Adjuvant Trastuzumab Induces Ventricular Remodeling Despite Aerobic Exercise Training

Purpose: To examine the effect of aerobic training in mitigating trastuzumab-mediated left ventricular (LV) remodeling in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Experimental Design: Seventeen women (53 +/- 7 years) with HER2-positive breast cancer did aerobic training during the first 4 months of adjuvant trastuzumab. Peak oxygen consumption and magnetic resonance imaging assessment of LV volumes, mass, and rest and peak (dobutamine stress) ejection fraction were assessed before and after 4 months of trastuzumab. Results: Participants attended 59% +/- 32% of prescribed exercise sessions at 78% +/- 6% of peak heart rate. Peak exercise heart rate, systolic and diastolic blood pressure, power output, and oxygen consumption were not different after training (all P-values> 0.05). Exercise adherence predicted change in peak oxygen consumption (r = 0.77; P= 0.000). Resting end-diastolic (pre: 120 +/- 23 mL versus post: 133 +/- 16 mL) and end-systolic volumes (pre: 44 +/- 12 mL versus post: 55 +/- 11 mL) and mass (pre: 108 +/- 21 g versus post: 114 +/- 18 g) increased, whereas ejection fraction (pre: 64% +/- 4% versus post: 59% +/- 4%) decreased from baseline to post-intervention (all P-values < 0.05). Peak ejection fraction was lower after 4 months (pre: 79 +/- 4 versus post: 76 +/- 6%; P= 0.087). Conclusion: Initiation of adjuvant trastuzumab therapy is associated with LV cavity dilation and reduced ejection fraction despite aerobic exercise training. The long-term consequences of trastuzumab-induced LV remodeling and the means to prevent LV dysfunction require further study.