[December 1, 2025] In their November 2025 Nature study, Anti-progestin therapy targets hallmarks of breast cancer risk Simões et al. demonstrate that a short course of the progesterone receptor (PR) antagonist ulipristal acetate (UA) in premenopausal women with elevated inherited breast-cancer risk suppresses luminal progenitor activity, reduces epithelial proliferation, and lowers fibroglandular density. Gene set enrichment analysis of single-cell RNA-seq data using Reactome pathway annotations revealed cell-type specific responses: luminal hormone sensing (LHS) cells showed downregulation of RNA-processing pathways, whereas basal-myoepithelial cells and fibroblasts demonstrated significant upregulation of extracellular matrix (ECM)-related components. Proteomic analyses identified 65 UA-regulated proteins, and Reactome pathways mapping confirmed UA-mediated suppression of key ECM processes, including ECM proteoglycans, Collagen formation, and Integrin cell-surface interactions. Collectively, these findings highlight ECM remodeling and luminal progenitor suppression as central mechanisms through which UA may reduce breast-cancer risk.

Learn more