Blood flow and oxygen (O2) extraction in the lower leg skeletal muscles of patients with breast cancer adapt to chemotherapy-related hemoglobin reduction for small muscle mass exercise; however, these changes are not sufficient to support large muscle mass exercise, which can lead to exercise intolerance and potentially long-term metabolic impairment (suppressed fat oxidation leading to insulin resistance). These findings were published in The Oncologist.

A team of researchers investigated the effects of cardiotoxic chemotherapy on the musculoskeletal system of patients with breast cancer. Their study was designed to assess the longitudinal skeletal muscle changes in early-stage breast cancer patients across chemotherapy treatment.

For this study, 34 female patients with stage I-III breast cancer who were receiving chemotherapy were enrolled and assigned to a multidisciplinary care intervention group (14 patients) and a usual care group (20 patients). These patients were part of a larger parent study. The researchers also evaluated 16 patients as a control group.

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Magnetic resonance imaging was used to noninvasively measure thigh myosteatosis (fat-water imaging), and lower leg metabolism (31P spectroscopy), O2 consumption (custom techniques), and peak power output during single-leg plantarflexion exercise. Peak exercise pulmonary oxygen uptake (VO2peak) and maximal leg press strength were also assessed.

Assessments were obtained prior to trastuzumab-containing and/or anthracycline-containing chemotherapy (baseline), at the midpoint of treatment (approximately 2 to 3 weeks after cycle 3 or approximately 9 to 10 weeks after baseline), and after chemotherapy (approximately 24 weeks after baseline), as well as at 1 year postbaseline. A single scan using identical protocols was performed in patients in the control group.

Results showed hemoglobin reduction was substantial at midtreatment and remained lower than baseline through 1 year postbaseline. Significant decreases in VO2peak and leg press strength after chemotherapy also were noted. Lower leg skeletal muscle blood flow and O2 extraction adapted to compensate for the hemoglobin reduction when it came to small muscle mass exercise. But the association between exercise cardiac output and cardiotoxic chemotherapy limit the blood flow needed for large muscle mass exercises such as leg press and cycling.

“This study demonstrated that anthracycline or trastuzumab-containing chemotherapy results in skeletal muscle energy metabolism and O2 extraction/utilization perturbations in response to chemotherapy-related reduced hemoglobin,” explained the researchers. “Blood flow and O2 extraction increase to maintain O2 delivery and consumption and power output during small muscle mass exercise but cannot fully compensate for exercise utilizing large muscle mass, as evidenced by reductions in pulmonary VO2peak and leg press 1-RM with chemotherapy.”

Further research could delve into the “potential defects in the fat oxidation pathway and to test nutritional and exercise strategies to upregulate fat oxidation during chemotherapy for breast cancer.”

This study was limited by its small sample size. But the results suggest that physical activity that does not involve large muscle mass could be helpful for patients while hemoglobin levels are suppressed by chemotherapy.


Kirkham AA, Pituskin E, Mackey JR, et al. Longitudinal changes in skeletal muscle metabolism, oxygen uptake, and myosteatosis during cardiotoxic treatment for early-stage breast cancer. Oncologist. Published online May 17, 2022. doi:10.1093/oncolo/oyac092