Dual anti- HER2 therapy with trastuzumab and pertuzumab in combination with taxane-based chemotherapy improves overall survival in patients with metastatic HER2-positive breast cancer. There is a critical need to investigate the potential cardiotoxicity of dual anti-HER2 blockade, given the importance of HER2 signaling in cardiac homeostasis and stress response. Sequential left ventricular (LV) ejection fraction (EF) assessment has been mandated to detect myocardial dysfunction. Changes in cardiac function induced by this therapy, however, are subtle and difficult to quantitate by conventional imaging methods. Doppler myocardial imaging-based velocity, strain, and strain rate measurements have been shown to sensitively quantify abnormalities in cardiac function in other settings. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically strain rate imaging, would be useful for addressing the early detection of dual anti-HER2 mediated cardiotoxicity.
Patients with 0-1 lines of prior therapy were treated with 8 cycles of docetaxel (75mg/m(2) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks. Conventional and Doppler myocardial imaging echocardiography were obtained at baseline and every 2 cycles of treatment. Segmental peak systolic longitudinal and radial velocity, strain, and strain rate (SR) were measured.
Twenty-seven women (median age 52.2 years) were enrolled in the study. There was no overall change in Left ventricular dimensions, ejection fraction, and systolic myocardial velocity. In contrast, a significant reduction in longitudinal and radial strain and strain rate was found after 8 cycles (longitudinal strain -12.8% +/- 2.2% vs baseline (P = .001); radial strain 29.3% +/- 7.1% vs 50.3% +/- 10.6%, P < .001 vs baseline). Changes in radial function appeared earlier and were more pronounced than in longitudinal direction.
In contrast with conventional echocardiography myocardial velocity measurements allowed detecting subtle changes in longitudinal and radial left ventricular function after 8 cycles of therapy. We suggest that strain rate imaging identifies preclinical myocardial dysfunction earlier than conventional measures in women undergoing treatment with dual anti-HER2 therapy for metastatic breast cancer and could be used for cardiac function monitoring.
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All authors have declared no conflicts of interest.