Preclinical Evidence for Mifepristone in Breast Cancer: A Systematic Review and Meta-analysis of Animal Studies.

Abstract

Mifepristone (MIF), an antagonist of the progesterone receptor (PR) and glucocorticoid receptor (GR), has shown antitumor activity in experimental breast cancer, but the consistency and certainty of the preclinical evidence remain unclear. We systematically searched PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure through May 5, 2026, for animal studies evaluating MIF alone or in combination with other anticancer treatments. Random-effects meta-analyses were performed using Hedges' g with restricted maximum likelihood estimation and the Knapp-Hartung adjustment. Seventeen studies contributed to the quantitative synthesis. MIF monotherapy was associated with lower tumor volume (Hedges' g = -2.77, 95% confidence interval [CI] -4.07 to -1.47) and tumor weight (Hedges' g = -2.52, 95% CI -4.74 to -0.29), whereas the overall tumor-area estimate was inconclusive (Hedges' g = -0.80, 95% CI -1.77 to 0.16). MIF-containing combination regimens were associated with lower tumor volume than the corresponding MIF-free backbone regimens (Hedges' g = -1.28, 95% CI -1.94 to -0.63). No statistically significant difference in terminal body weight was observed under either treatment framework. Exploratory subgroup analysis identified an interaction between PR isoform context and the tumor-area effect estimate (P for interaction = 0.0004), whereas no evidence of an interaction was observed between the broader breast-cancer biological contexts for tumor volume (P for interaction = 0.769). Heterogeneity was substantial for several outcomes, and the certainty of evidence was low to very low. The available animal evidence supports further investigation of MIF in biologically characterized breast cancer models, but does not establish clinical efficacy, validated predictors of treatment response, or overall treatment safety. PROSPERO: CRD420261386224.