Tokunaga Eriko, Oki Eiji, Nishida Kojiro, Koga Tadashi, Egashira Akinori, Morita Masaru, Kakeji Yoshihiro, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Int J Clin Oncol. 2006 Jun;11(3):199-208. doi: 10.1007/s10147-006-0575-4.
The emergence of trastuzumab has drastically changed therapy for breast cancer. Trastuzumab (Herceptin; Genentech) is a recombinant humanized monoclonal antibody that targets an epitope in the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. HER2 is a member of a family of four transmembrane receptor tyrosine kinases that regulate cell growth, survival, and differentiation via multiple signal transduction pathways. Overexpression of HER2 or amplification of the HER2 gene occurs in 20%-30% of human breast cancers. Preclinical models have demonstrated that this antibody has significant antitumor activity as a single agent, and it also has a synergy with certain chemotherapeutic drugs. Phase II and III clinical trials performed in women with metastatic breast cancers that overexpress HER2 have shown trastuzumab to have clinical activity when used as monotherapy, while also improving survival when used as a first-line therapy in combination with chemotherapy. At present, clinical investigations are focusing attention on the efficacy of trastuzumab in both the adjuvant and neoadjuvant setting, as well as in the metastatic setting. In this review, we describe the developments and current status of trastuzumab-based treatment for breast cancer.
曲妥珠单抗的出现极大地改变了乳腺癌的治疗方式。曲妥珠单抗（赫赛汀；基因泰克公司）是一种重组人源化单克隆抗体，靶向人表皮生长因子受体2（HER2）蛋白细胞外结构域中的一个表位。HER2是一个由四个跨膜受体酪氨酸激酶组成的家族成员，通过多种信号转导途径调节细胞生长、存活和分化。20% - 30%的人类乳腺癌中存在HER2过表达或HER2基因扩增。临床前模型表明，这种抗体作为单一药物具有显著的抗肿瘤活性，并且还与某些化疗药物具有协同作用。在HER2过表达的转移性乳腺癌女性患者中进行的II期和III期临床试验表明，曲妥珠单抗作为单药治疗具有临床活性，同时与化疗联合作为一线治疗时还能提高生存率。目前，临床研究正关注曲妥珠单抗在辅助和新辅助治疗以及转移性治疗中的疗效。在本综述中，我们描述了基于曲妥珠单抗的乳腺癌治疗的进展和现状。
