Exercise has numerous benefits for patients with cancer, but implementation is challenging because of practical and logistical hurdles. This study examined whether neuromuscular electrical stimulation (NMES) can serve as a surrogate for classical exercise by eliciting an exercise training response in skeletal muscle of women diagnosed with breast cancer undergoing chemotherapy. Patients (n = 22) with histologically-confirmed, stage I, II or III breast cancer scheduled to receive neoadjuvant or adjuvant chemotherapy were randomized to 8 weeks of bilateral neuromuscular electrical stimulation (NMES; 5 days/week) to their quadriceps muscles or control. Biopsy of the vastus lateralis was performed at baseline and after 8 weeks of intervention to assess muscle fiber size, contractility and mitochondrial content. Seventeen patients (8 control/9 NMES) completed the trial and were included in analyses. NMES promoted muscle fiber hypertrophy (p < 0.001), particularly in fast-twitch, myosin heavy chain (MHC) IIA fibers (p < 0.05), and tended to induce fiber type shifts in MHC II fibers. The effects of NMES on single muscle fiber contractility were modest and it was unable to prevent declines in function in MHC IIA fibers. NMES did not alter intermyofibrillar mitochondrial content/structure, but was associated with reductions in subsarcolemmal mitochondria. Our results demonstrate that NMES induces muscle fiber hypertrophy and fiber type shifts in MHC II fibers, but had minimal effects on fiber contractility and promoted reductions in subsarcolemmal mitochondria. Further studies are warranted to evaluate the utility of NMES as an exercise surrogate in cancer patients and other conditions.

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