Tumor-Infiltrating lymphocyte dynamics as biomarkers of neoadjuvant treatment response in luminal breast cancer.
[BACKGROUND] Tumor-infiltrating lymphocytes (TILs) are established immune biomarkers in breast cancer; however, their clinical relevance in hormone receptor–positive/HER2-negative (HR+/HER2−) disease
APA
Uguztemur E, Dogan M (2026). Tumor-Infiltrating lymphocyte dynamics as biomarkers of neoadjuvant treatment response in luminal breast cancer.. BMC cancer, 26(1). https://doi.org/10.1186/s12885-026-15795-9
MLA
Uguztemur E, et al.. "Tumor-Infiltrating lymphocyte dynamics as biomarkers of neoadjuvant treatment response in luminal breast cancer.." BMC cancer, vol. 26, no. 1, 2026.
PMID
41749117
Abstract
[BACKGROUND] 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.
[METHODS] 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.
[RESULTS] Median pre-treatment TIL was 15%, which significantly decreased to 10% after neoadjuvant chemotherapy ( = 0.003). Patients who achieved pCR had significantly higher baseline TIL levels compared with those without pCR (30% vs. 15%, = 0.027) and markedly lower post-treatment TIL levels (0% vs. 10%, < 0.001). Delta-TIL showed a strong association with pCR, with greater reductions observed in patients achieving pCR (–32.6% vs. − 3.0%, < 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.
[CONCLUSION] 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.
[METHODS] 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.
[RESULTS] Median pre-treatment TIL was 15%, which significantly decreased to 10% after neoadjuvant chemotherapy ( = 0.003). Patients who achieved pCR had significantly higher baseline TIL levels compared with those without pCR (30% vs. 15%, = 0.027) and markedly lower post-treatment TIL levels (0% vs. 10%, < 0.001). Delta-TIL showed a strong association with pCR, with greater reductions observed in patients achieving pCR (–32.6% vs. − 3.0%, < 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.
[CONCLUSION] 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.