Effects Of 12-months Of Exercise Training On Determinants Of Vo2Peak In Anthracycline-treated Breast Cancer Survivors

PURPOSE: Reduced peak oxygen uptake (V̇O2peak) is common in breast cancer (BC) survivors treated with anthracycline chemotherapy (AC). Exercise training (ExT) may be a useful therapy for addressing reduced V̇O2peak, however the mechanisms underlying changes in V̇O2peak with exercise training (ExT) during AC are unclear. We sought to evaluate the effect of ExT on the central (convective O2 delivery [QO2]) and peripheral (arterio-venous O2 difference [a-vO2diff] and skeletal muscle diffusive conductance [DmO2]) determinants of V̇O2peak in female BC survivors. METHODS: This was a secondary analysis of the BREXIT study using baseline (pre-AC) and 12-month assessments from a 12-month randomized trial comparing 3-4 sessions/wk of aerobic and resistance ExT to usual care (UC) in 104 women aged 40-75 years with stage I-III BC scheduled for AC. V̇O2peak, peak heart rate (HRpeak) and arterial O2 saturation were assessed from an upright cardiopulmonary exercise test. Peak cardiac output (Qpeak) was calculated from upright HRpeak and supine peak stroke volume (SVpeak) during exercise cardiac magnetic resonance. Hemoglobin (Hb) was measured from a venous blood sample. These measures were then used to calculate a-vO2diff, QO2 and DmO2 from previously published equations. RESULTS: Sixty-four participants completed the study with available data to calculate V̇O2peak determinants (ExT: n = 38, UC: n = 26). At 12-months, ExT had a significant effect on V̇O2peak (+0.17 L/min) due to a 0.08 L/min increase with ExT (P = 0.03) and a 0.08 L/min reduction with UC (P = 0.03). Changes in V̇O2peak were largely driven by QO2, and specifically Qpeak, that increased with ExT (+1.3 L/min, P < 0.001) and decreased with UC (-1.6 L/min, P < 0.001), resulting in a 3.0 L/min (P < 0.001) and 0.33 L/min (P < 0.001) net benefit of ExT on Qpeak and QO2, respectively. In contrast, there was a small reduction in a-vO2diff with ExT (-0.5 mL/dL, P = 0.038) and an increase with UC (+0.6 mL/dL, P = 0.042), resulting in a net decline with ExT (-1.1 mL/dL, P < 0.001). These effects were largely driven by Qpeak, as DmO2 did not change during the study. CONCLUSIONS: In early-stage BC survivors undergoing AC, treatment-induced reductions in V̇O2peak are largely driven by a decline in QO2 secondary to reduced Qpeak, which can be prevented by 12-months of structured ExT.