JACC Adv. 2026 Feb 23:102610. doi: 10.1016/j.jacadv.2026.102610. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
OBJECTIVES: 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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
PMID:41854565 | DOI:10.1016/j.jacadv.2026.102610