Yuan Peng, Gao Song-Lin
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Chronic Dis Transl Med. 2017 Mar 8;3(1):21-32. doi: 10.1016/j.cdtm.2017.01.004. eCollection 2017 Mar 25.
After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications. Postoperative or preoperative radiation is usually delivered in conjunction with surgical resection to boost local control. Adjuvant whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its impairment of neurocognitive function while having no benefit for OS. Although WBRT is still the standard treatment for local control of diffuse BM, SRS is a promising treatment for diffuse BM as the technique continues to improve. Although large molecules have difficulty crossing the blood brain barrier, trastuzumab-containing regimens are critical for treating HER2-positive BCBM patients because they significantly prolong OS. Tyrosine kinase inhibitors are more capable of crossing into the brain and they have been shown to be beneficial for treating BM in HER2-positive patients, especially lapatinib combined with capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2-positive BCBM scenario as well. In this review, we also discuss several strategies for delivering drugs into the central nervous system and several microRNAs that have the potential to become biomarkers of BCBM.
引入曲妥珠单抗（一种与人表皮生长因子受体2（HER2）结合的单克隆抗体）后，HER2阳性乳腺癌患者的总生存期（OS）有了显著改善。然而，在这些患者中，脑转移（BM）的发生率一直在上升，且死于颅内进展的患者比例增加，这使得HER2阳性乳腺癌脑转移（BCBM）成为一个备受关注的关键问题。对于局限性BM的局部控制，立体定向放射外科（SRS）和手术切除是具有不同临床适应证的可用方式。手术切除通常联合术后或术前放疗以增强局部控制。对于局限性BM，应推迟辅助性全脑放疗（WBRT），因为其会损害神经认知功能，同时对OS无益处。虽然WBRT仍是弥漫性BM局部控制的标准治疗方法，但随着技术不断改进，SRS是弥漫性BM的一种有前景的治疗方法。尽管大分子难以穿过血脑屏障，但含曲妥珠单抗的方案对于治疗HER2阳性BCBM患者至关重要，因为它们能显著延长OS。酪氨酸激酶抑制剂更易进入大脑，且已证明其对治疗HER2阳性患者的BM有益，尤其是拉帕替尼联合卡培他滨。抗血管生成药物贝伐单抗也可应用于HER2阳性BCBM的情况。在本综述中，我们还讨论了几种将药物递送至中枢神经系统的策略以及几种有可能成为BCBM生物标志物的微小RNA。
