Lymphocyte-Activation Gene-3 Expression and Prognostic Value in Neoadjuvant-Treated Triple-Negative Breast Cancer.
10.4048/jbc.2018.21.2.124
- Author:
Yunxuan WANG
1
;
Tieying DONG
;
Qijia XUAN
;
Hong ZHAO
;
Ling QIN
;
Qingyuan ZHANG
Author Information
1. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China. zqyxsci@126.com
- Publication Type:Original Article
- Keywords:
Lymphocyte-activation gene-3 protein;
Neoadjuvant therapy;
Programmed death-1;
Programmed death ligand-1;
Triple negative breast neoplasms
- MeSH:
Biomarkers;
Drug Therapy;
Humans;
Immunohistochemistry;
Lymphocytes, Tumor-Infiltrating;
Multivariate Analysis;
Neoadjuvant Therapy;
Polymerase Chain Reaction;
Prognosis;
Triple Negative Breast Neoplasms*
- From:Journal of Breast Cancer
2018;21(2):124-133
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
