Muscle oxygen uptake and recovery kinetics during plantar flexion exercise in long-term breast cancer survivors previously treated with cardiotoxic therapy

Abstract Background Reduced aerobic endurance in older breast cancer survivors (BCS) has been primarily attributed to cardiac factors; however, the role of skeletal muscle impairments has been less studied. Purpose To compare muscle oxygen uptake (mVO2) and post exercise recovery kinetics, using magnetic resonance imaging (MRI), during and after maximal plantar flexion exercise in long-term BCS compared with healthy age-matched non-cancer controls (CON). Methods Older (≥60 years) female BCS who were at least one-year post-completion of cardiotoxic treatment (anthracycline chemotherapy and/or trastuzumab) were recruited (n = 31), along with age-matched female CON (n = 10). BCS had a lower resting left ventricular ejection fraction (LVEF, 59.9 ± 6.1 vs. 68.3 ± 10.7%, P=0.003). All participants completed an incremental to maximal plantar flexion exercise test with functional magnetic imaging assessment (phase contrast, susceptometry-based oximetry in the popliteal vein) of peak exercise calf muscle blood flow, arterial venous oxygen difference (a-vO2 Diff) and mVO2, while recovery kinetics for mVO2, blood flow and a-vO2 were determined as half-time recovery values - defined as the time taken to reach the mid point amplitude between peak values and recovery (OriginLab software). All outcomes for BCS and CON were compared using two-tailed independent t-tests, and the association between peak mVO2 and recovery kinetics were assessed using Pearson correlations. P<0.05 was considered statistically significant. Results BCS were studied, on average, 14.3 ± 5.3 years post-cardiotoxic treatment and were well matched with CON for age (69.6 ± 5.1 vs. 68.8 ± 5.2 years, respectively; P = 0.67) and body mass index (27.2 ± 5.7 vs. 26.1 ± 5.5 kg/m², P = 0.53). No significant differences were found between groups for peak calf muscle blood flow (BCS: 503 ± 148 vs CON: 470 ± 180 mL/min, P=0.56; Fig 1A), a-vO2 difference (BCS: 6.1 ± 1.1 vs CON: 6.2 ± 0.9 mL/dL, P=0.86; Fig 1B), or mVO2 (BCS: 30.9 ± 10.9 vs CON: 29.5 ± 13.7 mL/min, P=0.73; Fig 1C). Following exercise termination, mVO2 recovery kinetics were also not different between groups (BCS: 34.1 ± 8.5 vs CON: 31.8 ± 11.1 sec, P=0.51; Fig 1D). There were no significant associations between peak calf mVO2 and the recovery halftime kinetics (mVO2, muscle blood flow, and a-vO2 Diff – Fig 2) within the BCS or CON groups. Conclusions Long-term BCS survivors previously treated with cardiotoxic therapy have preserved peak muscle blood flow, oxygen extraction, mVO2, and mVO2 recovery kinetics during small muscle mass exercise. These findings suggest that reduced aerobic endurance in long term BCS is not due to impairments in small muscle function, but may be due to other factors such as deficits in cardiac and/or large muscle structure or function,Figure 1.  Figure 2