The management of human epidermal growth factor receptor (HER2)–positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2‐targeted therapies for the treatment of early‐stage and/or advanced‐stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2‐positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2‐positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de‐escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2‐positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2‐positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2‐positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2‐positive BC going forward.

中文翻译：

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HER2 阳性乳腺癌治疗的护理标准和新挑战

在过去的 20 年中，人类表皮生长因子受体 (HER2) 阳性乳腺癌 (BC) 的管理迅速发展。重大进展导致美国食品和药物管理局批准了 7 种 HER2 靶向疗法用于治疗早期和/或晚期疾病。尽管肿瘤结果不断改善，但大多数晚期 HER2 阳性 BC 患者最终因治疗原发或获得性耐药而死于疾病，而术前全身治疗后残留浸润性疾病的 HER2 阳性早期 BC 患者处于较高水平。远处复发和死亡的风险。治疗降级和升级的概念对于为 HER2 阳性 BC 患者优化定制治疗越来越重要，并且是当前审查的主要焦点。讨论了这方面的研究工作以及有关（新）辅助和转移性环境中不断发展的护理标准的更新，包括使用新型联合疗法。作者还简要讨论了 HER2 阳性 BC 管理中的持续挑战（例如，内在与获得性耐药性、预测性生物标志物的识别、成像技术的整合以指导临床实践）以及 HER2 阳性脑转移的治疗. 旨在克服这些挑战的研究对于确保 HER2 阳性 BC 管理的持续进展势在必行。作者还简要讨论了 HER2 阳性 BC 管理中的持续挑战（例如，内在与获得性耐药性、预测性生物标志物的识别、成像技术的整合以指导临床实践）以及 HER2 阳性脑转移的治疗. 旨在克服这些挑战的研究对于确保 HER2 阳性 BC 管理的持续进展势在必行。作者还简要讨论了 HER2 阳性 BC 管理中的持续挑战（例如，内在与获得性耐药性、预测性生物标志物的识别、影像学技术的整合以指导临床实践）以及 HER2 阳性脑转移瘤的治疗. 旨在克服这些挑战的研究对于确保 HER2 阳性 BC 管理的持续进展势在必行。