Cardiotoxicity Associated with Trastuzumab Therapy in Taiwan: A Single Medical Center's 5-Year Experience

乳癌治療用藥賀癌平（Trastuzumab）之心臟毒性：單一醫學中心之五年臨床經驗

張哲明(Che-Ming Chang) ； 鄭翠芬(Fiona Tsui-Fen Cheng) ； 楊圳隆(Tsen-Long Yang) ； 溫武慶(Wu-Chin Wen)

《台灣癌症醫學雜誌》 2卷2期 (2015/06) Pp. 139-150

https://doi.org/10.6323/JCRP.2015.2.2.05

摘要

目的：本研究是研究乳癌病患在賀癌平（Trastuzumab）治療後之心臟功能及心臟大小之早期改變。材料和方法：研究73位人類表皮生長因子受體2（HER2）過度表現之乳癌女性病患在賀癌平治療前後之心臟超音波變化；研究期間於西元2007年10月起至2013年9月；心血管危險因子之分析包括年齡、身體質量比（BMI）、抽煙與否、有無高血壓、生活型態、有無乳癌家族史、有無高血脂、有無糖尿病、有無憂鬱、有無使用血管轉換抑制劑或血管張力素受體阻斷劑或乙型阻斷劑之使用。結果：心臟相關之併發症發生於14位病患（19.2%），包括無症狀之左心室收縮異常（n=12），有症狀之心臟衰竭（n=2），新發生無症狀之左束支傳導阻滯（n=1），心電圖上新發生之負T波變化（n=2），心包膜積水（n=1），和死亡（n=1）。而心臟舒張功能及右心室大小功能並無明顯變化。大部份乳癌病患經賀癌平治療後維持在無症狀之心臟功能狀態。明顯之左心室收縮功能下降發生於14位病患（19.2%），和三個月後明顯的二尖瓣逆流（≥grade1）發生於9位病患（9.6%）。結論：賀癌平之使用可能會導致左心室收縮功能下降（但僅2.7%會產生有症狀的心臟衰竭）和明顯的二尖瓣逆流，故在治療期間定期心臟超音波監測是必要的。

關鍵字

賀癌平 ； 相關之心臟毒性 ； 乳癌 ； 人類表皮生長因子受體2

並列摘要

Introduction: Trastuzumab, a recombinant humanized monoclonal antibody, targets the external domain of HER2 to improve the efficacy of HER2-positive breast cancer treatment and inhibit carcinoma cellular proliferation. The purpose of this study was to identify early changes in cardiac function and dimensional changes in heart size in patients treated with trastuzumab. Materials and Methods: Seventy three female patients with Her2/neu overexpression (IHC 3+/Fish +) in breast cancer underwent echocardiography before and after trastuzumab therapy. Results: Cardiac complications developed in 14 patients (19.2%), including asymptomatic left ventricle systolic dysfunction (n=12), symptomatic heart failure (n=2), new asymptomatic left bundle branch block (n=1), new negative T waves on electrocardiogram (n=2), pericardial effusion (n=1), and death (n=1). No significant deterioration in diastolic function was noted, and right heart diameters and function did not change significantly. Most patients remained in an asymptomatic stage of cardiac disease. A significant decrease in left ventricular ejection fraction (LVEF) was observed in 14 patients (19.2%), and new mitral regurgitation (≥ grade 1) was noted after 3 months of trastuzumab therapy in 7 patients (9.6%). Conclusions: Trastuzumab led to measurable decreases in LVEF (but only 2.7% was symptomatic heart failure) and new mitral regurgitation. Therefore, regular follow-up with echocardiography is essential for early detection and prevention of trastuzumab-induced cardiomyopathy.

並列關鍵字

trastuzumab ； cardiotoxicity ； breast cancer ； HER2 over expression