PS2-05-16: Prognostic value of TILs variation in breast cancer undergoing neoadjuvant chemotherapy

Abstract Background/Objective: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improved event-free and overall survival, particularly in triple-negative and HER2-positive breast cancer. Tumor-infiltrating lymphocytes (TILs) are promising prognostic and predictive biomarkers, correlating with higher pCR rates in these subtypes. However, the clinical relevance of TILs variation before and after NAC remains unclear. This study aimed to investigate associations between TILs variation, pCR, Residual Cancer Burden (RCB), and pre-NAC TILs with clinical outcomes. Methods: Retrospective cohort of 302 patients treated with NAC followed by surgery at two tertiary centers in Curitiba, Brazil, from 2016 to 2020. Data were extracted from electronic medical records. Pre-NAC core biopsies and post-NAC surgical specimens were reviewed by a dedicated breast pathologist. TILs were assessed per International TILs Working Group guidelines, and analyzed as categorical variables (low ≤10%, intermediate 11-49%, high ≥50%). Post-NAC TILs were quantified in stroma adjacent to the residual tumor bed. Pathologic response was defined using the RCB classification. Statistical analysis included the Wilcoxon signed-rank and Stuart-Maxwell tests. ROC curves identified outcome-related cut-offs. Results: Of 302 patients, 30% achieved pCR (Table 1). TILs were evaluated in 183 paired samples. TILs levels significantly declined post-NAC (p<0.001), especially in pCR cases, with median decreases of 25% in RCB 0, 15% in RCB 1, and 5% in RCB 2 and 3. Post-NAC, 78% had TILs ≤10% and 8% ≥50%, versus 43% and 25% at baseline. Pre-NAC TILs >25% were associated with reduced distant recurrence risk. No significant association was found with locoregional recurrence or mortality (Table 2). Conclusion: TILs declined after NAC, particularly in pCR cases. Pre-NAC TILs >25% were linked to lower risk of distant recurrence, supporting their prognostic value in the neoadjuvant setting. Citation Format: A. A. Fornazari, I. Rabinovich, A. Sebastião, S. Boscoli, I. C. Soares, J. M. Jakobson, E. M. Kac, F. Cohene, C. de Souza, C. Urban, C. Spautz, K. F. Anselmi, F. F. Kuroda, M. T. Doria, L. P. Nissen, E. T. Schunemann, R. S. Lima. Prognostic value of TILs variation in breast cancer undergoing neoadjuvant chemotherapy [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 PS2-05-16.