The emerging role of progesterone receptor modulators in breast physiology, cancer prevention and treatment.

Progesterone is critical for cyclic breast changes and breast cancer carcinogenesis. The commercially available progesterone receptor modulators (PRMs), ulipristal acetate (UPA) and mifepristone, have been utilised for their antiprogestogen effect in gynaecology. Administration of these medicines appears to induce favourable cellular and radiographic changes in the breast. This is a narrative review of the basic science, translational and clinical trials utilising UPA and mifepristone for breast health. It integrates historical and recent trials from around the world. PRMs have shown promise in decreasing molecular markers of carcinogenesis in BRCA1 carriers. Outside of genetic cancer risk, PRMs decrease background parenchymal enhancement on breast magnetic resonance imaging and could be developed as a personalised protocol for breast cancer screening. Although there was limited efficacy of antiprogestogens in progression-free survival for people with breast cancer, there may be a role as neoadjuvant therapy prior to surgical resection. UPA and mifepristone have the potential to revolutionise breast cancer prevention, screening and treatment. As protocols emerge, gynaecologists will be on the front lines as regards both identifying patients who may benefit from these medications and serving as interdisciplinary support in accessing these medicines.