Mechanisms Underlying Reduced Peak Oxygen Uptake in Older Long-Term Breast Cancer Survivors

Cardiotoxic breast cancer therapy is associated with acute reductions in peak oxygen uptake (VO₂) (VO₂peak) that may contribute to future heart failure. Whether impaired VO₂peak is observed in older long-term breast cancer survivors (BCS) remains unclear.

We evaluated VO₂peak and its Fick determinants in older (≥60 years) long-term female BCS previously treated with cardiotoxic therapy (n = 53; age: 69 ± 5 years; 15 ± 5 years post-therapy) and controls (CON; n = 20; age: 69 ± 5 years).

Participants underwent maximal cardiopulmonary exercise testing to quantify VO₂peak. Biventricular ejection fraction, cardiac hemodynamics (cardiac output, stroke volume [SV], and heart rate) and arteriovenous oxygen content difference (C(a-v)O₂diff) were measured at rest and during submaximal stepping exercise with real-time cardiac and oximetry-based magnetic resonance imaging. Peak calf muscle VO₂ was calculated from blood flow and C(a-v)O₂diff, assessed using phase contrast and magnetic resonance imaging oximetry at peak plantar flexion exercise.

Older BCS had lower VO₂peak than CON (-2.6 mL/kg/min, P = 0.019), and a nonsignificantly lower cardiac output augmentation during submaximal stepping exercise (Δ0.6 L/min less, P = 0.095), secondary to a blunted augmentation in SV (Δ5 mLs less, P = 0.010) and ejection fraction (left-ventricle: Δ3% less, P = 0.062; right-ventricle: Δ4% less, P = 0.025). There were no group differences in heart rate and C(a-v)O₂diff during submaximal stepping. Peak calf muscle VO₂, blood flow, and C(a-v)O₂diff were also similar between groups.

Compared to CON, older, long-term BCS display lower VO₂peak, and blunted SV during exertion. The prognostic links between VO₂peak and future cardiovascular disease suggests decreased VO₂peak may be an underappreciated risk factor in older long-term BCS.