=35). LAG treated a disproportionately high proportion of HL and HER2+ BC patients. Compared with patients treated at Norris, LAG patients had significantly lower educational attainment, employment rates, income, health literacy, healthcare trust, and self-efficacy. Among HER2+ patients, HL patients had shorter PFS than NHW patients (43.3 vs 66.9 months, p=0.009). No difference in PFS was observed in other subtypes. Across retrospective cohorts, HL tumors exhibited subtype-specific immune differences, including higher CD8+ T cell, Treg fractions and lower B cell fractions. HER2+ tumors from HL patients contained fewer M2 macrophages (4.10% vs. 4.75%, p<0.05); HL TNBC tumors contained more CD8+ T cells (0.70% vs. 0.50%, p<0.05). ORIEN independently validated subtype-specific immune patterns, including higher CD8+ T cell fractions in HL HR+/HER2- tumors (0.083 vs. 0.058, p<0.001). TNBC tumors in HL had higher neutrophil (0.006 vs. 0.002, p=0.01) and lower B cell fractions (0.19 vs. 0.14, p=0.007). In the prospective flow cytometry cohort, HER2+ HL patients demonstrated trends toward more circulating CD8+ T cells, PD-1+ Tregs, and G-MDSCs when compared with NHW patients. HER2+ BC was enriched in the safety-net population and associated with inferior outcomes among HL patients. Immune profiling revealed an inflamed yet immunosuppressive microenvironment, suggesting biologic vulnerability in this population. SDOH, including health literacy, healthcare trust, self-efficacy, and stress, were more strongly associated with clinical care site than race/ethnicity, highlighting the importance of healthcare access and social context in shaping BC disparities. These findings support integrating social and immune drivers into precision oncology approaches to address BC inequities. Nana A.K. Gyabaah-Kessie, Sachin K. Deshmukh, Diego I. Alvarez-Lopez, Zehui He, Seeta Rajpara, Elexa Rallos, Sabrina Carrel, Michelle Li, Batul Al-Zubeidy, Dominic Zavala, Aaron Baugh, Edgar Gonzales, Dominic Zavala, Serina Ovalle, Lori Khatchaturian, Sarai Cruz, Steven Do, Joel Sánchez Mendez, Kathy Wojcik, Daniel Flores, Ben Y. Tew, Matthew Jacobo, George W. Sledge, David Conti, Myles Cockburn, Sharon Wu, Joanne Xiu, Daphne Stewart, Anastasia Martinova, Darcy Spicer, Maryam Lustberg, Ming Li, Bodour Salhia, Robert Hsu, Mariana C. Stern, Evanthia T. Roussos Torres. Integrative multi-level analysis of social drivers of health and tumor immunity identifies HER2+-specific disparities and subtype-specific immune remodeling in Hispanic/Latina patients with breast cancer [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 B096.