Cancer therapy cardiotoxicity detection: understanding the limitations of cardiac imaging

Patients with breast cancer who overexpress human epidermal growth factor receptor 2 (HER2) are often treated with sequential anthracyclines followed by trastuzumab. This has led to significant improvements in mortality with an increasing number of breast cancer survivors. One of the major toxicity concerns with the use of both anthracyclines and trastuzumab is a decline in left ventricular ejection fraction (LVEF), commonly referred to as cancer-therapeutic-related cardiac dysfunction (CTRCD). Initial concerns from clinical trial results in patients with metastatic breast cancer treated with concurrent anthracycline and trastuzumab reported cardiotoxicity levels up to 27%.1 This led to stricter inclusion and exclusion criteria, with rather arbitrary LVEF cut-offs for the use of trastuzumab as adjuvant therapy. However, in later clinical trials, anthracycline and HER2 inhibitor treatment were separated into sequential therapy cycles rather than concomitant use. This strategy along with reduction in the cumulative dose of anthracyclines has been associated with a significant decrease in the incidence of cardiotoxicity. Based on the cardiac monitoring performed during the adjuvant therapy trials, it is now recommended that patients have serial LVEF assessment every 3 months while on trastuzumab. This leads to at least four echocardiograms for patients receiving adjuvant trastuzumab for 1 year and may be many more for patients with metastatic breast cancer receiving trastuzumab for years. The clinical trials used either nuclear multi-gated acquisition or echocardiograms for LVEF measurements; however, at present the general standard is to preferentially use echocardiography given its lack of radiation, portability, low cost and widespread availability. Although cardiac magnetic resonance (CMR) imaging has been considered the gold standard for LVEF assessment, and is often used as the standard in research studies evaluating the accuracy of echocardiographic derived LVEF, its lack of availability and relative higher cost limit its routine clinical use for cardiac monitoring. Several definitions of …