Kataoka Akemi, Ishida Mayumi, Murakami Shigeru, Ohno Shinji
Department of Breast Oncology, National Hospital Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan.
Breast Cancer. 2004;11(2):105-15. doi: 10.1007/BF02968288.
This article reviews the current state of efforts targeting human epidermal growth factor receptor-2 (erbB2/HER2)in breast cancer therapy. The results of recently conducted clinical studies with trastuzumab and several other compounds are presented. Trastuzumab, a humanised monoclonal antibody(mAb)directed against the extracellular domain of HER2, has been shown to be active against HER2-overexpressing metastatic breast cancer, either as a single agent or when used in combination with chemotherapy. In preclinical models, trastuzumab has shown additive and even synergistic anti-tumor activity with the chemotherapeutic agents. In a large, randomised, phase III trial, the combination of trastuzumab and chemotherapy was shown to improve the response rate and survival in patients with metastatic breast cancer. The high incidence of cardiotoxicity seen with the combination of trastuzumab plus anthracycline drugs prompted several clinical studies combining trastuzumab with other chemotherapeutic agents, including taxanes, vinorelbine and platinum salts. This article summarises the available data on trastuzumab-based combination chemotherapies and novel drugs targeting HER2 and signal transduction molecules for the treatment of breast cancer.
本文综述了乳腺癌治疗中针对人表皮生长因子受体2（erbB2/HER2）的研究现状。文中介绍了近期使用曲妥珠单抗及其他几种化合物进行的临床研究结果。曲妥珠单抗是一种针对HER2细胞外结构域的人源化单克隆抗体（mAb），已被证明对HER2过表达的转移性乳腺癌有效，可单独使用或与化疗联合使用。在临床前模型中，曲妥珠单抗已显示出与化疗药物具有相加甚至协同的抗肿瘤活性。在一项大型随机III期试验中，曲妥珠单抗与化疗联合使用可提高转移性乳腺癌患者的缓解率并延长生存期。曲妥珠单抗与蒽环类药物联合使用时观察到的高心脏毒性发生率促使开展了多项将曲妥珠单抗与其他化疗药物联合使用的临床研究，这些化疗药物包括紫杉烷类、长春瑞滨和铂盐。本文总结了基于曲妥珠单抗的联合化疗以及靶向HER2和信号转导分子的新型药物治疗乳腺癌的现有数据。
