Stefanovic, Stefan (55389549800)Stefan (55389549800)StefanovicWirtz, Ralph (23098919300)Ralph (23098919300)WirtzSütterlin, Marc (7004657756)Marc (7004657756)SütterlinKaric, Uros (57201195591)Uros (57201195591)KaricSchneeweiss, Andreas (55113126600)Andreas (55113126600)SchneeweissDeutsch, Thomas M. (57191361152)Thomas M. (57191361152)DeutschWallwiener, Markus (14626847500)Markus (14626847500)Wallwiener2025-07-022025-07-022023https://doi.org/10.21873/anticanres.16293https://www.scopus.com/inward/record.uri?eid=2-s2.0-85150962212&doi=10.21873%2fanticanres.16293&partnerID=40&md5=e619ffae4b8e181cc07e5ad1d05d7798https://remedy.med.bg.ac.rs/handle/123456789/11903Background/Aim: Loss of differentiation of breast cancer cells in association with a down-regulated class I human leukocyte antigen (HLA) expression can lead to proliferation unhampered by cytotoxic T lymphocytes, which has been proven to be of prognostic relevance. The objective of this study was to determine the levels of HLA-A and HLA-B/C expression in metastatic breast cancer (MBC) cells and their usefulness for predicting 5-year survival. Materials and Methods: This prospective double-blinded cohort study analyzed patients starting a new line of therapy for MBC. RT-qPCR was used to determine the levels of HLA-A and B/C expression in MBC cells and the mRNA-based tumor intrinsic subtype. Two receiver operating characteristic curves (ROC) were constructed in order to determine whether HLA-A and HLA-B/C expression levels can be used for predicting 5-year survival. Youden J points, and sensitivity and specificity optimized cut-off points were determined for both ROC curves. Results: We enrolled 34 patients. The ROC curve for HLA-B/C had the highest AUC compared to HLA-A (0.55 vs. 0.42). High levels of HLA-A and HLA-B/C expression (40-ΔΔCT of 33.5 and 31.9, respectively) were highly specific (reaching 87.5% for HLA-A and even 100% specificity for HLA-B/C) yet insensitive for five-year survival in our study. Conclusion: High expression of certain class I HLA molecule subtypes by MBCs, in particular high HLA-A or B/C expression by MBC cells seems very specific in predicting the 5-year survival. We determined cut-off values for these HLA molecule clusters with high specificity, which might help identify patients with a favorable prognosis as prognosticators of a 5-year overall survival if their sensitivity is improved in larger prospective cohorts. © 2023 International Institute of Anticancer Research. All rights reserved.Breast cancercut-offHLA-AHLA-B/Cprognosticator