Haq Bushra, Geyer Charles E
Western Pennsylvania Hospital, The Western Pennsylvania Cancer Institute, Pittsburgh, PA 15224, USA.
Womens Health (Lond). 2009 Mar;5(2):135-47. doi: 10.2217/17455057.5.2.135.
Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18-23% of invasive breast carcinomas and is associated with a worse prognosis. This novel transforming gene was identified in 1985, and in 1987 HER2 amplification was demonstrated to be central to the aggressive, malignant phenotype of these cancers and a significant predictor of both time to relapse and overall survival. These observations led to the development of the first monoclonal antibody targeting the extracellular domain of HER2, trastuzumab (Herceptin, Genentech and Hoffman LaRoche, Switzerland), which was approved by the US FDA for metastatic breast cancer in 1998. In 2005, results from four major trastuzumab adjuvant trials demonstrated a marked reduction in risk of recurrence, and trastuzumab is now an essential component of the adjuvant treatment of HER2-positive early breast cancer. Concerns regarding cardiac safety and mechanisms of resistance to trastuzumab remain important issues and are being addressed in ongoing research efforts.
人表皮生长因子受体2（HER2）基因扩增存在于18% - 23%的浸润性乳腺癌中，且与较差的预后相关。这个新的转化基因于1985年被鉴定出来，1987年，HER2基因扩增被证明是这些癌症侵袭性恶性表型的核心，也是复发时间和总生存期的重要预测指标。这些观察结果促使了首个靶向HER2细胞外结构域的单克隆抗体——曲妥珠单抗（赫赛汀，基因泰克公司和瑞士罗氏公司）的研发，该药物于1998年被美国食品药品监督管理局批准用于治疗转移性乳腺癌。2005年，四项主要的曲妥珠单抗辅助治疗试验结果表明复发风险显著降低，曲妥珠单抗现在是HER2阳性早期乳腺癌辅助治疗的重要组成部分。关于心脏安全性和曲妥珠单抗耐药机制的问题仍然是重要课题，正在进行的研究工作中也在探讨这些问题。
