Treatment of HER2-positive metastatic breast cancer following initial progression.
Treatment of HER2-positive metastatic breast cancer following initial progression.
复制标题
DOI：
10.3816/cbc.2009.s.005
复制
发表时间：
2009-06
影响因子：
3.1
通讯作者：
Mayer IA
中科院分区：
文献类型：
--
作者：
Mayer IA
分子靶向治疗的重大进展为her2过表达转移性乳腺癌患者提供了更有效、侵袭性更低的治疗形式。尽管在这种情况下进行的许多治疗性随机试验最初取得了令人鼓舞的结果，但曲妥珠单抗（首个在这种情况下显示出显著活性的抗her2单克隆抗体）的新生和获得性耐药可能会发生。由于最近的研究强烈支持曲妥珠单抗不仅在转移性疾病的治疗中发挥作用，而且在her2过表达乳腺癌的辅助治疗中也发挥作用，曲妥珠单抗耐药的临床问题正变得越来越重要。对于her2过表达转移性疾病的最佳治疗方法的具体建议具有挑战性，因为该领域已经取得了相当大的进展。本文将回顾在转移性情况下抗her2治疗决策时需要考虑的一些要点：(1)在一线含曲妥珠单抗方案进展后继续使用曲妥珠单抗的益处；(2)最近添加的新药物可用于治疗her2过表达的乳腺癌；(3)导致曲妥珠单抗耐药的分子机制。这些问题在确定新的治疗靶点以增加对曲妥珠单抗治疗的反应程度和持续时间方面是必不可少的。
Significant advances in molecular-targeted therapies have provided more effective and less aggressive forms of therapy for patients with HER2-overexpressing metastatic breast cancers. Despite the initial encouraging results of many therapeutic randomized trials that have been undertaken in this setting, de novo and acquired resistance to trastuzumab, the first anti-HER2 monoclonal antibody to demonstrate significant activity in this setting, can occur. Because recent studies strongly support a role for trastuzumab in not only the management of metastatic disease but also the adjuvant setting for HER2-overexpressing breast cancers, the clinical problem of trastuzumab resistance is becoming increasingly important. Specific recommendations for the optimal treatment of HER2-overexpressing metastatic disease are challenging because considerable advances in the field have been made. This article will review some of the main points to be considered for decision-making in anti-HER2 treatment in the metastatic setting: (1) the benefit of continued trastuzumab after progression on a first-line trastuzumab-containing regimen, (2) novel agents that have been recently added to the plethora of drugs available to treat HER2-overexpressing breast cancers, and (3) molecular mechanisms that contribute to trastuzumab resistance. These issues are imperative in identifying novel therapeutic targets with the goal of increasing the magnitude and duration of response to trastuzumab-based treatment.