Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation
Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation
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DOI：
10.1200/jco.2009.27.3615
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发表时间：
2010-09-01
影响因子：
45.3
通讯作者：
Cipolla, Carlo M.
中科院分区：
文献类型：
--
作者：
Cardinale, Daniela;Colombo, Alessandro;Cipolla, Carlo M.
目的用曲妥珠单抗治疗乳腺癌时，高达 34% 的患者会出现心脏毒性。在大多数患者中，曲妥珠单抗引起的心脏毒性 (TIC) 是可逆的：曲妥珠单抗停药后以及或有时不开始心力衰竭 (HF) 治疗后，左心室射血分数 (LVEF) 有所改善。然而，TIC 的可逆性是不可预见的，识别处于危险中的患者和无法从心功能障碍中恢复的患者至关重要。肌钙蛋白 I (TNI) 在识别 TIC 风险患者和预测 LVEF 恢复方面的作用从未被研究过。 患者和方法 总共有 251 名女性参与其中。在每个曲妥珠单抗周期之前和之后测量 TNI。在基线、曲妥珠单抗治疗期间每 3 个月以及之后每 6 个月评估 LVEF。如果出现 TIC，则停用曲妥珠单抗，并开始使用依那普利和卡维地洛进行心力衰竭治疗。 TIC 定义为 LVEF 降低 > 10 个单位且低于 50%。 TIC 恢复定义为 LVEF 增加超过 50%。结果 42 名患者 (17%) 发生 TIC，并且在 TNI 升高的患者中更为常见 (TNI +；62% vs 5%；P < .001)。 25 名患者 (60%) 从 TIC 中康复。 TNI + 患者中 LVEF 恢复的频率较低（35% vs 100%；P < .001）。在多变量分析中，TNI + 是 TIC 的唯一独立预测因子（风险比 [HR]，22.9；95% CI，11.6 至 45.5；P < .001）和 LVEF 恢复不足（HR，2.88；95% CI，1.78 至 4.65；P < .001）。 结论 TNI + 确定接受曲妥珠单抗治疗的患者存在心脏毒性的风险，并且尽管进行心力衰竭治疗也不太可能从心功能障碍中恢复。
PurposeTreatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated.Patients and MethodsIn total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%.ResultsTIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI +; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI + patients (35% v 100%; P < .001). At multivariate analysis, TNI + was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI, 1.78 to 4.65; P < .001).ConclusionTNI + identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.