New prognostic factor for predicting trastuzumab-induced cardiotoxicity

2 Sep 2010

By Dr Sharan Sharma

The introduction of trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) has radicalised the treatment of HER2 over expressing breast cancer which has generally poor prognosis. At present, trastuzumab is considered part of the standard therapy for both advanced and early breast cancer. Its use, however, has resulted in an unexpectedly high incidence of cardiotoxicity, usually occurring as asymptomatic left ventricular ejection fraction (LVEF) reduction or overt heart failure (HF). The incidence of trastuzumab-induced cardiotoxicity (TIC) has been reported to be as high as 34%.In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. A new paper from researchers of European institute of Oncology published in the current issue of Journal of Clinical Oncology tries to answer this crucial question. They investigated the role of Troponin I (TNI) to stratify patients at risk for TIC.

The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Researchers enrolled a total of 251 women. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated.

The result showed that TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC and of lack of LVEF recovery. About the implication of this study the authors note "The study provided us with a marker assessment of which during trastuzumab therapy allows for identification of patients at risk of cardiotoxicity as well as of those who, despite HF therapy, will not recover from cardiac dysfunction."