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

oleh: Anne-Sophie Heimes, Katrin Almstedt, Slavomir Krajnak, Anne Runkel, Annika Droste, Roxana Schwab, Kathrin Stewen, Antje Lebrecht, Marco J. Battista, Walburgis Brenner, Annette Hasenburg, Mathias Gehrmann, Jan G. Hengstler, Marcus Schmidt

Format: Article
Diterbitkan: MDPI AG 2022-10-01

Deskripsi

<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> In the whole cohort, LAG-3 expression had no significant impact on MFS (<i>p</i> = 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 (<i>p</i> = 0.217), basal-like (<i>p</i> = 0.370) and HER2 (<i>p</i> = 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; <i>p</i> = 0.014). High LAG-3 significantly correlated with CD8 (ρ = 0.571; <i>p</i> < 0.001). <b>Conclusions:</b> 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.