Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Cancer Treat Rev. 2014 Mar;40(2):259-70. doi: 10.1016/j.ctrv.2013.09.002. Epub 2013 Sep 11.
Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15-20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.
A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.
This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.
Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective.
人表皮生长因子受体 2（HER2）在 15-20%的所有乳腺癌中过表达。曲妥珠单抗的治疗导致了 HER2 阳性乳腺癌患者的结局改善和生存时间延长，并且该药物目前已成为辅助和转移性环境中的标准治疗方法。然而，曲妥珠单抗耐药很常见，因此针对 HER2 阳性乳腺癌的治疗重点是开发能够增强曲妥珠单抗效果或针对对曲妥珠单抗耐药的细胞的治疗药物。本综述探讨了 HER2 阳性乳腺癌中双重靶向治疗的疗效和毒性。
使用 PubMed 进行了基于计算机的文献检索；包括国际会议和 clinicaltrials.gov 上报告的数据。
本文描述了拉帕替尼、帕妥珠单抗或曲妥珠单抗-DM1 与曲妥珠单抗联合用于（新）辅助和转移性环境中的疗效和安全性。此外，还描述了针对下游途径的药物与曲妥珠单抗的联合治疗。
双重阻断可能代表了 HER2 阳性乳腺癌患者的重大进展。然而，相关的亚组仍有待确定，包括心脏毒性在内的副作用可能是使用的限制因素。迫切需要前瞻性生物标志物驱动的试验来确定哪些患者对双重靶向治疗具有成本效益。
