Correlation of HLA-A and HLA-B/C Expression With ESR1 Expression in Patients With Metastatic Breast Cancer as a Potential Prognosticator of Favorable Distant Disease-free Survival

Abstract

Background/Aim: The loss of breast cancer cell differentiation during metastatic progression leads to a down-regulation of class 1 human leukocyte antigen (HLA) expression, which in turn hinders cytotoxic T lymphocytes from effectively preventing tumor cell proliferation. Consequently, one would expect that decreased HLA expression would correlate with decreased 5-year survival. However, estrogen receptor alpha (ESR1) is known to be positively associated with overall survival. The study aimed to determine the expression levels of HLA-A, HLA-B/C, and ESR1 and to assess their influence on distant disease-free survival (DDFS). Materials and Methods: This retrospective subgroup analysis of the initial prospective, single-center, double-blind cohort study included a total of 34 patients who underwent a new treatment line for metastatic breast cancer (MBC). The MBC cells were examined using RT-qPCR. Results: The acquired data and the subsequent survival and ROC analyses indicated a positive association of reduced expression of HLA-A and HLA-B/C with DDFS. A statistically significant association of ESR1 with DDFS could not be shown. Conclusion: A potential positive association between reduced expression of HLA-A and HLA-B/C and DDFS is observed. This contrasts with the generally observed association between HLA expression loss and poor prognosis, as reported in previous protein-based studies. In metastatic settings, reduced expression of particular HLA subsets, measured at the mRNA level, might have a protective effect against disease progression. ©2025 The Author(s).