Purpose: In this study, we aimed to evaluate lymphocyte-activation gene-3 (LAG-3) expression and its prognostic value in neoadjuvant-treated triple-negative breast cancer (TNBC).
Methods: LAG-3, programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), and CD8+ tumor-infiltrating lymphocyte (TILs) levels were examined using immunohistochemistry in 148 preand 114 post-neoadjuvant chemotherapy (NACT) specimens of human TNBC tissue. Correlations between expression levels and clinicopathological features were analyzed. Prognostic values for combined detection in TNBC following NACT were evaluated.
Results: In pre-NACT specimens, LAG-3 expression showed a significant association with pathological complete response (pCR, p=0.038) and was correlated with PD-1 (p<0.001) and PD-L1 (p=0.008). In post-NACT specimens, high expression of LAG-3 showed significant effects on nodal status (p=0.023) and PD-1 (p<0.001). The expression of immune markers on TILs significantly increased following NACT. Multivariate analysis indicated that only nodal status (odds ratio [OR], 0.226; 95% confidence interval [CI], 0.079-0.644; p=0.005) and high quantities of CD8+TILs (OR, 3.186; 95% CI, 1.314-7.721; p=0.010) are independent predictors of pCR. Nodal status (hazard ratio [HR], 2.666; 95% CI, 1.271-5.594; p=0.010), CD8+TILs (HR, 0.313; 95% CI, 0.139-0.705; p=0.005), and the LAG-3-high/PD-L1-high group (HR, 2.829; 95% CI, 1.050-7.623; p=0.040) provided prognostic values for patients with TNBC following NACT.
Conclusion: CD8+TILs were sensitive predictive markers in response to NACT. High expression of LAG-3 in residual tissues, especially in combination with PD-L1, was associated with poor prognosis.
Keywords: Lymphocyte-activation gene-3 protein; Neoadjuvant therapy; Programmed death ligand-1; Programmed death-1; Triple negative breast neoplasms.