Abstract PS4-07-10: The Relationship Between Tumor-Infiltrating Lymphocytes (TILs), Pathologic Complete Response, and Event-Free Survival in Patients with Early-Stage Triple-Negative Breast Cancer Treated with KEYNOTE-522 regimen in a Real-World Scenario

Abstract Background: Tumor-infiltrating lymphocytes (TILs) are established prognostic and predictive biomarkers in early-stage triple-negative breast cancer (eTNBC). The addition of pembrolizumab to neoadjuvant chemotherapy (NAC) has demonstrated improved outcomes in this setting (KEYNOTE-522 trial). The role of TIL levels in this context needs to be further explored. Methods: The Neo-Real / GBECAM-0123 study is a retrospective multicenter cohort including patients (pts) with stage II-III TNBC treated with pembrolizumab plus NAC across institutions in Brazil and Argentina since 2020. Baseline stromal TILs were assessed on pre-treatment biopsies according to international guidelines and categorized as 30%, 30-49%, or ≥50%. Associations with pCR and event-free survival (EFS) were evaluated using logistic and Cox regression models, respectively. Results: A total of 248 pts were included (median age: 44 years; 70.8% with stage II disease). TILs 30%, 30-50%, and ≥50% were observed in 72.6%, 12.9%, and 14.5% of pts, respectively. In multivariable logistic regression including TILs, Ki-67 index, clinical stage, tumor grade, and number of neoadjuvant pembrolizumab cycles, both TILs ≥50% (OR 6.96, 95% CI 1.88-25.65, P=0.004) and Ki-67 ≥50% (OR 4.88, 95% CI 2.31-10.32, P0.001) were strongly associated with pCR. Nearly all pts with both high TILs and high Ki-67 achieved pCR (Table). With a median follow-up of 24 months, pts with pCR had significantly higher 2-year EFS compared to those with residual disease (95.9% vs. 76.5%, P0.001). In the multivariable Cox model, pCR and clinical stage remained independent predictors of EFS, whereas TILs were not. Pts who achieved pCR had an 80% lower risk of recurrence or death compared to those with residual disease (HR 0.20, 95% CI 0.07-0.54, P=0.002). Conversely, pts with stage III disease had significantly worse EFS compared to those with stage II (HR 3.68, 95% CI 1.58-8.53, P=0.002).Among pts with pCR, 2-year EFS was 97.0% in TILs 30%, 95.2% in TILs 30-50% (HR 1.26, 95% CI 0.12-12.42, P=0.839), and 93.2% in TILs ≥50% (HR 1.74, 95% CI 0.28-10.53, P=0.544). Among those with residual disease, 2-year EFS was 73.3% in TILs 30%, 90% in TILs 30-50% (HR 0.33, 95% CI 0.04-2.51, P=0.288), and 100% in TILs ≥50% (HR 1.39e-15, 95% CI NA, P=1.000; analysis limited by small number of pts in this group of TILs ≥50% with residual disease). Conclusion: In this real-world cohort of pts with eTNBC treated with the KEYNOTE-522 regimen, high baseline TILs and Ki-67 index were strongly associated with higher pCR rates. These findings support the role of TILs as a relevant biomarker for treatment response. Long-term outcomes were primarily driven by pathologic response and disease stage, underscoring the importance of achieving pCR. Citation Format: R. C. Bonadio, M. C. Tavares, F. C. Balint, G. Ferreira, C. dos Anjos, D. Gagliato, M. L. de Brito, D. Assad-Suzuki, D. D. Rosa, N. J. Gomes, N. C. Nunes, L. Testa, M. Rigesti, V. Baro, I. M. de Sousa, M. O. Andrade, M. Gouveia, F. Madasi, J. Bines, R. P. Ferreira, C. L. Santos, M. Tavares, M. Monteiro, Z. S. de Souza, A. U. Gomes, B. M. Zucchetti, A. Ferrari, M. F. Monteiro, P. A. Signorini, A. Aguilar, S. Sanches, P. G. Hoff, M. Estevez-Diz, R. Barroso-Sousa. The Relationship Between Tumor-Infiltrating Lymphocytes (TILs), Pathologic Complete Response, and Event-Free Survival in Patients with Early-Stage Triple-Negative Breast Cancer Treated with KEYNOTE-522 regimen in a Real-World Scenario 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 PS4-07-10.