P315Early Trastuzumab-induced cardiotoxicity in breast cancer patients.

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Background: Trastuzumab (TZB) is a recombinant humanized monoclonal antibody used for the treatment of HER2-positive breast cancer. In spite of its recognized cardiotoxicity, pathophysiological mechanisms explaining side effects remain poorly understood and the methods for its early sub-clinical detection are not well defined.Aim: To evaluate TZB-induced cardiotoxicity in patients (pts) with breast cancer followed for a 3-month period of treatment.Methods: Prospective study (evaluation of cardiotoxicity induced by chemotherapy - ACT-QT study) of consecutively pts, enrolled between May and September 2010, treated with TZB for advanced HER2-positive breast cancer. A comparison of clinical, laboratorial and echocardiographic data, prior and at the 3rd month after starting TZB was performed. Left ventricular systolic function deterioration (LVSF), defined according to the criteria established by the CREC - Cardiac Review and Evaluation Committee, and diastolic function, under the classification proposed by ASE – American Society of Echocardiography, were studied. Hospitalization and mortality were also analyzed.Results: Data were available for 51 women, mean age=55.4±14.0y. At 3 months, no pts had symptomatic heart failure. LVSF by Simpson biplane formula calculation did not differ at 3-months (69.3±7.4 vs 67.1±6.5 %, p>0.05), decreasing in 57.9% pts (only one to left ventricular ejection fraction <55%); 19.4% pts developed impaired ventricular relaxation, with a significant increase in E/e' ratio (3.9±0.8 vs 8.0±1.9, p<0,001). Pericardial effusion was present in five pts at the 3rd month (>1mm). Both left atrial and left ventricle volumes remained unchanged after TZB treatment. N-terminal pro-B type natriuretic peptide values did not increase. During the follow up two pts died and two were admitted to the hospital, both for non-cardiovascular causes.Conclusion: During the first 3 months of TZB treatment none of the pts presented overt heart failure or significant LVSF deterioration although almost one-fifth of them developed impaired ventricular relaxation, eventually as an early sign of TZB-induced cardiotoxicity.

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