- 作者：Bonnie Ky ; MD ; MSCE&lowast ; ; &dagger ; ; bonnie.ky@uphs.upenn.edu" class="auth_mail ; Mary Putt ; ScD&lowast ; ; &dagger ; ; Heloisa Sawaya ; MD ; PhD&Dagger ; ; Benjamin French ; PhD&lowast ; ; &dagger ; ; James L. Januzzi Jr. ; MD&Dagger ; ; Igal A. Sebag ; MD§ ; ; Juan Carlos Plana ; MD鈥?/sup> ; Victor Cohen ; MD¶ ; ; Jose Banchs ; MD# ; Joseph R. Carver ; MD&lowast ; ; Susan E. Wiegers ; MD&lowast ; &lowast ; ; Randolph P. Martin ; MD&dagger ; &dagger ; ; Michael H. Picard ; MD&Dagger ; ; Robert E. Gerszten ; MD&Dagger ; ; Elkan F. Halpern ; PhD&Dagger ; &Dagger ; ; Jonathan Passeri ; MD&Dagger ; ; Irene Kuter ; MD§ ; § ; ; Marielle Scherrer-Crosbie ; MD ; PhD&Dagger ; ; marielle@crosbie.com" class="auth_mail
- 关键词：cardio-oncology ; chemotherapy cardiotoxicity ; trastuzumab cardiotoxicity
- 刊名：Journal of the American College of Cardiology
- 出版年：4 March, 2014
- 年：2014
- 卷：63
- 期：8
- 页码：809-816
- 全文大小：546 K
Objectives
The aim of this study was to determine if individual or multiple biomarkers are associated with cardiotoxicity in聽patients with breast cancer undergoing cancer therapy.Background
Current methods to identify patients at risk for cardiotoxicity from cancer therapy are inadequate.
Methods
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.
Results
TnI, CRP, GDF-15, MPO, PlGF, and sFlt-1 levels increased from baseline to visit 2 (p聽< 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聽= 0.02) and MPO (HR: 1.34 per SD; 95% confidence interval: 1.00 to 1.80; p聽= 0.048) and in models combining both markers (p聽= 0.007 and p聽= 0.03, respectively). The risk of cardiotoxicity was 46.5% in patients with the largest changes in both markers (螖TnI >121.8 渭g/l; 螖MPO >422.6 pmol/l).
Conclusions
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.