Cardiorespiratory fitness is an independent risk factor for cardiovascular disease and shortened life expectancy in breast cancer survivors. This randomised controlled trial (n = 153) was designed for patients with a physically inactive lifestyle prediagnosis and concurrently referred to adjuvant chemotherapy. We compared two 12-week exercise interventions aimed at physiological and patientreported outcomes (cardiorespiratory fitness, muscle strength, metabolic markers, physical activity, pain, fatigue), including a 39-week follow-up. A supervised hospital-based moderate to high intensity group exercise intervention was compared to an instructed home-based individual pedometer intervention. The two 12-week interventions included oncologists' recommendations and systematic health counselling. Outcomes were measured at baseline and week 6, 12 and 39. Primary outcome cardiorespiratory fitness declined significantly during chemotherapy and was restored in both interventions at follow-up. The interventions effectively engaged breast cancer patients in sustaining physical activities during and following adjuvant treatment. A composite metabolic score improved significantly. Positive cardiorespiratory fitness responders had improved clinical effects on fatigue, pain and dyspnoea versus negative responders. We conclude that a loss of cardiorespiratory fitness among physically inactive breast cancer patients may be restored by early initiated interventions and by adapting to physical activity recommendations, leading to a decreased cardiovascular risk profile in breast cancer survivors. Physical inactivity and sedentary behaviour represent a challenge for global health due to a significant risk of premature death from chronic diseases such as cardiovascular diseases, diabetes and cancer 1,2. In breast cancer (BC), physical inactivity and obesity has consistently been associated with an increased risk of recurrence 3,4 , though physiological, biological and molecular pathways are partly known 5-8. Low cardiorespiratory fitness (CRF) increases risk for coronary heart disease and affects survival in BC survivors 9 , similar to asymptomatic women 10 , low-risk adults 11 and high-risk sedentary populations 12,13. Compared with healthy sedentary Americans, a relative 25% decline in CRF has been shown to be a primary recurring effect in the BC trajectory 14 , a finding confirmed in a German cross-sectional study 15. The causal mechanisms involved in this decline in CRF in patients with BC may be related to a cascade of factors in the oxygen delivery system 15-17. These factors may