Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab.
Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab.
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DOI：
10.1016/j.jacc.2013.10.061
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发表时间：
2014-03-04
影响因子：
24
通讯作者：
Scherrer-Crosbie, Marielle
中科院分区：
文献类型：
--
作者：
Ky, Bonnie;Putt, Mary;Sawaya, Heloisa;French, Benjamin;Januzzi, James L., Jr.;Sebag, Igal A.;Plana, Juan Carlos;Cohen, Victor;Banchs, Jose;Carver, Joseph R.;Wiegers, Susan E.;Martin, Randolph P.;Picard, Michael H.;Gerszten, Robert E.;Halpern, Elkan F.;Passeri, Jonathan;Kuter, Irene;Scherrer-Crosbie, Marielle
本研究的目的是确定个体或多种生物标志物是否与接受癌症治疗的乳腺癌患者的心脏毒性有关。目前识别癌症治疗中有心脏毒性风险的患者的方法是不充分的。我们在78名接受阿霉素和曲妥珠单抗治疗的乳腺癌患者的多中心队列中测量了8种生物标志物：超敏感肌钙蛋白I （TnI）、高敏c反应蛋白（CRP）、n端前b型利钠肽（NT-proBNP）、生长分化因子(GDF)-15、髓过氧化物酶（MPO）、胎盘生长因子（PlGF）、可溶性纤维样酪氨酸激酶受体(sFlt)-1和凝集素(gal)-3。心脏毒性，由心脏审查和评价委员会的标准定义，每3个月评估一次，长达15个月。在基线、第2次访问（3个月）以及第2次访问与基线之间的差异的函数中，评估每个生物标志物的心脏毒性风险风险风险比（hr）。评估关节模型中最有希望的生物标志物。TnI、CRP、GDF-15、MPO、PlGF和sFlt-1水平从基线到第2次就诊时升高（p < 0.05）。更大的心脏毒性风险与TnI （HR: 1.38 / SD； 95%可信区间：1.05 - 1.81;p = 0.02）和MPO （HR: 1.34 / SD； 95%可信区间：1.00 - 1.80;p = 0.048）以及合并这两种标志物的模型（p = 0.007和p = 0.03）的间隔变化有关。两项指标变化最大的患者发生心脏毒性的风险为46.5% （ΔTnI >121.8 μg/l； ΔMPO >422.6 pmol/l）。TnI和MPO水平的早期升高为接受阿霉素和曲妥珠单抗治疗的患者心脏毒性风险提供了附加信息。在应用于临床实践之前，有必要对这些发现进行独立验证。
The aim of this study was to determine if individual or multiple biomarkers are associated with cardiotoxicity in patients with breast cancer undergoing cancer therapy. Current methods to identify patients at risk for cardiotoxicity from cancer therapy are inadequate. We measured 8 biomarkers in a multicenter cohort of 78 patients with breast cancer undergoing doxorubicin and trastuzumab therapy: ultrasensitive troponin I (TnI), high-sensitivity C-reactive protein (CRP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt)-1, and galectin (gal)-3. Cardiotoxicity, defined by the Cardiac Review and Evaluation Committee criteria, was assessed every 3 months for up to 15 months. Hazard ratios (HRs) of cardiotoxicity risk were assessed for each biomarker at baseline, at visit 2 (3 months), and as a function of the difference between visit 2 and baseline. Joint models were assessed for the most promising biomarkers. TnI, CRP, GDF-15, MPO, PlGF, and sFlt-1 levels increased from baseline to visit 2 (p < 0.05). A greater risk of cardiotoxicity was associated with interval changes in TnI (HR: 1.38 per SD; 95% confidence interval: 1.05 to 1.81; p = 0.02) and MPO (HR: 1.34 per SD; 95% confidence interval: 1.00 to 1.80; p = 0.048) and in models combining both markers (p = 0.007 and p = 0.03, respectively). The risk of cardiotoxicity was 46.5% in patients with the largest changes in both markers (ΔTnI >121.8 μg/l; ΔMPO >422.6 pmol/l). Early increases in TnI and MPO levels offer additive information about the risk of cardiotoxicity in patients undergoing doxorubicin and trastuzumab therapy. Independent validation of these findings is necessary before application to clinical practice.
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影响因子：
11.5
作者：
Morris, Patrick G.;Chen, Carol;Dang, Chau T.
通讯作者：
Dang, Chau T.
影响因子：
37.8
作者：
Baldus, S;Heeschen, C;Hamm, CW
通讯作者：
Hamm, CW
影响因子：
45.3
作者：
Suter, Thomas M.;Procter, Marion;Piccart-Gebhart, Martine J.
通讯作者：
Piccart-Gebhart, Martine J.
影响因子：
24
作者：
Wilson Tang, W. H.;Tong, Wilson;Klein, Allan L.
通讯作者：
Klein, Allan L.
影响因子：
45.3
作者：
Seidman, A;Hudis, C;Keefe, D
通讯作者：
Keefe, D