Trastuzumab and cardiotoxicity

Trastuzumab and cardiotoxicity

Trastuzumab and cardiotoxicity: Trastuzumab is useful for the chemotherapy of breast cancers which are HER2 (human epidermal growth factor receptor-2) positive, which constitute about one fifth of cases of breast cancer. Untreated, HER2 positive cases have a poorer prognosis than negative cases [Moja L et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012 Apr 18; 4:CD006243]. Adding trastuzumab as an adjuvant chemotherapeutic agent for one year has a significant impact on improving survival in HER2 positive breast cancer [Smith I et al (HERA Study team). 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6; 369(9555):29-36].

There is a medium risk for development of cardiotoxicity with this monoclonal antibody. Most often it takes the form of asymptomatic left ventricular dysfunction documented on echocardiography while rarely clinical heart failure may also follow therapy with Trastuzumab. Severe heart failure / death is reported only in 0.6 to 4% in different studies. Risk is likely to be higher in those who have received doxorubicin therapy earlier. Trastuzumab causes type II cardiotoxicity which may not be dose dependent, but reversible. HER2 receptors present on the myocytes may have role in cardiotoxicity.

Type I cardiotoxicity is irreversible and caused by death of cardiomyocytes, through necrosis or apoptosis. Type II cardiotoxicity may be reversible as it is caused by cardiomyocyte dysfunction and not cell death. Long term cardiotoxicity of anthracyclines is of type I with cell death mediated by free radical formation and hence likely to be irreversible [Maria Volkova et al. Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment. Curr Cardiol Rev. Nov 2011; 7(4): 214–220].