Troponin I and C-Reactive Protein Are Commonly Detected in Patients with Breast Cancer Treated with Dose-Dense Chemotherapy Incorporating Trastuzumab and Lapatinib
Open Access
- 15 May 2011
- journal article
- clinical trial
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 17 (10), 3490-3499
- https://doi.org/10.1158/1078-0432.ccr-10-1359
Abstract
Purpose: There are no validated methods of early detection of cardiotoxicity from trastuzumab (T) following anthracycline-based chemotherapy. Currently changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Within a prospective feasibility study of dose-dense (dd) doxorubicin and cyclophosphamide (AC) → weekly paclitaxel (P) with T and lapatinib (L), we included a preplanned analysis of correlative cardiac Troponin I (cTnI) and C-reactive protein (CRP) as early biomarkers of cardiotoxicity. Experimental Design: As previously described, patients received ddACx 4→PTL→TL. LVEF was assessed at months 0, 2, 6, 9, and 18 and cTnI and CRP measured every 2 weeks during chemotherapy then at months 6, 9, and 18. These biomarkers were correlated with changes in LVEF. Results: Ninety-five patients enrolled. Overall, 3 (3%) patients withdrew during AC and 41 (43%) withdrew during PTL→TL, mostly due to diarrhea. Median LVEF was 68% (baseline), 69% (month 2), 65% (month 6), 65% (month 9), and 65% (month 18). The majority (67%) had a detectable cTnI during the study. The proportion of detectable cTnIs increased over time; 4% at baseline, 11% at month 2, and 50% at month 3. The timing of these detectable cTnIs preceded maximum-recorded decline in LVEF. However, overall, maximum cTnI levels did not correlate with LVEF declines. A detectable CRP was seen in 74/95 (78%) but did not correlate with LVEF declines. Conclusion: In patients receiving ddAC→PTL, cTnIs are commonly detected. These elevations may precede changes in LVEF but, as assessed in this trial, do not predict CHF. Clin Cancer Res; 17(10); 3490–9. ©2011 AACR.Keywords
This publication has 35 references indexed in Scilit:
- Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I EvaluationJournal of Clinical Oncology, 2010
- Dose-Dense Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/neu–Overexpressed/Amplified Breast Cancer Is Not Feasible Because of Excessive DiarrheaJournal of Clinical Oncology, 2010
- Dose-Dense Adjuvant Doxorubicin and Cyclophosphamide Is Not Associated With Frequent Short-Term Changes in Left Ventricular Ejection FractionJournal of Clinical Oncology, 2009
- Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial InfarctionThe New England Journal of Medicine, 2009
- Neuregulin-1β Is Associated With Disease Severity and Adverse Outcomes in Chronic Heart FailureCirculation, 2009
- American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late EffectsJournal of Clinical Oncology, 2007
- Prevention of High-Dose Chemotherapy–Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme InhibitionCirculation, 2006
- Prognostic Value of Troponin I in Cardiac Risk Stratification of Cancer Patients Undergoing High-Dose ChemotherapyCirculation, 2004
- Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741Journal of Clinical Oncology, 2003
- Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapyJournal of the American College of Cardiology, 2000