BACKGROUND: Cancer treatment may impair physiological adaptations to exercise therapy, yet no study has directly compared exercise effects between cancer survivors and cancer-naive control subjects. OBJECTIVES: This study sought to examine the effects of aerobic exercise in anthracycline-treated long-term survivors of breast cancer (BCS) and to compare the effects to cancer-naive women. METHODS: The CAUSE (CArdiovascUlar Survivors Exercise) trial was a 2-arm randomized controlled trial in which long-term BCS were assigned to thrice-weekly nonlinear aerobic exercise for 5 months (BCS exercise) or usual care (BCS usual care). A third group of similarly aged cancer-naive women completed the same exercise intervention. The primary outcome was cardiorespiratory fitness (CRF) (measured as VO2peak). Secondary outcomes included cardiovascular risk factors (cardiometabolic biomarkers and body composition) and patient-reported outcomes (subjective vitality and life satisfaction). RESULTS: Between October 2020 and February 2023, 140 BCS (aged 59.0 +/- 6.4 years; 11 +/- 1 years after treatment) and 69 cancer-naive women (aged 57.8 +/- 4.9 years) were enrolled. From baseline to post-exercise intervention, VO2peak increased by 1.2 +/- 2.6 mL/kg-1/min-1 in the BCS exercise, by 0.01 +/- 2.5 mL/kg-1/min-1 in the BCS usual care group (mean difference 1.3; 95% confidence interval (CI) 0.5 to 2.1; p = 0.002), and by 2.6 +/- 2.5 mL/kg-1/min-1 in non-cancer subjects (BCS exercise versus non-cancer subjects: mean difference -1.4; 95% CI -2.2 to -0.5; p = 0.003). No changes in cardiovascular risk factors were observed. Compared with BCS usual care, the BCS exercise group reported improved subjective vitality (mean difference 2.56; 95% CI 1.22 to 3.90; p < 0.001) and satisfaction with life (mean difference 1.68; 95% CI 0.43 to 2.93; p = 0.009). CONCLUSIONS: Although aerobic exercise improves CRF in anthracycline-treated long-term BCS, the response was less than one-half that observed in cancer-naive subjects.

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