J Breast Cancer.  2018 Jun;21(2):124-133. 10.4048/jbc.2018.21.2.124.

Lymphocyte-Activation Gene-3 Expression and Prognostic Value in Neoadjuvant-Treated Triple-Negative Breast Cancer

Affiliations
  • 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China. zqyxsci@126.com
  • 2Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China.
  • 3Cancer Research Institute of Heilongjiang, Harbin, China.

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.

Keyword

Lymphocyte-activation gene-3 protein; Neoadjuvant therapy; Programmed death-1; Programmed death ligand-1; Triple negative breast neoplasms
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