Tumor infiltrating lymphocytes (TILs) as a predictive marker of pathological complete response (pCR) in a diverse patient population with early triple negative breast cancer (TNBC) treated with neoadjuvant real-world KEYNOTE-522 regimen.

introductionTriple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis. Based on the KEYNOTE-522 trial, neoadjuvant pembrolizumab plus chemotherapy has become the standard of care due to significantly improved pathological complete response (pCR) rates. The presence of tumor-infiltrating lymphocytes (TILs) is a predictive biomarker of pCR. This retrospective cohort study examines a diverse patient population treated with the K522 regimen to determine if TILs predict pCR relative to other clinical and tumor-specific factors.

methodsWe retrospectively reviewed 187 patients with early-stage TNBC at two institutions (one tertiary care, one safety-net) who completed neoadjuvant K522 treatment between 2021 and 2024. Statistical analyses included Chi-squared tests, Z-tests, and univariate logistic regression to evaluate associations between TILs, ethnicity, tumor grade, and pCR, and multivariate logistic regression to assess whether the association between dose intensity and pCR differed by the presence of TILs at baseline.

resultsThe overall pCR rate was 57%; TILs were present in 52.8% of cases. TILs were associated with a significantly higher pCR rate (70% vs. 48% without TILs; p = 0.0027). While pCR rates were similar across ethnicities, Hispanic patients with TILs had significantly higher pCR than those without (80.0% vs. 51.5%; p = 0.0254). Controlling for grade, patients with TILs were 2.442 times more likely to achieve pCR (CI: 1.310-4.553; p = 0.0050). Grade 3 tumors and node-positivity with TILs also showed statistically significant rates of pCR. Logistic regression analysis revealed a significant interaction between TIL status and immunotherapy dose intensity on pCR. While dose intensity did not influence pCR in TIL-negative patients, TIL-positive patients achieved higher pCR rates with lower dose intensity (OR = 1.54, p = 0.036).

conclusionTILs serve as a strong predictive biomarker for immunotherapy response in a real-world TNBC population. Our findings regarding Hispanic, node-positive patients, and the interaction between TIL status and dose intensity suggest that TILs could guide treatment de-escalation to reduce K522-related toxicity. Standardizing TILs reporting is critical to optimizing treatment strategies and improving outcomes in underrepresented populations.