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.

人们长期以来一直寻求发现 HER2 作为一种可行且高度敏感的治疗靶点，这是治疗高度侵袭性 HER2 阳性乳腺癌的重大突破，导致第一个 HER2 靶向药物——单克隆抗体曲妥珠单抗——在近 25 年来获得批准前。从那时起，进展迅速，针对 HER2 的单克隆抗体、酪氨酸激酶抑制剂和抗体药物偶联物的多项试验取得了令人印象深刻的临床活动，促使人们广泛努力开发更新的平台和更有针对性的疗法。本综述讨论了 HER2 阳性乳腺癌的现行治疗标准、HER2 靶向治疗的耐药机制以及新的治疗方法和药物，包括利用免疫系统的策略。