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Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors.To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors.Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group. The fitness center intervention was a structured thrice weekly aerobic (30 min brisk walking treadmill in target heart range) combined with resistance (30 min of lower body strength training) exercise program, supervised for the first 6 months. The home based group received national guidelines for 30 min moderate intensity exercise most days of the week. Fasting serum samples were collected at baseline, 6 and 12 months for insulin, glucose, lipids and hemoglobin A-1C. A graded exercise stress test was also performed at baseline and 6 months.The majority of subjects were white (85.7%), had breast cancer (83.1%) and the average age was 51.9 years. Subjects in the fitness center intervention had significantly improved time on treadmill (p = .039), improved heart rate recovery at 1 min (p = .028), greater MET minutes/week (p ≤ .0001), a trend for improved insulin resistance (p = .067) and stable insulin levels (p = .045) compared to the home based physical activity group.Exercise represents a potential cardiac risk reduction intervention for cancer survivors.NCT01102985.