Division of Medical Oncology, Santa Maria della Misericordia Azienda Ospedaliera di Perugia via Dottori, Perugia, Italy.
Curr Cancer Drug Targets. 2012 Mar;12(3):210-7. doi: 10.2174/156800912799277548.
Central nervous system (CNS) metastases from breast cancer (BC) represent an important cause of disease-related morbidity and mortality. For BC patients who develop CNS metastases, local control measures (both surgery and radiation) are essentially palliative and usually poorly effective, with systemic therapies often failing to achieve optimal control mainly due to the presence of the blood-brain barrier which hampers adequate penetration of therapeutic agents into the brain. However, recent evidence suggests that the status of the human epidermal growth factor receptor-2 (HER2) strongly influences the incidence of CNS metastases and the survival of BC patients from the time of development of CNS metastases, with HER2-positive (HER2+) patients generally experiencing higher rates of CNS metastases and prolonged overall survival compared to patients with HER2-negative disease. This phenomenon likely reflects the difficult CNS drug-penetration and improved control of extra-CNS disease following the clinical use of the anti-HER2 monoclonal antibody trastuzumab. Importantly, this HER2-based survival difference has important implications when planning the optimal treatment of BC patients with CNS metastases. To date, although no systemic therapy has been specifically approved for the treatment of CNS metastases from BC, several targeted agents are being clinically developed for this purpose. In the present review we will discuss the targeted therapies that are under investigation for the treatment of CNS metastases from BC, highlighting the different implications based on whether a given agent is being developed to target CNS metastases from HER2+ or HER2-negative breast cancer.
乳腺癌（BC）中枢神经系统（CNS）转移是导致疾病相关发病率和死亡率的重要原因。对于发生 CNS 转移的 BC 患者，局部控制措施（手术和放疗）本质上是姑息性的，通常效果不佳，全身治疗往往无法达到最佳控制，主要是由于血脑屏障的存在阻碍了治疗药物充分进入大脑。然而，最近的证据表明，人类表皮生长因子受体 2（HER2）的状态强烈影响 CNS 转移的发生以及发生 CNS 转移后 BC 患者的生存，HER2 阳性（HER2+）患者通常比 HER2 阴性疾病患者经历更高的 CNS 转移率和更长的总生存期。这种现象可能反映了抗 HER2 单克隆抗体曲妥珠单抗的临床应用后，CNS 药物渗透困难和对 CNS 外疾病控制的改善。重要的是，在为 CNS 转移的 BC 患者制定最佳治疗方案时，这种基于 HER2 的生存差异具有重要意义。迄今为止，尽管尚无专门批准用于治疗 BC 中枢神经系统转移的全身性治疗方法，但已有几种靶向药物正在为此目的进行临床开发。在本综述中，我们将讨论正在研究用于治疗 BC 中枢神经系统转移的靶向治疗方法，重点根据特定药物是针对 HER2+还是 HER2-乳腺癌的 CNS 转移进行开发来突出不同的意义。
