Lamond Nathan Wd, Younis Tallal
Department of Medicine, Dalhousie University at the Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
Int J Womens Health. 2014 May 16;6:509-21. doi: 10.2147/IJWH.S47357. eCollection 2014.
In the absence of specific therapy, the 15%-20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin), the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab's clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab's incorporation into clinical practice.
在缺乏特异性治疗的情况下，15% - 20%的乳腺癌表现出人表皮生长因子受体2（HER2）蛋白过表达和/或基因扩增，与HER2阴性的乳腺癌相比，其具有更具侵袭性的表型和更差的预后。曲妥珠单抗（赫赛汀）是第一种抗HER2靶向治疗药物，已使HER2阳性乳腺癌患者的生存结果得到改善。然而，许多早期疾病患者仍会复发，转移性疾病仍然无法治愈。为了进一步改善这些结果，最近已开发出几种新型HER2靶向药物。帕妥珠单抗（帕捷特）是一种针对HER2二聚化结构域的单克隆抗体，在临床试验中也与患者生存结果的改善相关，最近已被批准与化疗和曲妥珠单抗联合用于早期HER2阳性乳腺癌的新辅助治疗以及转移性疾病的一线治疗。本综述简要总结了帕妥珠单抗的临床研发情况以及支持其使用的已发表证据，并强调了一些目前尚未解决的问题，这些问题将影响帕妥珠单抗纳入临床实践。
