Echocardiography signs of early cardiac impairment in patients with breast cancer and trastuzumab therapy

Objective Recent studies in breast cancer patients and Trastuzumab therapy (Herceptin) showed a development of a toxic cardiomyopathy as a severe complication. The aim of this study was to discover early changes in cardiac function and morphology. Methods We studied 42 female patients with Her-2/-neu over-expression in breast cancer by echocardiography before, 3, and 6 months after start of the adjuvant Herceptin therapy. All values were mean value +/- A standard deviation. Results After 3 or 6 months of a trastuzumab therapy we discovered significant increases in the diastolic and systolic left ventricle volume indices (LV-DVI 32.4 +/- 8.5 vs. 38.5 +/- 8.7 vs. 40.3 +/- 10.3 ml/m(2), p < 0.001 and LV-SVI 12.6 +/- 4.0 vs. 15.7 +/- 4.7 vs. 17.2 +/- 6.8 ml/m(2), p < 0.001), an increase of the end-diastolic and end-systolic LV diameter (LVEDD 46.8 +/- 4.2 vs. 48.0 +/- 4.7 vs. 49.7 +/- 4.5 ml/m(2), p < 0.01; LVESD 28.3 +/- 4.2 vs. 31.0 +/- 4.7 vs. 32.3 +/- 4.9 mm, p < 0.001), a reduced systolic ventricle function determined by the tissue Doppler imaging (TDI) velocity (9.2 +/- 2.5 vs. 8.0 +/- 1,7 vs. 7.7 +/- 1.5 cm/s, p < 0.001), fractional shortening (39,6 +/- 7.5 vs. 35.4 +/- 7.4 vs. 35.2 +/- 7.0%, p < 0.01), and the LV-EF Simpson biplane [62.0 +/- 5.1 vs. 60.1 +/- 6.3 ( p = ns) vs. 58.4 +/- 7.9%, p < 0.01] compared to pretreatment values. There was also an increase of the left atrial volume index (21.4 +/- 6.2 vs. 26.2 +/- 7.9 vs. 29.7 +/- 8.8 ml/m(2), p < 0.001), a decrease of the median TDI atrial velocities (11.9 +/- 2.4 vs. 10.5 +/- 2.8 vs. 10.1 +/- 2.1 cm/s, p < 0.01), an increase of the peak early diastolic filling velocities (73.1 A 15.4 vs. 83.1 +/- 16.4 vs. 82.2 +/- 19.4 cm/s, p < 0.05), and an increase of the median mitral valve insufficiency degree (0.64 +/- 0.65 vs. 1.03 +/- 0.76 vs. 1.11 +/- 0.73 degrees, < 0.001). We could not detect a significant increase in diastolic dysfunction. Also right heart diameters and function did not change significantly. Most patients stayed in an asymptomatic stage of cardiac disease. Conclusion The blockade of Her2/-neu receptors with trastuzumab in patients with breast cancer led to measurable alterations of left ventricular volume, left atrial volume, and systolic function as early as 3 months after start of treatment.