Approximately 80% of invasive breast cancers are classified as human epidermal growth factor receptor 2 (HER2)-negative; however, many of these tumors have detectable levels of HER2 surface expression. Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate with a membrane-permeable payload that is cytotoxic to both HER2-expressing tumor cells and neighboring cells via the bystander antitumor effect. T-DXd has shown significant antitumor activity in clinical trials for patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) breast cancer. In addition, the results of the DESTINY-Breast04 trial demonstrated the clinical benefit of T-DXd in patients with HER2-low (IHC 1+ or IHC 2+/ISH−) breast cancer after receiving prior chemotherapy. DESTINY-Breast06 demonstrated the clinical benefit of T-DXd in patients with hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH−), and HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer who had not received prior chemotherapy in the advanced setting. These results validate the need for a standard-of-care diagnostic test to identify HER2-low and HER2-ultralow expression levels in patients with metastatic breast cancer to guide therapeutic decision-making. Furthermore, effective treatment sequencing strategies and adverse event management are essential for maximizing patient benefit. This review presents the identification of HER2-low and HER2-ultralow breast cancer, sequencing of T-DXd with other treatments, and management of common or clinically significant adverse events reported with T-DXd.
约80%的浸润性乳腺癌被归类为人表皮生长因子受体2（HER2）阴性；然而，这些肿瘤中有许多仍可检测到HER2表面表达。Trastuzumab deruxtecan（T-DXd）是一种靶向HER2的抗体药物偶联物，其有效载荷具有膜渗透性，可通过旁观者抗肿瘤效应对表达HER2的肿瘤细胞及邻近细胞产生细胞毒性。在针对HER2阳性（免疫组化[IHC] 3+或IHC 2+/原位杂交[ISH]+）乳腺癌患者的临床试验中，T-DXd已显示出显著的抗肿瘤活性。此外，DESTINY-Breast04试验结果证实了T-DXd在既往接受过化疗的HER2低表达（IHC 1+或IHC 2+/ISH−）乳腺癌患者中的临床获益。DESTINY-Breast06试验则证明了T-DXd在激素受体（HR）阳性、HER2低表达（IHC 1+或IHC 2+/ISH−）及HER2极低表达（IHC 0伴膜染色）且晚期阶段未接受过化疗的转移性乳腺癌患者中的临床获益。这些结果证实了建立标准化诊断检测的必要性，以识别转移性乳腺癌患者的HER2低表达和极低表达水平，从而指导治疗决策。此外，有效的治疗序贯策略和不良事件管理对于最大化患者获益至关重要。本综述将阐述HER2低表达与极低表达乳腺癌的识别、T-DXd与其他治疗的序贯应用，以及T-DXd常见或具有临床意义的不良事件管理。
肿瘤(癌症)患者之家