Adjuvant trastuzumab induces ventricular remodeling despite aerobic exercise training.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Haykowsky
Mark J
MJ
Faculty of Rehabilitation Medicine and Department of Biomedical Engineering, University of Alberta, Edmonton, AlbertaT6G 2G4, Canada. mark.haykowsky@ualberta.ca
Mackey
John R
JR
Thompson
Richard B
RB
Jones
Lee W
LW
Paterson
D Ian
DI
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000517:prevention & control; D020257:Ventricular Remodeling / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human