Military Institute of Medicine, Department of Oncology, Warsaw, Poland.
German Breast Group, Neu-Isenburg, Germany; Sana-Klinikum Offenbach, Germany.
Cancer Treat Rev. 2018 Jun;67:71-77. doi: 10.1016/j.ctrv.2018.05.004. Epub 2018 May 9.
Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients.
约 30-50%的晚期 HER2 阳性乳腺癌患者会发生中枢神经系统（CNS）转移，年风险约为 10%，其中一半患者会死于脑转移。接受根治性治疗的早期 HER2 阳性乳腺癌患者也存在发生脑转移的风险增加。HER2 阳性乳腺癌患者的脑转移通常构成复发的第一个部位。抗 HER2 单克隆抗体曲妥珠单抗和帕妥珠单抗的应用显著延迟了有症状脑疾病的发生：然而，这些化合物向中枢神经系统的有限渗透限制了它们的疗效。表皮生长因子受体家族的小分子酪氨酸激酶抑制剂在晚期和新辅助治疗 HER2 阳性乳腺癌中均具有活性。这些化合物良好的理化性质允许它们更有效地穿透血脑屏障，并为更有效地预防和治疗脑转移提供了希望。本文综述了目前可用或正在研究的 HER2 酪氨酸激酶抑制剂：拉帕替尼、奈拉替尼、阿法替尼和图卡替尼在治疗 HER2 阳性乳腺癌患者脑转移中的作用。
