Summary: The confirmation of the HER2-low paradigm is expected to have a major impact in breast oncology. About half of all breast cancers harbor HER2-low expression, which can be targeted with the anti-HER2 antibody–drug conjugate trastuzumab deruxtecan (T-DXd), leading to a relevant survival benefit in the metastatic setting. Given this observation, treatment algorithms for both hormone receptor–positive and triple-negative breast cancer are expected to significantly evolve in the next future. Several challenges, however, remain in the interpretation of HER2-low expression related to its biological role, its pathologic diagnosis, and the definition itself of HER2-low. In this article, we recapitulate the current knowledge on HER2-low breast cancer, discussing whether it should be considered a distinct subtype, how it should be implemented in the clinic, and how its definition may evolve in the coming years with the evolution of our clinical and translational knowledge.

中文翻译：

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探索乳腺肿瘤学中 HER2-Low 范式：新标准，未来视野

摘要：HER2-low 范式的确认预计将对乳腺肿瘤学产生重大影响。大约一半的乳腺癌存在 HER2 低表达，可以使用抗 HER2 抗体药物偶联物曲妥珠单抗 deruxtecan (T-DXd) 进行靶向治疗，从而在转移性环境中带来相关的生存获益。鉴于这一观察结果，激素受体阳性和三阴性乳腺癌的治疗算法预计将在未来显着发展。然而，对 HER2-low 表达的解释仍存在一些挑战，包括其生物学作用、病理诊断以及 HER2-low 的定义本身。在本文中，我们概述了当前关于 HER2 低乳腺癌的知识，讨论是否应将其视为一种独特的亚型，