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Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy

Assessing tumor-infiltrating lymphocytes (TILs) in routine biopsies predicts response to neoadjuvant chemotherapy in breast cancer, and adding morphological features of the infiltrate improves that prediction, according to a study in 477 patients.

What was known

TILs are a recognized marker of response to neoadjuvant chemotherapy and of prognosis in breast cancer, especially in triple-negative and HER2-positive subtypes. However, it was not fully established whether the morphological features of the inflammatory infiltrate — beyond its quantity — added predictive value.

What this work adds

477 patients with stage II-III breast cancer treated with neoadjuvant chemotherapy between 2009 and 2016 were analyzed. Diagnostic biopsies were prospectively re-evaluated. TILs were quantified according to the International TILs Working Group recommendations, and morphological features of the infiltrate (cell composition, heterogeneity and localization) were assessed with standardized criteria. Pathological complete response was defined as the absence of invasive tumor in the breast and axillary lymph nodes.

Main results

A TIL cutoff above 20% was optimal for predicting complete response. High TILs were associated with higher-grade tumors, elevated Ki-67, HER2-positive and triple-negative subtypes, the presence of plasma cells, and intraepithelial and heterogeneous infiltrates. In the overall cohort, TILs above 20% significantly increased the likelihood of complete response (OR 3.9; 95% CI 2.5-6.0). Integrating the morphological features improved predictive accuracy, especially in luminal B tumors.

What it means

The authors conclude that TIL assessment on routine hematoxylin-eosin-stained biopsies is a robust predictor of response that requires no additional techniques or cost, and that integrating simple morphological features improves accuracy and could refine treatment stratification. For breast units, this reinforces the value of a careful pathology report as an accessible tool to guide decisions.

Reading from the breast unit

For breast units, this reinforces the value of a careful pathology report as an accessible tool to guide decisions, without the need for additional techniques.

Reference: Azcárate J, Petit A, Soler-Monsó T, Quirós E, Vethencourt A, Stradella A, et al. Tumor-Infiltrating Lymphocytes as Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer: Added Value of Morphological Characterization Beyond Quantification. Cancers, 2026. DOI

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