Effects of Exercise Therapy Dosing Schedule on Impaired Cardiorespiratory Fitness in Patients With Primary Breast Cancer: A Randomized Controlled Trial

Abstract

Background: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40-50 minutes per session), and volume (120-160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer.

Methods: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO2peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak (mL O2·kg-1·min-1) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety.

Results: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO2peak increased 0.6±1.7 mL O2·kg-1·min-1 (P=0.05) and 0.8±1.8 mL O2·kg-1·min-1 (P=0.07) in LET and NLET, respectively, compared with attention control. Change in VO2peak ranged from -2.7 to 4.1 mL O2·kg-1·min-1 and from -3.6 to 5.1 mL O2·kg-1·min-1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO2peak responders (ie, Δ ≥1.32 mL O2·kg-1·min-1). NLET improved all patient-reported outcomes compared with attention control.

Conclusions: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01186367.

Keywords: breast neoplasms; cardiorespiratory fitness; exercise.

Figures

Figure 1.

Planned intensity and duration of each individual session (i.e., dose) as well as the schedule of treatment dose across the study intervention period for (A) linear dosing and (B) non-linear dosing. The planned prescription depicts the intensity, duration, and scheduling of sessions under the assumption that no sessions were missed or dose modified, as per protocol. All doses were individualized to each patient on the basis of the pre-randomization cardiopulmonary exercise test (CPET). In the non-linear arm, at the end of week 8 the CPET was repeated to re-prescribe exercise intensity (green bar). The intensity of each session depicted by the colored bars as a percentage of VO2peak: (1) black – 55%, (2) blue – 65%, (3) orange – 70% to 75%, (4) grey – 85%, and (5) red – >95%. Black dots depict the planned duration of each session (mins), ranging from a minimum of 20 mins/session to a maximum of 45 mins/session. VO2peak, peak oxygen consumption.

Figure 1.

Planned intensity and duration of each individual session (i.e., dose) as well as the schedule of treatment dose across the study intervention period for (A) linear dosing and (B) non-linear dosing. The planned prescription depicts the intensity, duration, and scheduling of sessions under the assumption that no sessions were missed or dose modified, as per protocol. All doses were individualized to each patient on the basis of the pre-randomization cardiopulmonary exercise test (CPET). In the non-linear arm, at the end of week 8 the CPET was repeated to re-prescribe exercise intensity (green bar). The intensity of each session depicted by the colored bars as a percentage of VO2peak: (1) black – 55%, (2) blue – 65%, (3) orange – 70% to 75%, (4) grey – 85%, and (5) red – >95%. Black dots depict the planned duration of each session (mins), ranging from a minimum of 20 mins/session to a maximum of 45 mins/session. VO2peak, peak oxygen consumption.

Figure 2.

CONSORT Flow for Non-Pharmacological Trials.

Figure 3.

Waterfall plots for change in VO2peak. The technical error (TE) for VO2peak (Δ1.32 mL O2·kg−1·min−1) is illustrated by the shaded area. Patients with a change in VO2peak greater than TE classified as responders. Black bars: attention control; grey bars: standard linear exercise training; blue bars: non-linear exercise training. VO2peak, peak oxygen consumption.