Abstract PS4-12-05: Real-world evidence of ethnic-racial disparities in tumor-infiltrating lymphocytes and survival outcomes in early-stage triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC), comprising 10-15% of all breast cancer cases, is characterized by an aggressive course and high early recurrence rates. Neoadjuvant chemotherapy (NACT), with the recent addition of pembrolizumab, stands as the standard treatment for early-stage TNBC, where achieving a pathologic complete response (pCR) is a strong predictor of favorable long-term survival. Ethnicity is considered a crucial factor in TNBC prognosis; notably, African American women experience higher breast cancer mortality compared to their White counterparts. This disparity may partially result from differences in the tumor microenvironment (TME). Increasing evidence points to the TME's key role, mainly the composition and density of tumor-infiltrating lymphocytes (TILs), in determining TNBC outcomes. However, the impact of racial and ethnic disparities on the prevalence of TILs and their prognostic significance remains inadequately explored. Understanding these factors could be pivotal in understanding disparities and tailoring more effective, equitable treatment strategies. Methods: The internal database of the Brazilian National Cancer Institute was queried to identify women diagnosed with TNBC who underwent NACT followed by curative surgery between January 2010 and December 2014. Patients were assigned to White or Black/Mixed-race groups for comparison. Core biopsy specimens were analyzed by immunohistochemistry (IHC) for CD4, CD8, FOXP3, and PD-L1 CPS. Complete blood counts were assessed to evaluate the pre-NACT neutrophil-to-lymphocyte ratio in peripheral blood. The correlation between racial groups and the TME composition by TILs subpopulations was evaluated. Progression-free survival (PFS) and overall survival (OS) estimates for each racial group were determined using the Kaplan-Meier method. Results: A total of 169 patients were included: 78 (46.2%) White and 91 (53.8%) Black/Mixed-race women. Clinical characteristics showed no significant differences: mean age was 50.9 (SD 11.3) vs. 50.0 (SD 10.2) years (p=0.555); mean BMI was 28.1 (SD 5.2) vs. 29.0 (SD 6.4) (p=0.351). Tumor stage II was present in 12 (15.4%) White and 16 (17.6%) Black/Mixed patients (p=0.861); tumor grade 3 in 50 (64.1%) vs. 63 (69.2%) (p=0.653). High CD4 expression was observed in 66 (88.0%) White and 70 (83.3%) Black/Mixed patients (p=0.542); high CD8 in 40 (53.3%) vs. 45 (49.4%) (p=0.738). FOXP3 high expression occurred in 38 (50.7%) vs. 35 (41.7%) (p=0.328). PD-L1 CPS ≥1% was present in 32 (41.0%) White and 37 (41.1%) Black/mixed patients (p=1.000). The CD4/FOXP3 high ratio was observed in 37 (49.3%) vs. 47 (56.0%) (p=0.499); CD8/FOXP3 high in 64 (85.3%) vs. 79 (86.7%) (p=0.979). The CD4/CD8 high ratio was more frequent in Black/Mixed (13; 15.7%) vs. White (4; 5.3%) (p=0.066). Neutrophil-to-lymphocyte ratio was similar in both groups. With a median follow-up of 62.5 months, the 5-year event-free survival (EFS) was 53.9% vs. 47.3% (p=0.45), and the 5-year overall survival (OS) was 56.1% vs. 58.6% (p=0.78) in White and Black/Mixed groups, respectively. Conclusions: These findings indicate clinical and pathological similarities between White and Black/Mixed-race women with TNBC undergoing NACT. The prevalence of TILs subtypes and PD-L1 expression showed no significant racial differences, and survival outcomes were comparable between the groups. These results suggest that differences in the TME across races are unlikely to explain racial outcome disparities. Citation Format: J. da Silva, L. de Albuquerque, F. Rodrigues, G. de Mesquita, P. Fernandes, L. da Silva, L. Thuler, A. de Melo. Real-world evidence of ethnic-racial disparities in tumor-infiltrating lymphocytes and survival outcomes in early-stage triple-negative breast cancer 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 PS4-12-05.