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.
Authors
- Elisa Redl (ORCID: https://orcid.org/0000-0001-6540-8443)
- Andri Papakonstantinou (ORCID: https://orcid.org/0000-0002-4232-4658)
- Twana Alkasalias (ORCID: https://orcid.org/0000-0003-4567-2364)
- Martin Widschwendter (ORCID: https://orcid.org/0000-0002-7778-8380)
- Miranda Steenbeek
- Mohammed Fatih Rasul (ORCID: https://orcid.org/0000-0003-4742-230X)
- M Buyse
- Marike Gabrielson (ORCID: https://orcid.org/0000-0002-3171-1556)
- M Zikan
- Kiriaki Papaikonomou (ORCID: https://orcid.org/0000-0002-0862-6265)
- Athanasios Zouzos (ORCID: https://orcid.org/0000-0003-2654-827X)
- Cathrin Brisken (ORCID: https://orcid.org/0000-0002-6857-3230)
- Deborah Utjés (ORCID: https://orcid.org/0000-0002-7335-8017)
- Christian F. Singer
- Kristina Gemzell- Danielsson
- D Gareth Evans
- Rita Schmutzler
- Sharon Cameron
- James Barrett
- Charlotte Vavourakis
- Rebecca Gomperts
- Chiara Herzog
- Marc Tischkowitz
- Nora Pashayan
- Kerstin Rhiem
- Mateja Krajc
- Angelique Flöter Rådestad
- Jelle Wesseling
Institutions
- NHS Lothian (GB)
- Karolinska University Hospital (SE)
- Radboud University Nijmegen (NL)
- University of Cologne (DE)
- Universität Innsbruck (AT)
- Charles University (CZ)
- University of Cambridge (GB)
- Breast Cancer Now (GB)
- Leiden University Medical Center (NL)
- Radboud University Medical Center (NL)
- Karolinska Institutet (SE)
- University of Manchester (GB)
- Institute of Oncology Ljubljana (SI)
- National Institute for Health and Care Research (GB)
- International Drug Development Institute (Belgium) (BE)
- Oncode Institute (NL)
- MRC Centre for Reproductive Health (GB)
- Tirol Kliniken (AT)
- Atria (NL)
- University Hospital Cologne (DE)
- University College London (GB)
- Salahaddin University-Erbil (IQ)
- École Polytechnique Fédérale de Lausanne (CH)
- Medical University of Vienna (AT)
- Tishk International University (IQ)
- Cancer Council Australia (AU)
- Cancer Council NSW (AU)
- University of Edinburgh (GB)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1038/s41523-026-00998-x
- Primary Topic
- BRCA gene mutations in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00