Department of Medicine and Breast Cancer Research Program, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Ther Adv Med Oncol. 2012 May;4(3):139-47. doi: 10.1177/1758834012440834.
In recent years, new strategies for the treatment of breast cancer have focused on extensive target identification and understanding the expression, regulation and function of critical signaling pathways involved in breast cancer initiation and progression. This has led to significant progress in developing and understanding human epidermal growth factor receptor 2 (HER2)-targeted therapies, which in turn, has translated into significant increases in median survival for patients with HER2-overexpressing breast cancer. It is becoming increasingly difficult to make specific recommendations for the optimal treatment of HER2-overexpressing breast cancer since the field is evolving so rapidly. However, despite the many randomized trials that have been undertaken showing improvement in survival, the current standard treatment for HER2-overexpressing breast cancer continues to revolve around the addition of chemotherapy to a HER2-targeted agent, which in turn, carries substantial toxicities. This article reviews agents that have recently been investigated to treat HER2-overexpressing breast cancers. The goal is ultimately to increase the magnitude and duration of response to trastuzumab-based treatment while minimizing toxicity. Studies addressing length of therapy duration, the superiority and side-effect profile of the different biological drug combinations, and determination of biomarkers of resistance to HER2 therapy will be instrumental in decreasing morbidity and mortality for patients with HER2-overexpressing breast cancer.
近年来，乳腺癌治疗的新策略侧重于广泛的目标识别，并深入了解参与乳腺癌发生和发展的关键信号通路的表达、调节和功能。这导致了在开发和理解人表皮生长因子受体 2（HER2）靶向治疗方面取得了重大进展，进而使 HER2 过表达乳腺癌患者的中位生存期显著延长。由于该领域发展迅速，很难为 HER2 过表达乳腺癌的最佳治疗提出具体建议。然而，尽管进行了许多随机试验表明生存得到了改善，但 HER2 过表达乳腺癌的当前标准治疗方法仍然是在 HER2 靶向药物的基础上添加化疗，这反过来又会带来严重的毒性。本文综述了最近用于治疗 HER2 过表达乳腺癌的药物。其最终目标是在最小化毒性的同时，增加基于曲妥珠单抗治疗的反应幅度和持续时间。研究解决治疗持续时间、不同生物药物组合的优越性和副作用特征以及确定对 HER2 治疗的耐药性生物标志物，将有助于降低 HER2 过表达乳腺癌患者的发病率和死亡率。
