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<p>The emergence of antibody–drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), has redefined therapeutic strategies in metastatic breast cancer (mBC). Traditionally confined to HER2-positive disease (IHC&#xa0;3+ or IHC&#xa0;2+/ISH-positive), HER2-targeted therapies are now proving effective in HER2-low (IHC&#xa0;1+ or IHC&#xa0;2+/ISH-negative) disease and T‑DXd has even shown activity in tumours with ultralow (0+) HER2 expression. This short review summarizes a&#xa0;presentation from the 2025 annual conference of the Austrian Society of Haematology and Oncology focusing on the current and future role of ADCs in mBC, with particular emphasis on T‑DXd across the full spectrum of HER2 expression. A&#xa0;special focus is given to tolerability, efficacy in patients with brain metastases, and emerging novel standards in HER2-positive disease. As the role of ADCs expands across all breast cancer subtypes and treatment lines, the oncology community must balance efficacy with thoughtful patient selection and toxicity awareness.</p>

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The role of HER2-directed antibody–drug conjugates in the treatment of metastatic breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月8日

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  • Rupert Bartsch

摘要

The emergence of antibody–drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), has redefined therapeutic strategies in metastatic breast cancer (mBC). Traditionally confined to HER2-positive disease (IHC 3+ or IHC 2+/ISH-positive), HER2-targeted therapies are now proving effective in HER2-low (IHC 1+ or IHC 2+/ISH-negative) disease and T‑DXd has even shown activity in tumours with ultralow (0+) HER2 expression. This short review summarizes a presentation from the 2025 annual conference of the Austrian Society of Haematology and Oncology focusing on the current and future role of ADCs in mBC, with particular emphasis on T‑DXd across the full spectrum of HER2 expression. A special focus is given to tolerability, efficacy in patients with brain metastases, and emerging novel standards in HER2-positive disease. As the role of ADCs expands across all breast cancer subtypes and treatment lines, the oncology community must balance efficacy with thoughtful patient selection and toxicity awareness.