CNS metastases in breast cancer: old challenge, new frontiers.
CNS metastases in breast cancer: old challenge, new frontiers.
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DOI：
10.1158/1078-0432.ccr-13-0790
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发表时间：
2013-12-01
期刊：
影响因子：
--
通讯作者：
Steeg PS
中科院分区：
文献类型：
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作者：
Lin NU;Amiri-Kordestani L;Palmieri D;Liewehr DJ;Steeg PS
尽管乳腺癌患者的治疗取得了重大进展，但中枢神经系统(CNS)转移仍然是一个棘手的问题，特别是在转移性HER2阳性和三阴性乳腺癌患者中。随着治疗颅外疾病的系统疗法的改善，一些患者的生存时间更长，中枢神经系统受累的频率似乎也在增加。此外，在早期阶段，中枢神经系统仍然是复发的潜在避难所。本文重点介绍了临床前生物学相关模型的研究进展，包括亲脑细胞系的建立和药物防治脑转移的研究进展，并总结了我们目前对中枢神经系统复发生物学的认识。从临床的角度，讨论了各种治疗方法，包括改善药物输送的方法，新型细胞毒剂和靶向治疗。回顾了当前试验设计和终点中的挑战。最后，我们讨论了有前景的新方向，包括新的试验设计，相关的成像技术，以及增强的翻译机会。
Despite major therapeutic advances in the management of patients with breast cancer, central nervous system (CNS) metastases remain an intractable problem, particularly in patients with metastatic HER2 positive and triple-negative breast cancer. As systemic therapies to treat extracranial disease improve, some patients are surviving longer, and the frequency of CNS involvement appears to be increasing. Furthermore, in the early-stage setting, the CNS remains a potential sanctuary site for relapse. This Review highlights advances in the development of biologically relevant preclinical models including the development of brain-tropic cell lines for testing of agents to prevent and treat brain metastases, and summarizes our current understanding of the biology of CNS relapse. From a clinical perspective, a variety of therapeutic approaches are discussed, including methods to improve drug delivery, novel cytotoxic agents, and targeted therapies. Challenges in current trial design and endpoints are reviewed. Finally, we discuss promising new directions, including novel trial designs, correlative imaging techniques, and enhanced translational opportunities.