Prognostic Impact of LAG-3 mRNA Expression in Early Breast Cancer

• Published in: Biomedicines Vol. 10; no. 10; p. 2656
• Main Authors: Heimes, Anne-Sophie, Almstedt, Katrin, Krajnak, Slavomir, Runkel, Anne, Droste, Annika, Schwab, Roxana, Stewen, Kathrin, Lebrecht, Antje, Battista, Marco J., Brenner, Walburgis, Hasenburg, Annette, Gehrmann, Mathias, Hengstler, Jan G., Schmidt, Marcus
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2022; MDPI
• Subjects: Analysis; Breast cancer; Cancer patients; Cancer therapies; CD223 antigen; CD8 antigen; Cell activation; Chemotherapy; CTLA-4 protein; Cytotoxicity; DNA microarrays; ErbB-2 protein; Estrogens; Gene expression; Genes; Gynecology; Health aspects; Immune checkpoint; immune checkpoints; immunotherapy; Ipilimumab; Kinases; LAG-3; Lymphocytes; Medical prognosis; Melanoma; Messenger RNA; Metastases; Monoclonal antibodies; Obstetrics; Ovarian cancer; Patients; PD-1 protein; PD-L1 protein; Pharmaceutical industry; Rankings; Therapeutic targets; Tumors; United Kingdom; Germany; United States > US; breast cancer; LAG-3; immunotherapy; immune checkpoints
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10102656

Background: Monoclonal antibodies against PD-1 or PD-L1 have been established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4), additional ICPs, such as lymphocyte activation gene-3 (LAG-3), are subject of current research. In the present retrospective gene-expression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICP and CD8 expressions. Methods: Using microarray-based gene-expression analysis, we examined the prognostic significance of LAG-3 mRNA expression for metastasis-free survival (MFS) in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed using Spearman’s rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, log-rank). In the subgroup analyses, there was a trend that a higher LAG-3 expression was associated with a favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in a multivariate Cox regression analysis, adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 (ρ = 0.571; p < 0.001). Conclusions: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints, such as LAG-3, could serve as therapeutic targets in breast cancer.