在乳腺癌患者接受蒽环类药物治疗期间的神经激素阻断和循环心血管生物标志物：来自 PRADA（蒽环类药物辅助乳腺癌治疗期间预防心功能障碍）研究的结果。
Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study.
机构信息
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
Center for Heart Failure Research, University of Oslo, Norway.
出版信息
J Am Heart Assoc. 2017 Nov 8;6(11):e006513. doi: 10.1161/JAHA.117.006513.
BACKGROUND
Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.
METHODS AND RESULTS
This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and galectin-3 increased during anthracycline therapy (all <0.05). The troponin response was attenuated by metoprolol (<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy.
CONCLUSIONS
Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.
背景
蒽环类药物与心脏毒性作用有关。心血管生物标志物可反映心肌损伤、功能障碍、炎症和纤维化，并且可能先于并预测左心室损伤的发生。本研究的目的是评估：（1）循环心血管生物标志物的纵向变化，（2）琥珀酸美托洛尔和坎地沙坦西酯对生物标志物反应的影响，以及（3）接受蒽环类药物治疗的早期乳腺癌患者治疗中生物标志物浓度变化与随后左心室功能障碍之间的相关性。
方法和结果
本报告涵盖了 PRADA（辅助乳腺癌治疗期间预防心脏功能障碍）试验中的 121 名女性，该试验为 2×2 析因、安慰剂对照、双盲试验，同时给予美托洛尔和坎地沙坦，与包含蒽环类药物表柔比星（总累积剂量 240-400mg/m）的抗癌治疗同时使用。在接受蒽环类药物治疗前后，进行了心血管磁共振成像、超声心动图图像和循环生物标志物水平的检测。在蒽环类药物治疗期间，心脏肌钙蛋白 I 和 T、B 型利钠肽、N 端 B 型利钠肽前体、C 反应蛋白和半乳糖凝集素-3 升高（均<0.05）。美托洛尔（<0.05）可减轻心肌肌钙蛋白的反应，但坎地沙坦无此作用。生物标志物浓度的变化与蒽环类药物治疗期间心脏功能的变化之间没有关联。
结论
用现代蒽环类药物剂量治疗早期乳腺癌与循环心血管生物标志物的增加有关。然而，这种增加与心室功能的早期下降无关。β受体阻滞剂可能减轻早期心肌损伤，但这种减轻是否能转化为长期减少发生心室功能障碍的风险尚不清楚。
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