Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy
Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy
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DOI：
10.1093/annonc/mdi371
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发表时间：
2005-11-01
影响因子：
50.5
通讯作者：
Klein, P
中科院分区：
文献类型：
--
作者：
Burstein, HJ;Lieberman, G;Klein, P
用途：本研究的目的是描述接受曲妥珠单抗治疗的HER 2过表达转移性乳腺癌女性患者中枢神经系统（CNS）转移的患病率和预测因素。在HER 2阳性转移性乳腺癌患者中，在两项临床试验中接受化疗联合或不联合曲妥珠单抗作为转移性疾病的一线治疗。第一项试验是化疗（多柔比星/环磷酰胺或紫杉醇）+/-曲妥珠单抗的多中心随机III期研究，第二项试验是长春瑞滨+曲妥珠单抗的多中心II期试验。所有患者都有可测量的疾病，并在开始研究treatment.Results：近10%的患者接受曲妥珠单抗联合化疗开发孤立的中枢神经系统转移作为第一个网站的肿瘤进展的症状性中枢神经系统疾病。在接受基于曲妥珠单抗治疗的女性中，CNS进展往往晚于其他部位的进展。基于曲妥珠单抗的治疗并未显著延迟CNS转移（作为初始进展部位）的发生。在诊断为原发性乳腺癌后，与缺乏基因扩增的肿瘤相比，HER 2基因扩增的肿瘤往往与更大的孤立性CNS进展风险相关。HER 2过表达转移性乳腺癌患者存在孤立性CNS进展风险，反映了通过使用基于曲妥珠单抗的治疗改善了外周肿瘤控制和患者生存期，和曲妥珠单抗相对缺乏CNS活性。临床医生应该意识到这种关联。需要更好的治疗CNS复发。
Purpose: The aim of this study was to characterize the prevalence and predictors of central nervous system (CNS) metastasis among women with HER2-overexpressing metastatic breast cancer receiving trastuzumab-based therapy.Methods: The frequency and time course of isolated CNS progression were characterized among women with HER2-positive metastatic breast cancer, receiving chemotherapy with or without trastuzumab as first-line treatment for metastatic disease in two clinical trials. The first trial was a multicenter randomized phase III study of chemotherapy (doxorubicin/cyclophosphamide or paclitaxel) +/- trastuzumab, and the second was a multicenter phase II trial of vinorelbine + trastuzumab. All patients had measurable disease and were free of symptomatic CNS disease at initiation of study treatment.Results: Nearly 10% of patients receiving trastuzumab in combination with chemotherapy developed isolated CNS metastases as first site of tumor progression. Progression in the CNS tended to be a later event than progression at other sites among women receiving trastuzumab-based therapy. Trastuzumab-based treatment did not substantially delay onset of CNS metastases as initial site of progression. Following diagnosis with primary breast cancer, tumors with HER2 gene amplification tend to be associated with greater risk of isolated CNS progression compared with those lacking gene amplification.Conclusions: Patients with HER2-overexpressing metastatic breast cancer are at risk for isolated CNS progression, reflecting improved peripheral tumor control and patient survival through use of trastuzumab-based therapy, and a relative lack of CNS activity with trastuzumab. Clinicians should be aware of this association. Better treatments for CNS recurrences are needed.