Is cardiotoxicity being adequately assessed in current trials of cytotoxic and targeted agents in breast cancer?

The cardiotoxicity of anthracyclines, trastuzumab and other agents is of special importance to adjuvant breast cancer patients whose life expectancy is restored to normal but who may be left with cardiac abnormalities that can present years later. We systematically reviewed the design of current trials (including adjuvant studies) on the clinicaltrials.gov Web site. Surprisingly few specify primary or secondary cardiac end points. Although cardiac ultrasound (echocardiography) and multiple uptake gated acquisition scintigraphy remain the most frequent techniques for estimating left ventricular ejection fraction, there is no consistency in the degree of reduction from baseline or absolute value taken as indicating cardiotoxicity. The details given do not suggest that diastolic function (which may give earlier warning of problems) is a focus of interest. There is growing interest in troponin as a marker of myocyte death and brain natriuretic peptide as a marker of myocardial stress and possible heart failure (though their clinical usefulness has still to be adequately defined). The duration of follow-up in many adjuvant studies may not be sufficient to determine the risk of late cardiac events. The findings indicate a need to study and standardize cardiac toxicity assessments in oncology trials.