Abstract:

Human epidermal growth factor receptor -2 (HER-2) is a member of EGFR (epidermal growth factor receptor) family, plays a very significant role in cell growth and proliferation [1] HER – 2 protein is over expressed in 20% of breast cancer and is associated within aggressive course , poor prognosis and response to treatment [2-3]. The introduction of transtuzumab, a monoclonal antibody directed against, the extra cellular domain of HER -2 receptor, has revolutionized the treatment of HER – 2 positive early breast cancer and has led to significant improvement in disease free survival and overall survival over chemotherapy alone. 

In randomized multicenter trials with HER – 2 over expressing metastatic breast cancer patients, addition of transtuzumab to first line chemotherapy has improved objective response rate, the time to disease progression and overall survival over chemotherapy alone [4,5]. Hence transtummab is now considered as the standard of care for all patients who over amplify HER – 2 neu receptors.

These benefits have come with the cost of increased risk of cardiotoxicity. Transtuzumab related cardiotoxicity is mediated by interruption of normal HER – 2 signaling pathway in the heart, which is responsible for maintenance of normal growth, repair and survival of cardiomyocytes. Cardiotoxicity related to transtuzumab is different from that of anthracyclins as it is not dose related and appears to be largely reversible on discontinuation of therapy. There is no alteration is ultra structural abnormalities where as that due to anthracyclins are caused by free radical induced oxidative stress to cardiac muscles cells [12]. 

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