Effects of Non-Linear or Linear Aerobic Training (AT) Dosing Regimens on Impaired Cardiovascular (CV) Function in Patients with Operable Breast Cancer: A Randomized Controlled Trial (RCT).

Abstract

541 Background: Breast cancer therapy causes marked impairments in CV function predisposing to elevated risk of CV morbidity. We investigated the effects of two AT dosing regimens on CV function in post-treatment patients with operable breast cancer. Methods: In a three-arm, parallel-group RCT, 174 post-menopausal patients (2.8 years post primary adjuvant therapy) with impaired age/sex-matched peak oxygen consumption (VO2peak) were randomized to: (1) conventional linear AT (uniform dose-intensity / session), (2) nonlinear AT (variable dose-intensity / session), or (3) stretching (attention control). AT consisted of 64 supervised treadmill walking sessions delivered four times weekly at either ~70% VO2peak for 40 mins/session (linear) or 55% to 100% VO2peak for 20-45 mins/session (nonlinear) for 16 consecutive weeks. Stretching was matched to AT on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak. Secondary end points were other markers of CV risk profile (biochemical CV risk profile, cardiac function, body composition), patient-reported outcomes (PROs), tolerability (e.g., relative dose intensity), and safety. All analyses followed the intention-to-treat principle. Results: Rates of lost-to-follow were < 10% in all arms. Relative dose intensity of AT was 73% ± 27% and 80% ± 21% in linear and nonlinear arms, respectively. No serious adverse events were observed. In adjusted analysis, compared to control, VO2peak (ml O2.kg-1.min-1) increased 0.7 (± 0.3) ml O2.kg-1.min-1 (p = 0.06) and 0.8 (± 0.4) ml O2.kg-1.min-1 (p = 0.02) in linear and nonlinear AT, respectively. Rates of VO2peak improvement greater than the technical error of measurement (i.e., ≥1.32ml O2.kg-1.min-1) were 33% and 39% in linear and nonlinear AT (p = 0.03), respectively. Both AT regimens were associated with improvements in several secondary CV end points but only nonlinear AT improved PROs compared with control (all p’s < 0.05). There were no differences between the two AT regimens. Conclusion: AT significantly improves CV function and PROs in post-treatment breast cancer patients. The efficacy-tolerability ratio favors the non-linear regimen over the conventional linear prescription approach. Clinical trial information: NCT01186367.