HER2陽性轉移乳癌之標靶藥物回顧

Review of Targeted Therapy for HER2-Positive Metastatic Breast Cancer

在過去，人類表皮生長因子受體2（HER2）陽性的乳癌被視為預後不佳的指標，但因近十五年來，對HER2分子的了解及藥物的進步，徹底改變此族群的治療與預後。Trastuzumab賀癌平是第一個被核准的標靶藥物。爾後出現lapatinib泰嘉錠，適當併用其他治療，可增加疾病存活率。近年來陸續通過pertuzumab賀疾妥與ado-trantuzumab emtansine賀癌寧，針對賀癌平的抗藥性作突破性的改變。本文針對HER2陽性之轉移性乳癌，介紹HER2家族四個標靶藥物的演進及重要的臨床試驗，如何適當搭配標靶藥物，賀爾蒙藥物，及化學治療藥物，達到最佳療效與最低副作用，期待未來轉移性乳癌，能有更少的抗藥性與更好的治療效果。

The incidence of breast cancer is rapidly increasing but the mortality rate has not increased proportionally in the past fifteen years. The monoclonal antibodies of human epidermal growth factor receptor 2 (HER2) has revolutionized HER2-positive metastatic breast cancer treatment and prognosis. Trastuzumab, the first anti-HER2 targeted therapy approved by the U.S. Food and Drug Administration, has changed the grave prognosis of HER2-positive breast cancer. In addition, lapatinib is a small molecule dual reversible tyrosine kinase inhibitor targeting HER2 and HER1. When lapatinib is combined with either capecitabine or letrozole, the survival of HER2 overexpressing metastatic breast cancer patients with either brain metastases or postmenopausal status is improved. In recent years, new targeted agents, pertuzumab and ado-trantuzumab emtansine, were approved for HER2 overexpressing breast cancer. In this paper, we reviewed the mechanism and evolution of HER2 targeting agents. An adequate combination of these agents with chemotherapy would result in the improvement of overall survival and quality of life in metastatic HER2-positive breast cancer patients.