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 ≥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.