Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil-Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer

Abstract

PURPOSE: Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. RESULTS: Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (-30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). CONCLUSION: In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.