Abstract PS4-07-18: Association of tumor-infiltrating lymphocytes (TILs) with outcomes in patients with early TNBC treated with neoadjuvant chemotherapy with or without pembrolizumab

Abstract Introduction: Neoadjuvant chemotherapy (CT) with pembrolizumab (P) is standard for most patients (pts) with high-risk early TNBC. Biomarkers for the addition of P to CT are lacking. The prognostic and predictive value of TILs in pts who receive neoadjuvant CT+P vs CT alone and the significance of change in TILs from pre- to post-treatment samples remains unclear. Methods: From the prospective DFCI Multicenter TNBC Registry, pts with stage I-III TNBC who received neoadjuvant CT or CT+P were identified. Stromal TILs were scored in tumor samples at baseline (BL) and surgery (if residual disease, RD). TILs were evaluated as a continuous and binary variable using a threshold selected based on BL distribution. Fisher’s exact test was used to compare TILs between CT and CT+P, and between RCB groups. Association with pathologic complete response (pCR) and with recurrence-free (RFS), distant recurrence-free (DRFS) and overall survival (OS) were evaluated using logistic regression and Cox proportional hazards models, respectively, adjusting for clinical stage and neoadjuvant treatment. All statistical tests were two-sided (significance p 0.05). Results: Between 5/2019-1/2024, 121 TNBC pts were identified; 18 (14.9%) stage I, 49 (40.5%) stage II, 52 (43.0%) stage III, 2 (1.7%) unknown. 19 (15.7%) had germline BRCA1/2 mutations. 49 (40.5%) received CT and 72 (59.5%) CT+P, with anthracycline-based CT in 40 (81.6%) and 62 (86.1%) pts, respectively. The pCR rate was 51.0% (25/49; 95% CI 36.3-65.6%) with CT alone and 58.3% (42/72; 95% CI 46.1-69.8%) with CT+P. Median follow-up was 2.2 years (interquartile range IQR 1.4-3.9): CT, 4.2 years (IQR 3.4-5.1); CT+P, 1.7 years (IQR 1.2-2.2). 115 pts had TILs scored at BL and 41 at RD, of whom 35 had paired samples. BL TILs (range 0-90%) were categorized by quartiles (5%, 10%, 30%) with 10% used for primary analysis. Both BL and RD TILs did not differ between CT vs CT+P as a continuous variable (BL p=0.11; RD p=0.56) or ≥10% cutoff (BL p=0.62; RD p=0.56). High BL TILs (≥ 10%) were significantly associated with pCR and this did not differ by treatment (interaction p=0.36). No association was observed between TILs (at BL or RD) and RCB class (TILs as continuous variable: BL p=0.36, RD p=0.84; or 10% cutoff: BL p=0.31, RD p=0.86). High BL TILs (≥ 10%) were associated with longer RFS (aHR 0.15, p=0.01), DRFS (aHR 0.17, p=0.01) and OS (aHR 0.19, p=0.05; or as a continuous variable, aHR per 5-unit increase 0.46, p=0.05). Neither TILs in RD nor increase from BL to RD (in 14/35 pts, 40%) were associated with RFS, DRFS or OS. Conclusion: In this multicenter TNBC cohort, BL TILs were reinforced as a prognostic marker for pCR, regardless of the addition of P to CT. TILs at RD and changes during neoadjuvant therapy were not prognostic. Additional follow-up for survival outcomes is ongoing. Citation Format: R. S. Lee, Q. Jin, B. Binboga Kurt, B. Koca, J. Gomez Tejeda Zanudo, A. Patel, A. Barkell, J. Baginska, O. M. Cunningham, C. E. Stever, T. S. Parker, T. Rahman, M. Luo, I. G. Martino, B. M. Drummey, S. A. Virani, K. Santos, J. Bsat, C. Snow, N. Tung, S. Lo, M. G. Faggen, N. Sinclair, N. Ahmad, M. Constantinou, S. Sinclair, J. L. Meisel, S. A. Kirschner, T. A. King, R. Salgado, E. A. Mittendorf, N. U. Lin, N. Tayob, E. P. Winer, E. C. de Bruin, S. M. Tolaney, A. Moeini, A. C. Garrido-Castro. Association of tumor-infiltrating lymphocytes (TILs) with outcomes in patients with early TNBC treated with neoadjuvant chemotherapy with or without pembrolizumab 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 PS4-07-18.