Trastuzumab versus lapatinib: The cardiac side of the story

HER2 gene plays a pivotal role in the pathogenesis of 20% of breast cancer patients. At the same time, it is one of the main cardiac survival pathways when subjected to bio-mechanical stress including exposure to anthracyclines. With the emergence of the anti-HER2 targeting agents, concerns raised regarding the potential cardiac toxicities of these drugs. In the early clinical trials with trastuzumab, it was evident that it has a significant cardiac toxicity. The incidence of symptomatic heart failure ranged from 4% to 7% with trastuzumab alone, and 27% when administered concurrently with doxorubicin. On the other hand, available data suggest that lapatinib is much less cardiotoxic. The incidence of symptomatic heart failure has been constantly reported to be less than 0.5%. In this review, we discuss the possible theories behind the differences in the cardiac profile of both agents. We emphasize on the role of cardiac bioenergetics and the effects of trastuzumab and lapatinib on ATP production through the different effects they exert on the cardiac mitochondria. (C) 2009 Elsevier Ltd. All rights reserved.