Martin Miguel, López-Tarruella Sara
From the Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain.
Am Soc Clin Oncol Educ Book. 2016;35:e64-70. doi: 10.1200/EDBK_159167.
The natural history of HER2-positive breast cancer has progressively improved since the introduction of the first anti-HER2 directed therapy (trastuzumab). Trastuzumab has significantly increased survival of patients with HER2-positive metastatic breast cancer and, after the standardization of the use of this drug in the adjuvant setting in 2005, has also avoided many disease recurrences and, consequently, saved many lives. Later on, the introduction of lapatinib offered new choices for patients with advanced HER2-positive breast cancer, although the drug has failed to show a clear efficacy in the adjuvant setting. New promising drugs have been approved to broaden the horizon of HER2-positive breast cancer such as pertuzumab or T-DM1, but we need new options to further improve the management of these diseases. In this review, we cover new strategies that are currently under evaluation for the treatment of patients with HER2-positive breast cancer, including new tyrosine kinase inhibitors (neratinib, ONT-380), new antibody-drug conjugates targeting HER2 (MM-302), and new indications of already approved drugs (T-DM1), as well as the potential dual combinations of anti-HER2 therapy with phosphoinositide 3-kinase/mTOR or cell cycle inhibitors (palbociclib, abemaciclib). Last but not least, we briefly review a new paradigm of emerging approaches that involve the host immune response, HER2 breast cancer vaccines, and other immune strategies, including immune checkpoint inhibition.
自首个抗HER2定向治疗药物（曲妥珠单抗）问世以来，HER2阳性乳腺癌的自然病程已逐步改善。曲妥珠单抗显著提高了HER2阳性转移性乳腺癌患者的生存率，并且在2005年该药物在辅助治疗中的使用标准化后，还避免了许多疾病复发，从而挽救了许多生命。后来，拉帕替尼的引入为晚期HER2阳性乳腺癌患者提供了新的选择，尽管该药物在辅助治疗中未能显示出明确的疗效。新的有前景的药物如帕妥珠单抗或曲妥珠单抗偶联物（T-DM1）已获批准，拓宽了HER2阳性乳腺癌的治疗前景，但我们需要新的选择来进一步改善这些疾病的治疗。在本综述中，我们涵盖了目前正在评估的用于治疗HER2阳性乳腺癌患者的新策略，包括新型酪氨酸激酶抑制剂（来那替尼、ONT-380）、靶向HER2的新型抗体药物偶联物（MM-302）、已批准药物的新适应证（T-DM1），以及抗HER2治疗与磷酸肌醇3激酶/哺乳动物雷帕霉素靶蛋白或细胞周期抑制剂（帕博西尼、阿贝西利）的潜在联合应用。最后但同样重要的是，我们简要回顾了一种新出现的方法范式，涉及宿主免疫反应、HER2乳腺癌疫苗和其他免疫策略，包括免疫检查点抑制。
