Risk factors for the occurrence and irreversibility of cardiotoxicity caused by trastuzumab therapy

Cardiotoxicity is the most important side effect of trastuzumab, humanized monoclonal antibody to the HER2 protein, in use for immunotherapy of breast cancer. It is mainly manifested as a reduction in left ventricular contractility without myocardial necrosis and the process is therefore mostly reversible. However, sometimes the disease can progress to irreversible dilated cardiomyopathy. So far, many risk factors explaining cardiotoxicity have been identified, but it is still unclear how to assess individual risk. Also, there are no defined factors that can predict irreversibility of the disease. Pts with D/D ACE genotype, tumor of the left breast and positive family history of cardiovascular disease have a higher risk of developing cardiotoxicity with trastuzumab therapy and should be treated as high risk pts. Trastuzumab induced cardiotoxicity ismore likely to be irreversible in pts with a more extensive decrease of the LVEF and a higher serum NT-proBNP level. The time between prior chemotherapy and administration of trastuzumab shorter than 30 days ismore often associated with irreversible cardiac impairment.