HER2作为一个可行和高度敏感的治疗靶标的长期寻找终于实现了，这是治疗高侵袭性HER2阳性乳腺癌的一个重大突破，而且已近25年前批准了第一个HER2定向药物——单克隆抗体曲妥珠单抗。自那时以来，人们对定向HER2的单克隆抗体、酪氨酸激酶抑制剂和抗体药物偶联物在多项试验中所展现出的卓越临床活性有了迅速的进展，诱发了广泛的努力，以开发更新的平台和更有针对性的治疗方法。本综述讨论了HER2阳性乳腺癌的当前治疗标准，抵抗HER2定向治疗的机制以及新的治疗方法和药物，包括利用免疫系统的策略。 ©2022 Springer Nature Limited.

The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug - the monoclonal antibody trastuzumab - almost 25 years ago. Since then, progress has been swift and the impressive clinical activity across multiple trials with monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates that target HER2 has spawned extensive efforts to develop newer platforms and more targeted therapies. This Review discusses the current standards of care for HER2-positive breast cancer, mechanisms of resistance to HER2-targeted therapy and new therapeutic approaches and agents, including strategies to harness the immune system.© 2022. Springer Nature Limited.