Prognostic and Clinicopathologic Associations of LAG-3 Expression in Triple-negative Breast Cancer

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The immune checkpoint molecule lymphocyte activation gene 3 (LAG-3) is currently being investigated as a possible target for immunotherapy in triple-negative breast cancer (TNBC), frequently as an addition to treatment with programmed cell death protein 1/programmed death ligand 1 (PD-L1) inhibition. However, expression of LAG-3, the frequency of coexpression with PD-L1, and the prognostic significance of this marker have not been studied extensively in TNBC. For this study, tissue microarrays (TMAs) were constructed from surgical specimens of 514 patients with TNBC. TMAs were stained immunohistochemically for LAG-3 and PD-L1 expression. Tumor-infiltrating lymphocytes (TILs) were evaluated on full glass slides. LAG-3 expression was significantly associated with improved overall survival and relapse-free survival. When adjusted for clinicopathologic factors, each increment of 10 LAG-3-positive intratumoral lymphocytes per TMA core was associated with improved overall survival (hazard ratio=0.93, 95% confidence interval: 0.89-0.97, P=0.002), and recurrence-free survival (hazard ratio=0.91, 95% confidence interval: 0.85-0.97, P=0.002). PD-L1 expression on immune cells and PD-L1 expression evaluated with the combined positive score and TILs were also associated with improved survival in both univariate and multivariate analyses. PD-L1 expression on tumor cells was only associated with improved survival in univariate analysis. LAG-3 expression was associated with both TILs and PD-L1 expression. Coexpression of LAG-3 and PD-L1 did not confer additional survival benefits. In conclusion, LAG-3 expression is associated with improved survival in TNBC. LAG-3 is often coexpressed with PD-L1, confirming that TNBC is likely a suitable candidate for cotreatment with LAG-3 and programmed cell death protein 1/PD-L1 inhibitors. However, coexpression does not confer additional survival benefits.

Original languageEnglish
JournalApplied Immunohistochemistry and Molecular Morphology
Volume30
Issue number1
Pages (from-to)62-71
ISSN1541-2016
DOIs
Publication statusPublished - 2022

Bibliographical note

Funding Information:
Supported by the Department of Pathology, Herlev and Gentofte Hos-pital, the A.P. Møller Foundation for the Advancement of Medical Sciences, the Dagmar Marshall Foundation, the Einar Willumsen Memorial Foundation, the Eva and Henry Frænkel Memorial Foundation, and the Jørgen Holm and Elisa f. Hansen Memorial Foundation.

    Research areas

  • biomarker, immunotherapy, LAG-3, PD-L1, triple-negative breast cancer

ID: 326630278