Tumor-Infiltrating lymphocyte dynamics as biomarkers of neoadjuvant treatment response in luminal breast cancer

Tumor-infiltrating lymphocytes (TILs) are established immune biomarkers in breast cancer; however, their clinical relevance in hormone receptor–positive/HER2-negative (HR+/HER2−) disease remains controversial. In particular, the predictive value of TIL dynamics for pathological response and their prognostic significance for survival outcomes are not clearly defined in this subtype. This retrospective study included 87 patients with HR+/HER2 − breast cancer who received neoadjuvant chemotherapy between 2017 and 2025. Stromal TILs were assessed in pre-treatment core biopsy specimens and post-treatment surgical samples according to International TILs Working Group recommendations. Delta-TIL was calculated as the change between post-treatment and pre-treatment TIL levels. Associations between TIL parameters and pathological complete response (pCR) and progression-free survival (PFS) were analyzed using non-parametric tests, Kaplan–Meier survival analysis, and Cox regression models. Median pre-treatment TIL was 15%, which significantly decreased to 10% after neoadjuvant chemotherapy (p = 0.003). Patients who achieved pCR had significantly higher baseline TIL levels compared with those without pCR (30% vs. 15%, p = 0.027) and markedly lower post-treatment TIL levels (0% vs. 10%, p < 0.001). Delta-TIL showed a strong association with pCR, with greater reductions observed in patients achieving pCR (–32.6% vs. − 3.0%, p < 0.001). Patients who achieved pCR demonstrated significantly longer PFS compared with those without pCR. In contrast, neither baseline TIL, post-treatment TIL, nor delta-TIL independently predicted PFS. Progression risk was primarily associated with pathological tumor burden and surgical factors. Baseline TIL levels and chemotherapy-induced reductions in TILs are strongly associated with pathological response to neoadjuvant chemotherapy in HR+/HER2 − breast cancer.Although TIL dynamics may serve as a surrogate marker of treatment efficacy, they have limited value for long-term outcomes in this subtype.Larger, well-designed prospective studies are required to further clarify this relationship.