Mahtani Reshma, Hineman Lisa
Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, and Los Angeles Cancer Network, Los Angeles, California.
J Adv Pract Oncol. 2019 Mar;10(2):136-153. Epub 2019 Mar 1.
Although breast cancer is a heterogeneous disease, approximately 20% to 25% of patients diagnosed with breast cancer have amplification of the HER2 gene. The FDA approval of trastuzumab for the treatment of HER2-positive (HER2+) metastatic breast cancer in 1998 represented a major breakthrough for patients with HER2+ disease. In 2006, the FDA extended its approval for use in the adjuvant setting. In recent years, trials have been conducted to identify the appropriate duration of therapy in combination with chemotherapy. More recently, trials incorporating newer HER2-targeted therapies have been conducted. Some trials have demonstrated the importance of considering neoadjuvant HER2-directed therapies for selected patients with HER2+ disease, highlighting the fact that achieving pathologic complete response has important prognostic implications. In order to continue treatment and optimize patient safety, the effective and timely management of treatment-related adverse events (AEs) is crucial. As they are on the front lines of patient care, advanced practitioners need to be able to assess the clinical implications of recent advances and integrate them into practice. One area of unmet need in the management of metastatic HER2-positive disease is the treatment of brain metastases, with several promising therapies under investigation. Using several case studies as a foundation, this article highlights current and emerging data on HER2-directed therapies, outlines strategies for managing AEs, and reviews the key issues surrounding brain metastases and associated novel therapies under investigation.
尽管乳腺癌是一种异质性疾病，但在确诊为乳腺癌的患者中，约20%至25%存在HER2基因扩增。1998年美国食品药品监督管理局（FDA）批准曲妥珠单抗用于治疗HER2阳性（HER2+）转移性乳腺癌，这对HER2+疾病患者而言是一项重大突破。2006年，FDA扩大了其在辅助治疗中的应用批准。近年来，已开展试验以确定联合化疗的适当治疗持续时间。最近，还开展了纳入更新的HER2靶向治疗的试验。一些试验证明了对于部分HER2+疾病患者考虑新辅助HER2导向治疗的重要性，突出了实现病理完全缓解具有重要预后意义这一事实。为了继续治疗并优化患者安全性，有效且及时地管理治疗相关不良事件（AE）至关重要。由于高级从业者处于患者护理的前沿，他们需要能够评估近期进展的临床意义并将其融入实践。转移性HER2阳性疾病管理中一个未满足需求的领域是脑转移瘤的治疗，目前有几种有前景的疗法正在研究中。本文以几个病例研究为基础，重点介绍了HER2导向治疗的当前和新出现的数据，概述了管理AE的策略，并回顾了围绕脑转移瘤及相关正在研究的新型疗法的关键问题。
