Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, 141 57 Stockholm, Sweden.
Int J Mol Sci. 2024 Jul 10;25(14):7590. doi: 10.3390/ijms25147590.
Progesterone receptor antagonism is gaining attention due to progesterone's recognized role as a major mitogen in breast tissue. Limited but promising data suggest the potential efficacy of antiprogestins in breast cancer prevention. The present study presents secondary outcomes from a randomized controlled trial and examines changes in breast mRNA expression following mifepristone treatment in healthy premenopausal women. We analyzed 32 paired breast biopsies from 16 women at baseline and after two months of mifepristone treatment. In total, 27 differentially expressed genes were identified, with enriched biological functions related to extracellular matrix remodeling. Notably, the altered gene signature induced by mifepristone in vivo was rather similar to the in vitro signature. Furthermore, this gene expression signature was linked to breast carcinogenesis and notably linked with progesterone receptor expression status in breast cancer, as validated in The Cancer Genome Atlas dataset using the R2 platform. The present study is the first to explore the breast transcriptome following mifepristone treatment in normal breast tissue in vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer.
孕激素受体拮抗作用正受到关注，因为孕激素被认为是乳腺组织中的主要有丝分裂原。有限但有前景的研究数据表明，抗孕激素在乳腺癌预防方面具有潜在的疗效。本研究报告了一项随机对照试验的次要结果，并研究了米非司酮治疗对健康绝经前妇女乳腺 mRNA 表达的影响。我们分析了 16 名女性在基线和米非司酮治疗两个月后的 32 对配对乳腺活检。共鉴定出 27 个差异表达基因，其富集的生物学功能与细胞外基质重塑有关。值得注意的是，米非司酮在体内诱导的基因特征与体外特征非常相似。此外，该基因表达特征与乳腺癌的发生有关，并且在使用 R2 平台的癌症基因组图谱数据集验证时与乳腺癌中孕激素受体表达状态显著相关。本研究首次在体内研究了正常乳腺组织中米非司酮治疗后的乳腺转录组，增强了对孕激素受体拮抗作用及其对乳腺癌潜在保护作用的理解。
