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<p>The hormone-receptor positive/human epidermal growth factor receptor&#xa0;2 negative (HR+/HER2−) metastatic breast cancer represents the most common subgroup of advanced breast cancers. Targeted therapies, including cyclin-dependent kinases (CDK) 4/6&#xa0;inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, and phosphatidylinositol-3-kinase (PI3K) inhibitors, have significantly extended progression-free survival (PFS), while new antibody–drug conjugates (ADCs) such as trastuzumab deruxtecan and sacituzumab govitecan offer clinically meaningful benefits, particularly in endocrine-resistant or HER2-low tumors. Molecular markers such as <i>ESR1</i> and <i>PIK3CA</i> mutations, as well as <i>BRCA&#xa0;1/2</i> germline mutations increasingly enable personalized therapeutic approaches. However, questions remain regarding therapy sequencing, cross-resistances, and optimal application strategies, underscoring the importance of translational research and precision medicine to further improve patient outcomes.</p>

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Metastasiertes hormonrezeptorpositives Mammakarzinom – die Qual der Wahl

  • 期刊论文

  • 发表日期：

    2025年4月11日

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  • Marion T. van Mackelenbergh,
  • Michael Friedrich,
  • Nicolai Maass

摘要

The hormone-receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) metastatic breast cancer represents the most common subgroup of advanced breast cancers. Targeted therapies, including cyclin-dependent kinases (CDK) 4/6 inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, and phosphatidylinositol-3-kinase (PI3K) inhibitors, have significantly extended progression-free survival (PFS), while new antibody–drug conjugates (ADCs) such as trastuzumab deruxtecan and sacituzumab govitecan offer clinically meaningful benefits, particularly in endocrine-resistant or HER2-low tumors. Molecular markers such as ESR1 and PIK3CA mutations, as well as BRCA 1/2 germline mutations increasingly enable personalized therapeutic approaches. However, questions remain regarding therapy sequencing, cross-resistances, and optimal application strategies, underscoring the importance of translational research and precision medicine to further improve patient outcomes.