A multidisciplinary team led by Deborah Utjés, MD, Department for Women's and Children's Health, Karolinska Institutet, and Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden and colleagues argued in The Lancet Oncology that mifepristone, best known for its role in medical abortion, may warrant renewed investigation as a preventive option for women at high risk of breast cancer.
The authors noted current strategies for BRCA1 or BRCA2 carriers remain limited to surgery—mastectomy or oophorectomy—or selective estrogen receptor modulators (SERMs), of which only tamoxifen is approved for premenopausal women. However, SERMs have not been shown to reduce breast cancer-specific mortality and are largely ineffective against triple-negative breast cancer, the dominant subtype in BRCA1 carriers.
At a 2024 consensus workshop in Innsbruck, Austria, researchers identified progesterone as a key driver of carcinogenesis. BRCA1 carriers were shown to have abnormally high progesterone levels, fueling luminal progenitor cell expansion and risk of aggressive disease.
Three small studies examined mifepristone’s effects:
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In premenopausal women with healthy breast tissue, the drug significantly reduced epithelial proliferation, lowering Ki-67 expression
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In BRCA1/2 carriers, it reduced luminal progenitor cell populations and decreased epigenetic markers of mitogenic age
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A transcriptomic analysis showed extracellular matrix–remodeling signatures linked to progesterone-driven carcinogenesis
Despite these early findings, the authors noted that research has been stymied by political and regulatory barriers given mifepristone’s association with abortion care, lack of regulatory separation between reproductive and non-reproductive users, and limited industry investment. They urged that larger preclinical and early-phase trials are needed to test safety and efficacy, calling the drug a potential non-surgical prevention strategy for women at the highest genetic risk.
Full disclosures can be found in the published viewpoint.
Source: The Lancet Obstetrics, Gynaecology, & Women’s Health
