Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer
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Purpose: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis.
Methods: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas.
Results: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (<0.001), negative lymph nodes (=0.011), early pathologic stage (=0.025), high tumor-infiltrating lymphocyte (TIL) (<0.001) counts, negative estrogen receptor (<0.001) and progesterone receptor (=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (=0.003), cytokeratin 5/6 (=0.011), epidermal growth factor receptor (<0.001), and p53 (<0.001) expression, and high Ki-67 proliferating index (<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (=0.041) and overall survival (OS) (=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284-4.445; =0.006) and overall death (HR, 3.666; 95% CI, 1.561-8.607; =0.003).
Conclusion: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.
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