BACKGROUNDBreast cancer (BC) is a significant global health issue, accounting for 1 in 8 cancer diagnoses worldwide. HLA class I molecules are typically expressed on the cell surface, but cancer cells can develop mechanisms to evade recognition by CTLs, including the downregulation of HLA class I expression. In this context, we aimed to conduct a systematic review and meta-analysis to clarify the role of HLA class I expression in clinical outcomes for patients with BC.METHODSA comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases. Effect sizes, along with I2 and Tau2 statistics, were used to assess heterogeneity through a DerSimonian and Laird random-effects model. Statistical analyses were performed using R statistical software, version 4.2.3.RESULTSAmong the 8 included studies, most of the analyzed samples consisted of ductal carcinoma cases (1588, 86.39 %), from the luminal (A or B) intrinsic subtype (1865, 69.07 %), with no lymph node metastasis (2658, 57.24 %), no HER2 overexpression (2594, 67.46 %), negative Ki67 status (1721, 71.26 %), and positive hormone receptor status (4732, 64.05 %). The analysis revealed a significant reduction in disease-free survival (HR 0.57; 95 % CI 0.34 to 0.95; p = 0.034; I2 = 84 %) in the group with low HLA-I expression. However, no significant difference was found between the groups with high and low HLA-I expression regarding overall survival (HR 0.77; 95 % CI 0.28 to 2.14; p = 0.62; I2 = 86 %).CONCLUSIONSThis systematic review and meta-analysis demonstrated that HLA class I expression is associated with a significant improvement in disease-free survival, though no significant effect on overall survival was observed.