Chemotherapy Plays a Role in Skeletal Muscle Atrophy in Patients With Breast Cancer

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Treatment with chemotherapeutics promoted atrophy and mitochondrial damage in breast muscle cells.
Treatment with chemotherapeutics promoted atrophy and mitochondrial damage in breast muscle cells.

Chemotherapies commonly used in the treatment of breast cancer may adversely affect the skeletal muscle of women receiving these therapies, according to a small study.1

The study assessed the skeletal muscle structure and protein expression of 13 women with breast cancer who had undergone adjuvant chemotherapy after tumor resection. Muscle structure was compared with 12 women without breast cancer.

The researchers hypothesized that cancer treatments might promote skeletal muscle adaptions, and might have myotoxic effects as a result of mitochondrial dysfunction and oxidative stress.

Women with breast cancer were found to have a reduced single muscle fiber cross-sectional area compared with controls (P < .05). In addition, women with breast cancer had reduced fractional content of both subsarcolemmal (P < .05) and intermyofibrillar mitochondria (P < .03).

“Interestingly, different structural characteristics accounted for reduced mitochondrial content in subsarcolemmal and intermyofibrillar compartments in breast cancer patients, suggesting different mechanisms for mitochondrial remodeling in the 2 compartments,” the researchers wrote.1

To address whether chemotherapeutics promoted mitochondrial loss through the ability to provoke mitochondrial dysfunction and oxidant production, the researchers used C2C12 myotubes. They found that 2 commonly used breast cancer treatment drugs — doxorubicin and paclitaxel — caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species production in C2C12 murine myotube cell cultures (P < .05).

The researchers also found that treatment of the myotubes with mitochondrial-targeted antioxidant prevent this chemotherapy-induced myosin depletion, mitochondrial loss, and reactive oxygen species (ROS) production.

“Our results provide evidence for skeletal muscle atrophy and mitochondrial rarefaction in breast cancer patients that may be linked to the mitotoxic effects of chemotherapeutics,” the researchers concluded. “From a clinical standpoint, these adaptations may contribute to muscle weakness (atrophy) and fatigue (mitochondrial).”

Interventions to counter these effects should be developed to alleviate burden of disease, the authors added.

Reference

  1. Guigni BA, Callahan DM, Tourville TW, et al. Skeletal muscle atrophy and dysfunction in breast cancer patients: Role for chemotherapy-derived oxidant stress [published online September 12, 2018]. Am J Physiol Cell Physiol. doi:10.1152/ajpcell.00002.2018

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