Yu Anthony F, Moskowitz Chaya S, Chuy Katherine Lee, Yang Ji, Dang Chau T, Liu Jennifer E, Oeffinger Kevin C, Steingart Richard M
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Weill Cornell Medical College, New York, New York.
JACC CardioOncol. 2020 Jun;2(2):166-175. doi: 10.1016/j.jaccao.2020.03.002. Epub 2020 Jun 16.
Guidelines recommend left ventricular ejection fraction (LVEF) assessments every 3 months for cardiotoxicity monitoring during human epidermal growth factor receptor 2 (HER2) targeted therapy. Evidence in support of this practice is lacking.
This study examines the association between adherence to cardiotoxicity surveillance guidelines and heart failure (HF) in HER2-positive breast cancer patients.
A case-control study was performed in 53 patients who developed cardiotoxicity during HER2 targeted therapy, and 159 controls matched by age, anthracycline exposure, and year of treatment. Cardiotoxicity was defined as HF (New York Heart Association functional class III or IV) or cardiac death. Adherence to cardiotoxicity surveillance guidelines was ascertained from the beginning of HER2 targeted therapy to the diagnosis date of HF for cases or the corresponding timepoint for matched controls. Conditional logistic regression was used for case-control comparisons.
Eighty-one percent of cases and controls were previously treated with an anthracycline. Adherence to cardiotoxicity surveillance guidelines during the entire observation period or during the first 6 months of treatment was not associated with lower risk of HF. An LVEF <55% at any surveillance timepoint was identified in 49% of cases and 3% of controls, and an LVEF <55% during the final surveillance timepoint before developing HF was identified in 54% of cases and 4% of controls. In multivariable-adjusted analyses, LVEF <55% at any timepoint or during the final surveillance timepoint (odds ratio: 27.0; 95% confidence interval: 9.3 to 78.8 and odds ratio: 25.6; 95% confidence interval: 7.3 to 90.3, respectively) was associated with HF.
Patients with LVEF <55% on routine surveillance during HER2 targeted therapy are at increased risk for HF. Additional studies to define their optimal management are warranted.
指南建议在人表皮生长因子受体2(HER2)靶向治疗期间,每3个月进行一次左心室射血分数(LVEF)评估,以监测心脏毒性。但缺乏支持这一做法的证据。
本研究探讨HER2阳性乳腺癌患者遵守心脏毒性监测指南与心力衰竭(HF)之间的关联。
对53例在HER2靶向治疗期间发生心脏毒性的患者和159例按年龄、蒽环类药物暴露情况和治疗年份匹配的对照进行了一项病例对照研究。心脏毒性定义为心力衰竭(纽约心脏协会功能分级III或IV级)或心源性死亡。从HER2靶向治疗开始至病例发生心力衰竭的诊断日期或匹配对照的相应时间点,确定对心脏毒性监测指南的遵守情况。采用条件逻辑回归进行病例对照比较。
81%的病例和对照曾接受过蒽环类药物治疗。在整个观察期或治疗的前6个月内遵守心脏毒性监测指南与较低的心力衰竭风险无关。在49%的病例和3%的对照中,在任何监测时间点LVEF<55%,在发生心力衰竭前的最后监测时间点,54%的病例和4%的对照LVEF<55%。在多变量调整分析中,在任何时间点或最后监测时间点LVEF<55%(比值比:27.0;95%置信区间:9.3至78.8;比值比:25.6;95%置信区间:7.3至90.3)与心力衰竭相关。
在HER2靶向治疗期间常规监测中LVEF<55%的患者发生心力衰竭的风险增加。有必要进行更多研究以确定其最佳管理方法。