Trastuzumab is a monoclonal antibody that targets the human epidermal growth 
factor receptor tyrosine kinase HER2/ErbB2. This agent has shown a highly 
significant antitumour effect for patients with HER2-positive breast cancer, and 
is now considered part of the standard regimens for the treatment of this 
disease in both the metastatic and adjuvant setting. Cardiotoxicity has been 
associated with trastuzumab, and this issue has now been studied and documented 
in a number of adjuvant trials for which data have now been released. 
Cardiotoxicity has been shown to be potentiated when the agent is used 
concurrently or sequentially with an anthracycline, and this has limited the use 
of trastuzumab in some patients. Determining the overall impact of trastuzumab 
is further complicated by the administration of other cardiotoxic agents such as 
the taxanes and cyclophosphamide as well as by pre-existing cardiac disease. The 
incidence of severe congestive heart failure (New York Heart Association class 
III or IV) was 0-3.9% in the trastuzumab arms versus 0-1.3% in the control arms 
in the five major randomized adjuvant trials. Only one cardiac death was related 
to trastuzumab whereas two cardiac deaths occurred in the control arms. Ejection 
fraction decline of >or=10% or 15% was reported in 3-34% of trastuzumab 
recipients in these trials. Patients affected by trastuzumab-related 
cardiotoxicity do not exhibit the cellular death and distinctive ultrastructural 
myocardial changes seen on electron microscopy with anthracycline-induced 
cardiotoxicity. The cardiotoxicity of trastuzumab also differs from traditional 
chemotherapy-induced cardiotoxicity in that it appears to be at least partially 
reversible, not related to the cumulative dose, and re-challenge is generally 
tolerated. There remain a number of uncertainties regarding the diagnosis and 
management of trastuzumab-related cardiotoxicity. While no formal guidelines or 
consensus statements exist at present regarding cardiac monitoring during use of 
trastuzumab, proposed recommendations include a careful assessment of ejection 
fraction prior to initiating trastuzumab, avoidance of concurrent administration 
of trastuzumab with anthracyclines, and regular monitoring of symptoms and 
cardiac function during and for several years after therapy. Increased vigilance 
is appropriate for higher risk patients.