Individualised progesterone receptor modulator prevention strategies for triple-negative breast cancer in BRCA1 pathogenic variant carriers

Women with germline BRCA1 pathogenic variants face a very high risk of early-onset triple-negative breast cancer (TNBC), with risk-reducing mastectomy currently the only established preventive option. Emerging evidence suggests aberrant progesterone signalling contributes to TNBC risk, while preclinical studies indicate progesterone receptor modulators such as mifepristone may substantially reduce cancer development. DNA methylation-based markers reflecting field cancerization and replicative age could enable real-time monitoring of preventive efficacy and support an individualised primary prevention approach.