Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Spain.
Breast. 2018 Jun;39:80-88. doi: 10.1016/j.breast.2018.03.006. Epub 2018 Apr 6.
Since the identification of the HER2 receptor amplification as an adverse prognostic factor that defined a special subtype of metastatic breast cancer, there has been a substantial improvement in survival of patients affected with this disease due to the development of anti-HER2 targeted therapies. The approval of trastuzumab and pertuzumab associated to a taxane in first line and subsequent treatment with the antibody-drug conjugate T-DM1 has certainly contributed to achieve these outcomes. The Tyrosine Kinase Inhibitor lapatinib was also approved in the basis of an improvement in progression free survival, becoming another commonly used treatment in combination with capecitabine. Inevitably, despite these therapeutic advances most patients progress on therapy due to primary or acquired resistance or because of an incorrect HER2 positivity assessment. Hence, it is crucial to correctly categorize HER2 amplified tumors and define mechanisms of resistance to design effective new treatment approaches. In addition, identifying biomarkers of response or resistance permits to tailor the therapeutic options for each patient sparing them from unnecessary toxicity as well as improving their outcomes. The aim of this review is to examine new strategies in development to treat HER2-positive metastatic breast cancer referring to the mechanisms of action of new drugs and new combinations including results reported so far.
自 HER2 受体扩增被确定为不良预后因素，并定义了转移性乳腺癌的一种特殊亚型以来，由于抗 HER2 靶向治疗的发展，患有这种疾病的患者的生存率有了显著提高。曲妥珠单抗和帕妥珠单抗与紫杉烷联合用于一线治疗，随后使用抗体药物偶联物 T-DM1 进行后续治疗，这肯定有助于实现这些结果。酪氨酸激酶抑制剂拉帕替尼也因其无进展生存期的改善而获得批准，成为另一种与卡培他滨联合使用的常用药物。不可避免的是，尽管有这些治疗进展，但大多数患者由于原发性或获得性耐药或由于 HER2 阳性评估不正确而在治疗中进展。因此，正确分类 HER2 扩增肿瘤并确定耐药机制对于设计有效的新治疗方法至关重要。此外，鉴定反应或耐药的生物标志物可以为每个患者量身定制治疗方案，避免不必要的毒性，并改善他们的预后。本综述的目的是研究开发中的新策略，以治疗 HER2 阳性转移性乳腺癌，参考新药和新联合用药的作用机制，包括迄今为止报告的结果。
