Abstract PS4-07-09: Can high TILs compensate for incomplete neoadjuvant pembrolizumab in early TNBC? Insights from the PETRHA cohort

Abstract Tumor-infiltrating lymphocytes (TILs) are an established predictive and prognostic biomarker in early triple-negative breast cancer (TNBC), associated with higher pathologic complete response (pCR) rates and favorable outcomes following chemoimmunotherapy. However, in real-world settings, access limitations, immune-related adverse events, and logistical challenges can result in early discontinuation of neoadjuvant immunotherapy. Previously, our collaborative group reported that an incomplete number of neoadjuvant pembrolizumab cycles was associated with a significantly lower pCR rate. Whether high baseline TIL levels can mitigate the impact of incomplete pembrolizumab exposure on pCR remains unknown. Patients with early TNBC who received neoadjuvant chemotherapy and pembrolizumab within the PETRHA retrospective cohort were included. Stromal TILs were assessed on pre-treatment core biopsies by local pathology teams and analyzed using two predefined cut-offs: >20% and >30%. Patients were stratified by pembrolizumab treatment completion: those who received all planned neoadjuvant cycles versus those who did not. The primary outcome was pCR rate, defined as ypT0/is ypN0. Descriptive statistics were used to summarize clinicopathological features. Associations between TILs levels, neoadjuvant pembrolizumab completion, and pCR rate were evaluated using chi-square or Fisher’s exact tests, with logistic regression used to explore associations and estimate odds ratios (OR) with 95% confidence intervals (CI). Of the 304 patients included in the PETRHA cohort, TILs data were available for 111 patients (36.5%). Among these, 59 patients (53.2%) had TILs <20% and 52 (46.8%) had TILs ≥20%, while 70 (63.1%) had TILs <30% and 41 (36.9%) had TILs >30%. Thirty-eight (34.2%) received an incomplete number of neoadjuvant pembrolizumab cycles, while 73 (65.8%) completed the regimen. Among patients who did not complete the neoadjuvant pembrolizumab cycles, those with higher TILs, whether defined as ≥20% or >30%, had significantly higher pCR rates (76.9%) compared to those with lower TILs (32.0%) (p=0.016 for both cutoffs). Similarly, among patients who completed all neoadjuvant cycles, higher TILs were again associated with increased pCR rates (>20% cut-off: 71.8% vs. 38.2%, p=0.004; and >30% cut-off: 85.7% vs. 37.8%, p<0.0001). In a multivariable logistic regression model including variables with a p-value <0.10 in univariate analysis, only TILs >30% (OR 12.74, 95% CI 2.68-60.49; p=0.001) and completion of neoadjuvant chemotherapy (OR 4.95, 95% CI 1.04-23.69; p=0.045) were independently associated with higher probability of achieving pCR. In contrast, TILs >20%, completion of neoadjuvant anthracyclines, and completion of neoadjuvant pembrolizumab were not significantly associated with pCR (p=0.633, p=0.318, and p=0.866, respectively). In our study, higher baseline TILs levels, particularly >30%, were associated with increased pCR rates, irrespective of neoadjuvant pembrolizumab completion. Notably, patients with TILs >30% who did not complete all pembrolizumab cycles had higher pCR rates than those with TILs <30% who completed the full neoadjuvant regimen (76.9% vs. 37.8%), suggesting that robust immune infiltration may partially mitigate reduced immunotherapy exposure. However, the highest pCR rate was observed in patients with both high TILs and complete neoadjuvant pembrolizumab treatment (85.7%), supporting a potential synergistic effect between host immune activation and full immunotherapy administration. Citation Format: D. Vazquez-Juarez, A. Aranda-Gutierrez, Y. Chavarri-Guerra, F. Petracci, O. Peña-Curiel, F. Acevedo, E. Zamudio Lozoya, L. Gonzalez Gonzalez, W. Mantilla, S. Franco, C. Arce Salinas, K. Centelles López, H. Gomez, P. Carreon, E. Aguirre Alvarez, A. Lopez-Galindo, B. Martinez-Cannon, M. Garcia Garces, E. Korbenfeld, A. Benitez-Cruz, E. Willars, M. Lema, C. Lema, C. Villarreal-Garza. Can high TILs compensate for incomplete neoadjuvant pembrolizumab in early TNBC? Insights from the PETRHA 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 PS4-07-09.