Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer.
Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer.
复制标题
DOI：
10.2147/bctt.s90627
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Moreno-Aspitia A
中科院分区：
文献类型：
--
作者：
Advani P;Cornell L;Chumsri S;Moreno-Aspitia A
人表皮生长因子受体2（HER 2）是一种酪氨酸激酶跨膜受体，在15%-20%的乳腺肿瘤表面过表达，与预后不良相关。在早期和晚期乳腺癌中，曲妥珠单抗联合标准化疗可持续改善病理缓解和生存率。然而，对曲妥珠单抗的耐药性可能是有效治疗HER 2阳性乳腺癌的主要问题。双重HER 2阻断，使用与曲妥珠单抗互补的药物，最近已被探索以避免术前（新辅助）和辅助治疗中的耐药性。最近在临床研究中报告了双重抗HER 2药物相对于单一阻断剂的有效性增加。帕妥珠单抗联合曲妥珠单抗和紫杉烷目前已获批用于HER 2阳性乳腺癌的转移性和新辅助治疗。还研究了各种生物标志物，以确定可能对这些靶向治疗组合反应最佳的HER 2阳性肿瘤患者亚组。在这篇文章中，已经审查了关于新辅助和辅助治疗中联合HER 2药物治疗的疗效和毒性的现有试验数据，并讨论了这些试验的相关生物标志物数据。
Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase transmembrane receptor that is overexpressed on the surface of 15%–20% of breast tumors and has been associated with poor prognosis. Consistently improved pathologic response and survival rates have been demonstrated with use of trastuzumab in combination with standard chemotherapy in both early and advanced breast cancer. However, resistance to trastuzumab may pose a major problem in the effective treatment of HER2-positive breast cancer. Dual HER2 blockade, using agents that work in a complimentary fashion to trastuzumab, has more recently been explored to evade resistance in both the preoperative (neoadjuvant) and adjuvant settings. Increased effectiveness of dual anti-HER2 agents over single blockade has been recently reported in clinical studies. Pertuzumab in combination with trastuzumab and taxane is currently approved in the metastatic and neoadjuvant treatment of HER2-positive breast cancer. Various biomarkers have also been investigated to identify subsets of patients with HER2-positive tumors who would likely respond best to these targeted therapy combinations. In this article, available trial data regarding efficacy and toxicity of treatment with combination HER2 agents in the neoadjuvant and adjuvant setting have been reviewed, and relevant correlative biomarker data from these trials have been discussed.