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<p>Women with germline <i>BRCA1</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月25日

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  • Martin Widschwendter,
  • Rita Schmutzler,
  • Nora Pashayan,
  • Jelle Wesseling,
  • Marc Tischkowitz,
  • Michal Zikan,
  • Miranda Steenbeek,
  • Marike Gabrielson,
  • Christian F. Singer,
  • Cathrin Brisken,
  • Rebecca Gomperts,
  • Sharon Cameron,
  • Dafydd Gareth Evans,
  • Andri Papakonstantinou,
  • Marc Buyse,
  • Kerstin Rhiem,
  • Mateja Krajc,
  • Charlotte Vavourakis,
  • Elisa Redl,
  • Chiara Herzog,
  • James Barrett,
  • Mohammed Fatih Rasul,
  • Deborah Utjés,
  • Kiriaki Papaikonomou,
  • Angelique Flöter Rådestad,
  • Athanasios Zouzos,
  • Twana Alkasalias,
  • Kristina Gemzell-Danielsson

摘要

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.