Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma
Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma
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DOI：
10.1002/cncr.11436
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发表时间：
2003-06-15
期刊：
影响因子：
6.2
通讯作者：
Winer, E
中科院分区：
文献类型：
--
作者：
Bendell, JC;Domchek, SM;Winer, E
背景HER-2过表达的转移性乳腺癌患者可从曲妥珠单抗治疗中获益，但曲妥珠单抗不能穿过血脑屏障。作者描述了这些妇女的中枢神经系统（CNS）疾病。使用药房记录，作者回顾性地确定了1998年6月至2000年12月在Dana-Farber Partners Cancer Care接受单独曲妥珠单抗或化疗治疗HER-2阳性转移性乳腺癌的153名女性。在排除未进行充分临床随访或曲妥珠单抗治疗前患有CNS疾病的患者后，确定了一个包含122例患者的研究队列。中枢神经系统疾病定义为一个或多个脑转移瘤或软脑膜癌病。该队列的中位随访时间为23个月。34%的患者（95%置信区间，26-44%）在转移性乳腺癌诊断后中位16个月和曲妥珠单抗治疗开始后6个月发现中枢神经系统转移。93%的CNS疾病患者出现临床症状。5%的CNS疾病患者仅累及软脑膜，尽管14%的患者累及软脑膜并伴有脑实质转移。在诊断CNS转移时，50%的患者在其他疾病部位接受曲妥珠单抗治疗时有反应或病情稳定。CNS转移后的中位生存期为13个月。50%的患者死于进行性CNS疾病。接受曲妥珠单抗作为转移性疾病一线治疗的患者在其他疾病部位对曲妥珠单抗有效或稳定时经常发生脑转移。CNS转移性乳腺癌在接受曲妥珠单抗治疗的患者中很常见，包括对CNS外治疗有反应的患者。这可能是由于HER-2阳性肿瘤细胞对CNS的偏好和/或曲妥珠单抗对CNS的渗透性较差，或者是由于内脏疾病控制改善导致寿命延长和晚期肿瘤扩散至CNS的发生。可能需要努力表征CNS疾病发展的其他风险因素、最佳筛查算法和新的治疗策略。(C)2003年美国癌症协会。
BACKGROUND. Women with HER-2 overexpressing metastatic breast carcinoma benefit from trastuzumab-based therapy, but trastuzumab does not cross the blood-brain barrier. The authors characterized central nervous system (CNS) disease in these women.METHODS. Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER-2-positive metastatic breast carcinoma at Dana-Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow-up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow-up of this cohort was 23 months.RESULTS. Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26-44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety-three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first-line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites.CONCLUSIONS. Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab-based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER-2-positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted. (C) 2003 American Cancer Society.