Medical Oncology Unit and Cancer Registry of Parma Province, University Hospital of Parma, Parma, Italy.
Cancer. 2011 May 1;117(9):1837-46. doi: 10.1002/cncr.25771. Epub 2010 Nov 10.
A series of retrospective studies have reported that patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are at a greater risk of central nervous system (CNS) metastases. Trastuzumab, which does not cross the blood-brain barrier, has been associated with this increased risk.
The authors evaluated incidence, survival, and risk factors for CNS metastases in the incident breast cancer population systematically collected by the Parma Province Cancer Registry over the 4-year period between 2004 and 2007.
A total of 1458 patients with a diagnosis of stage I to III invasive breast cancer were analyzed for study purposes. At a median follow-up of 4.1 years, CNS events were observed in 1.3% and 5% of HER2-negative patients and HER2-positive patients, respectively (P < .0001). The administration of trastuzumab either as adjuvant therapy or for metastatic disease was associated with a significantly increased risk of CNS involvement at first disease recurrence and after first extracranial recurrence, respectively. According to multivariate analysis, HER2-positive status and trastuzumab treatment, high Ki-67 index, and hormone receptor negativity remained independent risk factors for the development of CNS metastasis.
To the authors' knowledge, this is the first population-based cancer registry study analyzing factors associated with CNS recurrence in a general population of newly diagnosed breast cancer patients with known HER2 status. The data from the current study provide evidence that patients with HER2-positive breast cancer have a significantly higher incidence of CNS metastasis after treatment with trastuzumab. Improvements in systemic control and overall survival associated with trastuzumab-based therapy may lead to an "unmasking" of CNS disease recurrence that would otherwise remain clinically silent before a patient's death.
一系列回顾性研究报告称，人表皮生长因子受体 2（HER2）阳性乳腺癌患者发生中枢神经系统（CNS）转移的风险更高。曲妥珠单抗不能透过血脑屏障，与这种风险增加有关。
作者通过帕尔马省癌症登记处系统收集的 2004 年至 2007 年 4 年间的Ⅰ期至Ⅲ期浸润性乳腺癌患者资料，评估了该人群中 CNS 转移的发生率、生存情况和危险因素。
共分析了 1458 例诊断为Ⅰ期至Ⅲ期浸润性乳腺癌患者的资料。中位随访 4.1 年后，HER2 阴性和 HER2 阳性患者中分别有 1.3%和 5%发生 CNS 事件（P<0.0001）。辅助治疗或转移性疾病中使用曲妥珠单抗与首次疾病复发时和首次颅外复发后 CNS 受累的风险显著增加相关。多变量分析显示，HER2 阳性状态和曲妥珠单抗治疗、高 Ki-67 指数和激素受体阴性是 CNS 转移发展的独立危险因素。
据作者所知，这是第一项基于人群的癌症登记研究，分析了新诊断的 HER2 状态已知的乳腺癌患者一般人群中与 CNS 复发相关的因素。本研究的数据提供了证据，表明曲妥珠单抗治疗后，HER2 阳性乳腺癌患者发生 CNS 转移的发生率显著增加。曲妥珠单抗治疗带来的全身控制和总生存的改善可能导致 CNS 疾病复发的“显露”，否则患者在死亡前可能一直处于临床无症状状态。
