Duchnowska Renata, Szczylik Cezary
Department of Oncology, Military Institute of Medicine, Ul. Szaserów 128, 00-909 Warsaw, Poland.
Cancer Treat Rev. 2005 Jun;31(4):312-8. doi: 10.1016/j.ctrv.2005.04.008.
Amplification or over-expression of the HER2/neu receptor is present in 20-30% of invasive breast cancers and in 60% of intraductal breast carcinomas. Patients with HER2/neu gene aberrations have more aggressive disease, frequent disease recurrence and a shorter survival. Trastuzumab (herceptin) is a monoclonal antibody selectively directed against the HER2/neu receptor. The addition of trastuzumab to chemotherapy in HER2/neu-positive advanced breast cancer patients has increased complete and partial response rates, and prolonged time to progression and overall survival. However, a relatively common failure site in patients administered trastuzumab is the central nervous system (CNS). CNS metastases in these patients seem to develop despite responses achieved in extracerebral sites. This pattern of failure has mainly been attributed to the lack of trastuzumab penetration to the CNS owing to the high molecular weight (145 kDa) of this molecule. Additionally, increased risk of CNS relapse may be associated with improved systemic control of extracerebral metastases and prolonged survival without brain protection (a sanctuary site). Finally, it was postulated that HER2/neu over-expression and/or amplification might predispose to brain metastases. The aim of this article is to discuss the pathophysiology of this phenomenon and its clinical implications.
HER2/neu受体的扩增或过表达存在于20%-30%的浸润性乳腺癌以及60%的乳腺导管内癌中。HER2/neu基因异常的患者疾病侵袭性更强，疾病复发频繁，生存期较短。曲妥珠单抗（赫赛汀）是一种选择性针对HER2/neu受体的单克隆抗体。在HER2/neu阳性的晚期乳腺癌患者中，将曲妥珠单抗添加到化疗方案中可提高完全缓解率和部分缓解率，并延长疾病进展时间和总生存期。然而，接受曲妥珠单抗治疗的患者中一个相对常见的失败部位是中枢神经系统（CNS）。尽管脑外部位取得了缓解，但这些患者仍会发生CNS转移。这种失败模式主要归因于该分子分子量高（145 kDa），曲妥珠单抗无法穿透进入CNS。此外，CNS复发风险增加可能与脑外转移的全身控制改善以及无脑部保护（一个庇护部位）的生存期延长有关。最后，有人推测HER2/neu过表达和/或扩增可能易发生脑转移。本文的目的是讨论这一现象的病理生理学及其临床意义。
