Abstract PS2-12-05: Programmed death-ligand 1expression in triple negative breast cancer: insights from an African ancestry-enriched multinational cohort

Abstract Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein expressed on tumor and immune cells that promotes immune evasion by inhibiting T-cell activation. In advanced triple-negative breast cancer (TNBC), a subtype with aggressive behavior and limited targeted treatment options, PD-L1 expression has emerged as a predictive biomarker for response to immune checkpoint inhibitors. However, most studies have focused on predominantly European-ancestry populations, leaving gaps in understanding PD-L1’s expression and clinical relevance among women of African ancestry, who are disproportionately affected by TNBC. Given TNBC’s molecular heterogeneity across ancestral groups, examining PD-L1 expression in diverse populations is critical for equitable immunotherapy and understanding ancestry-specific tumor biology.The International Center for the Study of Breast Cancer Subtypes (ICSBCS) biobank provides a unique ancestrally diverse tissue repository, enabling biomarker studies across historically underrepresented populations. Leveraging this resource, we are conducting a large-scale immunohistochemical (IHC) analysis of PD-L1 on formalin-fixed paraffin-embedded (FFPE) TNBC tissue sections. The study aims to evaluate PD-L1 in 1,000 TNBC samples, equally distributed among Ghanaian, Ethiopian, African American (AA), and European American (EA) patients. Here, we report initial findings.To date, 301 cases have been processed (AA n = 47, Ethiopian n = 12, Ghanaian n = 205, EA n = 37). PD-L1 expression, measured as percent positive tumor cells by IHC, showed means (± SD, 95% CI) of 7.25% (± 6.28, 3.34-11.16) in Ethiopian, 6.55% (± 6.28, 4.36-8.73) in EA, 5.32% (± 6.28, 3.39-7.25) in AA, and 1.13% (± 6.28, 0.20-2.06) in Ghanaian cases. Tukey-Kramer HSD comparisons revealed significant differences between Ethiopian and Ghanaian (p=0.0156), EA and Ghanaian (p<0.0001), and AA and Ghanaian (p=0.0008). Corresponding medians (IQR) were 9% (9.13%) for Ethiopian, 1% (4.5%) for EA, 2% (9.5%) for AA, and 0% (0.5%) for Ghanaian cases, reflecting heterogeneity and skewed PD-L1 expression. Initial analyses suggest differences in PD-L1 expression across self-reported race and ancestry groups. Comprehensive clinical data and additional tumor microenvironment measures, including tumor-infiltrating lymphocyte (TIL) scores, are being collected for integrative assessment of PD-L1 and its clinical significance. Continued analysis will advance understanding of population-specific tumor immunobiology and inform equitable immunotherapy approaches in TNBC.These preliminary findings underscore the value of the ICSBCS biobank in enabling ancestry-informed biomarker research in TNBC. By systematically evaluating PD-L1 across Ghanaian, Ethiopian, AA, and EA populations, this study aims to uncover differences in immune checkpoint activation to inform tailored therapies. These data are preliminary, with limitations including small sample sizes in some ancestry groups, particularly Ethiopian and EA cohorts, which may affect precision. As analysis progresses toward the full 1,000-case cohort, continued integration of clinical, pathological, and molecular data will be essential for advancing population-specific tumor immunobiology and improving equity in breast cancer outcomes. Citation Format: B. Stonaker, E. Adjei, S. Demaria, R. Martini, M. B. Davis, L. Newman. Programmed death-ligand 1expression in triple negative breast cancer: insights from an African ancestry-enriched multinational cohort [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 PS2-12-05.