Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer.

Trastuzumab (Herceptin) is a humanised monoclonal antibody that specifically targets HER2-positive breast cancer cells. Safety data collected from pivotal trials with trastuzumab indicate that this therapy is generally well tolerated. However trials of the combination of trastuzumab plus chemotherapy, and in particular chemotherapy with anthracyclines, have revealed an elevated incidence of cardiotoxicity in some patients, which was not apparent in preclinical or early clinical studies. Analyses of the available data suggest that in most cases the cardiotoxicity observed may reflect an exacerbation of anthracycline-induced cardiotoxicity. The biological mechanism of the cardiotoxicity has been investigated in several studies, and current data indicate that the heregulin/HER2-signalling pathway may have an important role. It is of note that the cardiotoxicity is generally reversible and can usually be managed with standard medical treatment. Improvement in cardiac function is seen both in patients who continue trastuzumab and in those in whom further therapy is withdrawn, indicating that with careful management anticancer therapy can be continued.