HER2-targeted therapies for patients with HER2⁺ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2⁺ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2⁺ breast cancer.

针对 HER2⁺ 乳腺癌患者的 HER2 靶向疗法正在迅速发展，提供了一系列更复杂和个性化的治疗方案。目前，在治愈和姑息治疗的情况下，使用一系列抗 HER2 单克隆抗体、酪氨酸激酶抑制剂和抗体-药物偶联物，有时与化疗或内分泌治疗一起给药。然而，HER2⁺ 乳腺癌的异质性需要更深入地了解疾病生物学及其在响应新型 HER2 靶向药物和非 HER2 靶向治疗中的作用，以优化患者预后。在本综述中，我们重新审视了 HER2 靶向药物的作用机制，研究了支持在 HER2 扩增肿瘤患者中使用双重 HER2 阻断的证据，并探讨了生物标志物在指导未来治疗策略中的作用。我们还讨论了对 HER2⁺ 乳腺癌患者未来治疗的潜在影响。