Current issues in molecular biology · 2026
Dynamic Changes in PD-L1, VEGF, and TILs Following Neoadjuvant Therapy in Residual Invasive Breast Cancer.
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Bakula Marina, Rajc Jasmina, Kvolik Pavic Ana, Kvolik Slavica
Аннотация
BACKGROUND/OBJECTIVES: Neoadjuvant therapy (NAT) may remodel the breast-cancer microenvironment. We evaluated paired changes in programmed death-ligand 1 (PD-L1), vascular endothelial growth factor (VEGF), and tumor-infiltrating lymphocytes (TILs) before and after NAT, and associations with the residual cancer burden (RCB) and survival.
METHODS: This retrospective study included 102 patients with residual invasive breast cancer after NAT: 34 with luminal B-like/HER2-negative, 34 with luminal B-like/HER2-positive, and 34 with triple-negative breast cancer (TNBC). PD-L1 was assessed using the 22C3 combined positive score, VEGF by the cytoplasmic staining intensity, and stromal TILs according to international recommendations.
RESULTS: The median tumor size decreased from 2.5 to 1.7 cm (p < 0.001), the PD-L1 CPS (combined positive score) from 6 to 5 (p = 0.039), and the TILs from 15% to 10% (p < 0.001), whereas VEGF shifted toward stronger staining (p = 0.03). In TNBC, the PD-L1 CPS decreased from 10 to 5 (p = 0.003) and the TILs from 20% to 8% (p < 0.001). Biomarkers were not associated with the RCB in the overall cohort. The initial tumor size predicted RCB II/III (OR: 2.60, p = 0.038). The overall survival differed by subtype (p < 0.001).
CONCLUSIONS: NAT has induced subtype-dependent immune and angiogenic changes, supporting biomarker reassessment in residual disease.
METHODS: This retrospective study included 102 patients with residual invasive breast cancer after NAT: 34 with luminal B-like/HER2-negative, 34 with luminal B-like/HER2-positive, and 34 with triple-negative breast cancer (TNBC). PD-L1 was assessed using the 22C3 combined positive score, VEGF by the cytoplasmic staining intensity, and stromal TILs according to international recommendations.
RESULTS: The median tumor size decreased from 2.5 to 1.7 cm (p < 0.001), the PD-L1 CPS (combined positive score) from 6 to 5 (p = 0.039), and the TILs from 15% to 10% (p < 0.001), whereas VEGF shifted toward stronger staining (p = 0.03). In TNBC, the PD-L1 CPS decreased from 10 to 5 (p = 0.003) and the TILs from 20% to 8% (p < 0.001). Biomarkers were not associated with the RCB in the overall cohort. The initial tumor size predicted RCB II/III (OR: 2.60, p = 0.038). The overall survival differed by subtype (p < 0.001).
CONCLUSIONS: NAT has induced subtype-dependent immune and angiogenic changes, supporting biomarker reassessment in residual disease.