Wadhwa Deepa, Fallah-Rad Nazanin, Grenier Debjani, Krahn Marianne, Fang Tielan, Ahmadie Roien, Walker Jonathan R, Lister Danica, Arora Rakesh C, Barac Ivan, Morris Andrew, Jassal Davinder S
Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Breast Cancer Res Treat. 2009 Sep;117(2):357-64. doi: 10.1007/s10549-008-0260-6. Epub 2008 Dec 10.
Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 +/- 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 +/- 5% vs. 51 +/- 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.
在临床试验之外，曲妥珠单抗介导的心脏毒性的发生率及管理尚未得到充分描述。目的和方法：本研究旨在回顾性评估接受辅助性曲妥珠单抗治疗的HER-2阳性乳腺癌患者群体中心脏功能障碍的发生率，描述其自然病史，并通过心脏磁共振成像确定其可逆程度。结果：在152例患者（平均年龄52±10岁）中，36例（24%）发生曲妥珠单抗介导的心肌病，大多数无症状。预测曲妥珠单抗介导的心脏功能障碍发生的因素包括既往高血压病史、吸烟史和冠状动脉疾病家族史。在曲妥珠单抗治疗的3个月内，正常队列与发生左心室收缩功能障碍的患者之间的左心室射血分数存在差异（61±5%对51±8%，P<0.01）。在6个月的随访期间，36例患者中的34例在心脏磁共振成像上显示左心室侧壁心外膜下线性延迟强化，提示曲妥珠单抗诱导的心肌炎。结论：约四分之一的女性在接受辅助性曲妥珠单抗治疗后可能发生左心室收缩功能障碍，因此需要谨慎选择患者并使用无创心脏成像进行密切的连续监测。
