Detection of Early Sub-Clinical Trastuzumab-Induced Cardiotoxicity in Breast Cancer Patients

Background: Trastuzumab (TZB) is a recombinant humanized monoclonal antibody, used for the treatment of HER2-positive breast cancer, with recognized associated-cardiotoxicity. The methods for its early sub-clinical detection are not well defined. Objective: To evaluate TZB-induced cardiotoxicity in patients (pts) with breast cancer followed for a 3-month period of treatment. Methods: Prospective study of consecutive pts treated with TZB for advanced HER2-positive breast cancer enrolled between May-September/2010. A comparison of clinical, laboratory and echocardiographic data, prior to and at the 3rd month after starting TZB was performed. Left ventricular systolic function deterioration (Cardiac Review and Evaluation Committee criteria) and diastolic function (American Society of Echocardiography classification) were studied. Results: Data were available for 51 women, mean age = 55.4 +/- 14.0y. At the 3rd month, no patient had symptomatic heart failure. Left ventricular ejection fraction (LVEF) 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 LVEF < 55%). There was a significant increase in the E/e' ratio (3.9 +/- 0.8 vs. 8.0 +/- 1.9, p < 0,001) due to an e'velocity reduction (0.19 +/- 0.02 vs. 0.10 +/- 0.03, p < 0.001). Other diastolic parameters remained unchanged. Both the left atrial and the left ventricular volumes remained unchanged. N-terminal pro-B type natriuretic peptide levels did not increase. During the follow up period two pts died and two were admitted to the hospital, all for non-cardiovascular causes. Conclusion: During the first 3 months of TZB treatment none of the pts presented overt heart failure or significant LVEF deterioration. A significant reduction in the E/e' ratio was detected, but neither the loading parameters nor LVEF changed significantly.