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 examine changes in breast mRNA expression following mifepristone treatment in healthy women. We analyzed 32 paired breast biopsies from 16 healthy premenopausal women at baseline and after two months of mifepristone treatment. In total, twenty-seven 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 expression gene signature was associated with breast carcinogenesis and significantly correlated 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 healthy breast tissue in vivo, enhancing the understanding of progesterone receptor antagonism and its potential protective effect against breast cancer by investigating its action in healthy breast tissue.

The authors have declared no competing interest.

NCT01931657

This study was funded by the Swedish Research Council (2012-01981, 2017-00932), the Swedish Cancer foundation (5321-9416) and the joint grant from Stockholm County Council and Karolinska Institutet (ALF)

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted at Karolinska University Hospital, Stockholm, Sweden and was approved by the Swedish Medical Products Agency (EudraCT number 2009-009014-40). The study protocol was designed according to the recommendations in the CONSORT statement and was approved by the ethical committee at Karolinska Institutet (Dnr: 2009/144-31/4) prior to recruitment. The trial was registered at clinicaltrials.gov (NCT01931657)

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The raw data and processed data files were submitted to Gene Expression Omnibus database.