Role of tumor-infiltrating lymphocytes in early-stage triple-negative breast cancer treated with KEYNOTE-522 in real-world setting

Tumor-infiltrating lymphocytes (TILs) are established prognostic and predictive biomarkers in early-stage triple-negative breast cancer (eTNBC), yet their role in patients treated with the KEYNOTE-522 (KN522) regimen remains underexplored. The Neo-Real/GBECAM-0123 study is a real-world cohort of patients with early-stage TNBC treated with pembrolizumab plus neoadjuvant chemotherapy across Brazil and Argentina since 2020; we evaluated baseline stromal TILs (<30%, 30–49%, or ≥50%) as predictors of pathologic complete response (pCR, primary endpoint) and event-free survival (EFS, secondary endpoint). Among 248 patients, TILs were <30% in 72.6%, 30–49% in 12.9%, and ≥50% in 14.5%. pCR rose with increasing TILs: 59%, 65.6%, and 91.4% ( P = 0.001). In multivariable analysis, TILs ≥50% (OR 6.96, 95% CI 1.89–25.65, P = 0.004) and Ki-67 ≥ 50% (OR 4.89, 95% CI 2.31–10.33, P < 0.001) independently predicted pCR; virtually all patients with both TILs ≥50% and Ki-67 ≥ 50% achieved pCR ( n = 26/27, 96.3%). Among patients with pCR, 2-year EFS was uniformly high across TIL groups (97.0%, 95.2%, 93.2%; P = 0.828); among those with residual disease, EFS trended higher with increasing TILs (73.3%, 90.0%, 100%; P = 0.350), non-significant. Baseline TILs, especially with Ki-67, emerged as a strong predictor of pCR in this real-world eTNBC cohort treated with KN522, supporting their systematic assessment in future studies.