Evaluation of QTc Interval Prolongation in Breast Cancer Patients after Treatment with Epirubicin, Cyclophosphamide, and Docetaxel and the Influence of Interobserver Variation

Abstract

Background: Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation. Patients and Methods: In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel. To evaluate the influence of interobserver variation, the QTc interval was analyzed by a cardiologist, a gynecologist, and with automated ECG interpretation software. Results: There was a significant QTc prolongation after EC treatment independent of the investigator. In addition, a significant increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels was noted after EC treatment. QTc prolongation and NT-proBNP levels normalized after docetaxel treatment. Other biochemical markers were within normal ranges. No clinically relevant effect on left ventricular ejection fraction was observed. Conclusion: This prospective study demonstrated that EC treatment increases the QTc interval and NT-proBNP levels in women with early breast cancer. This effect was reversible and independent of docetaxel administration. Moreover, the treating physician can safely perform QTc interval evaluation as part of clinical routine independent of his/her specialty. Due to the small number of patients, further conclusions are limited at this point.