Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Prognostic Impact of LAG-3 Expression in Early Breast Cancer

Anne-Sophie Heimes
,
Katrin Almstedt
,
Slavomir Krajnak
,
Anne Runkel
,
Annika Droste
,
Roxana Schwab
ORCID logo ,
Kathrin Stewen
,
Antje Lebrecht
,
Marco J. Battista
,
Walburgis Brenner
,
Annette Hasenburg
,
Mathias Gehrmann
,
Jan G. Hengstler
,
Marcus Schmidt
* ORCID logo
Version 1 : Received: 1 September 2022 / Approved: 6 September 2022 / Online: 6 September 2022 (03:50:19 CEST)

A peer-reviewed article of this Preprint also exists.

Heimes, A.-S.; Almstedt, K.; Krajnak, S.; Runkel, A.; Droste, A.; Schwab, R.; Stewen, K.; Lebrecht, A.; Battista, M.J.; Brenner, W.; Hasenburg, A.; Gehrmann, M.; Hengstler, J.G.; Schmidt, M. Prognostic Impact of LAG-3 mRNA Expression in Early Breast Cancer. Biomedicines 2022, 10, 2656. Heimes, A.-S.; Almstedt, K.; Krajnak, S.; Runkel, A.; Droste, A.; Schwab, R.; Stewen, K.; Lebrecht, A.; Battista, M.J.; Brenner, W.; Hasenburg, A.; Gehrmann, M.; Hengstler, J.G.; Schmidt, M. Prognostic Impact of LAG-3 mRNA Expression in Early Breast Cancer. Biomedicines 2022, 10, 2656.

Abstract

Background: Monoclonal antibodies against PD-1 or PD-L1 are 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 ex-pression 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 ICPs and CD8 expression. Methods: Using microarray-based gene expression analysis, we examined the prognostic signif-icance for metastasis-free survival (MFS) of LAG-3 mRNA expression in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed us-ing Spearman-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 higher LAG-3 expression was associated with 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 multivariate Cox regression analysis adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and the 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 ( = 0.571; p < 0.001). Conclusion: 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.

Keywords

LAG-3; immuncheckpoints; immunotherapy; breast cancer

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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