Cardiac toxicity of trastuzumab in elderly patients with breast cancer

Breast cancer (BC) is diagnosed in 65 year old or older women in about half of cases. The current view is that systemic therapy should be offered to these patients, if it can be reasonably anticipated based on their overall conditions and life expectancy that the benefits of treatment will outweigh risks. For elderly like young subjects with BC overexpressing human epidermal growth factor receptor-2 (HER-2), the monoclonal antibody against HER-2, trastuzumab, represents a valid therapeutic option. Unfortunately, administration of this drug is associated with occurrence of left ventricular dysfunction and chronic heart failure (CHF), possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective studies have reported an incidence of CHF of around 25% in old trastuzumab recipients compared with 10-15% in women of comparable age, but not receiving any therapy for BC, and the risk of CHF in trastuzumab users vs. non-users has been estimated to be two-fold higher. Extremely advanced age and preexisting cardiac disease has been shown to predispose to trastuzumab cardiotoxicity. Clearly, it is mandatory that only patients with proved HER-2 positive BC are prescribed trastuzumab, in order not to expose to unjustified risk of cardiac side effects. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. With this respect, the role of selected biomarkers or new imaging techniques (3D, tissue velocity, and strain echocardiography, magnetic resonance imaging) is promising, but must be further investigated in general and specifically in the elderly. At the preclinical level, a better understanding of the mechanisms by which trastuzumab affects the old heart are warranted.