Department of Breast Cancer and Reconstructive Surgery, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland.
Ann Oncol. 2010 May;21(5):917-24. doi: 10.1093/annonc/mdp353. Epub 2009 Aug 28.
Patients with metastatic central nervous system (mCNS) disease progression from breast cancer have a poor prognosis and often develop associated neurological complications. Human epidermal growth factor receptor 2 (HER2)-positivity status increases the risk of developing mCNS disease. Trastuzumab is an mAb that targets HER2 and is known to extend survival across all stages of HER2-positive breast cancer.
This review considers evidence from preclinical and clinical studies examining the value of continuing trastuzumab treatment in patients who develop mCNS disease. A wealth of data from clinical studies showed that trastuzumab prolonged survival in patients with mCNS disease, compared with no trastuzumab treatment, by effectively controlling their non-CNS disease. Trastuzumab has also been shown to penetrate an impaired blood-brain barrier to a limited degree, such as during radiotherapy, and intrathecal delivery of trastuzumab to the central nervous system (CNS) has shown promise. Research efforts are focussing on improving the delivery of trastuzumab to the CNS.
Evidence indicates that patients with mCNS disease from HER2-positive breast cancer should continue to receive trastuzumab to control HER2-positive metastases outside the CNS and receive established therapies to control the mCNS disease.
患有转移性中枢神经系统(mCNS)疾病的乳腺癌患者预后较差,常伴有相关的神经并发症。人表皮生长因子受体 2(HER2)阳性状态增加了发生 mCNS 疾病的风险。曲妥珠单抗是一种针对 HER2 的 mAb,已知可延长所有 HER2 阳性乳腺癌阶段的生存期。
本综述考虑了来自临床前和临床研究的证据,这些研究检查了继续曲妥珠单抗治疗在发生 mCNS 疾病的患者中的价值。大量的临床研究数据表明,与未接受曲妥珠单抗治疗相比,曲妥珠单抗通过有效控制非 CNS 疾病,延长了 mCNS 疾病患者的生存期。曲妥珠单抗还被证明可以穿透受损的血脑屏障,程度有限,例如在放疗期间,并且向中枢神经系统(CNS)中给予曲妥珠单抗显示出有希望。研究工作的重点是改善曲妥珠单抗向 CNS 的递送。
有证据表明,HER2 阳性乳腺癌患者发生 mCNS 疾病后,应继续接受曲妥珠单抗治疗,以控制 CNS 外的 HER2 阳性转移,并接受既定疗法控制 mCNS 疾病。