激素受体阳性乳腺癌脑转移药物治疗研究进展

Advances in the treatment of hormone receptor-positive metastatic breast cancer with brain metastases

目的乳腺癌是仅次于肺癌最易发生脑转移的原发肿瘤。激素受体阳性乳腺癌是转移性乳腺癌的主体,脑转移是该类患者的主要死亡原因,但目前对于激素受体阳性乳腺癌脑转移(breast cancer brain metastases,BCBM)的有效治疗报道较少。本研究旨探讨激素受体阳性BCBM药物治疗的相关研究进展。方法应用PubMed及CNKI期刊全文数据库检索系统,以"乳腺癌、脑转移和激素受体阳性乳腺癌"等为关键词,检索2005-01-2016-06相关文献,共检测到中文文献128条,英文文献55条。纳入标准:1)BCBM的危险因素及其预后;2)BCBM的当前治疗选择;3)激素受体阳性BCBM药物治疗。根据纳入标准,符合分析的文献25篇。结果限制BCBM药物治疗进展的主要原因是血脑屏障的存在。激素在BCBM治疗中的疗效尚不明确,但有大量个案报道他莫昔芬等内分泌药物对BCBM治疗有效。非对照试验表明某些细胞毒类药物,如卡培他滨、替莫唑胺(temozolomide,TMZ)和卡莫司汀晶片植入剂,对激素受体阳性BCBM有效,但没有足够证据支持具体的治疗方案。免疫抑制剂abemaciclib在激素受体阳性BCBM患者中的应用正处于Ⅱ期临床试验阶段。虽然高分子药物难以通过完整的血脑屏障,但研究证实部分单克隆抗体,如曲妥珠单抗和贝伐单抗,对BCBM治疗有效。纳米药物传递系统能提高中枢神经系统药物转移,有较好发展前景。由纳米颗粒包裹的多柔比星和etirinotecan pegol对治疗激素受体阳性BCBM有一定的疗效。结论尽管目前没有专门批准用于激素受体阳性BCBM系统治疗的药物,但有大量的临床试验正在进行中,将为临床治疗带来启示。

OBJECTIVE Breast cancer is second to lung cancer as the leading cause of brain metastasis.Brain metastases are a major cause of mortality for patients with hormone receptor-positive breast cancer,yet little is known about the optimal treatment of brain disease in these patients.This article aims to review the advances in the medicine treatment of hormone receptor-positive breast cancer with brain metastases.METHODS We retrieved the articles from January2005 to June 2016 by PubMed and CNKI full-text database retrieval system with ＂breast cancer,brain metastases and hormone receptor-positive breast cancer＂as key words,A total of 128 articles in Chinese and 55 articles in English were retrieved.The inclusion criteria were listed as follows：（1）The risk and prognosis of breast cancer brain metastasis;（2）Current treatment options for breast cancer brain metastasis;（3）Systemic therapy of hormone receptor-positive metastatic breast cancer with brain metastases.34 articles were finally selected according to the inclusion criteria.RESULTS Blood-brain barrier is a major limitation to the development of systemic treatments for breast cancer brain metastasis.The effects of hormone therapy specifically on brain metastases are unclear,however,a number of case reports documented responses in the brain for tamoxifen and other hormone therapies.Uncontrolled studies suggest that some cytotoxic drugs such as capecitabine,temozolomide and carmustine have activity in the brain,but the evidence is insufficient to support specific regimens for this indication.The immunosuppressive agent abemaciclib is currently being evaluated in phaseⅡtrial for patients with brain metastases from hormone receptor-positive breast cancer.Despite the fact that high molecular weight drugs generally cannot cross an intact blood-brain barrier,evidence suggests that some monoclonal antibodies like trastuzumab and bevacizumab are effective for breast cancer brain metastases.Nanoparticle delivery systems are another promising approach to enhancing central nervous system drug delivery.Nanoparticle-based cytotoxic such as doxorubicin and etirinotecan pegol have potential for the treatment of breast cancer brain metastases.CONCLUSION Although there are currently no systemic therapies specifically approved for the treatment of breast cancer brain metastases,there are a number of promising clinical trials underway.