Timing of exercise therapy when initiating adjuvant chemotherapy for breast cancer: a randomized trial

Abstract

Aims: The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer.

Methods and results: Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens-concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20-50 min at 55%-100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, -0.88 mL O2·kg-1·min-1; 95% confidence interval (CI): -3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg-1·min-1, P < 0.001).

Conclusion: There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

Keywords: Aerobic training; Cardiorespiratory fitness; Exercise capacity; Treatment sequencing.

Structured Graphical Abstract

Summary of the key findings of this study. The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (VO₂peak) in cancer patients initiating adjuvant chemotherapy is not known. In this randomized controlled trial of 158 patients with primary breast cancer, concurrent (during chemotherapy only) and sequential (after chemotherapy only) had similar VO₂peak benefit. Continuous (concurrent plus sequential) exercise was the only schedule associated with significant VO₂peak improvements compared to baseline.

Figure 1

CONSORT flow for non-pharmacological trials. Definitions. Did not receive allocated intervention: Did not complete at least 1 exercise therapy session; Lost to follow-up: non-completion of the cardiopulmonary exercise test assessment at T2. COVID-19: coronavirus disease 2019.

Figure 2

Change in model-estimated marginal means of VO₂peak. Panel A: Change in VO₂peak during chemotherapy for concurrent exercise therapy and usual care (Delta 1). Panel B: Change in VO₂peak after chemotherapy for sequential exercise therapy and usual care (Delta 2). Panel C: Overall comparison (Delta 3): difference between Delta 1 and Delta 2 (i.e. difference for the change in VO₂peak between concurrent exercise therapy and usual care during chemotherapy vs. change in VO₂peak between sequential exercise therapy and usual care after chemotherapy). Error bars indicate 1 standard error. VO₂peak, peak oxygen consumption; T0; baseline; T1; immediately after last chemotherapy cycle; T2, post-intervention at ≈ 28–40 weeks post-randomization.

Figure 3

Change in model-estimated marginal means of VO₂peak from baseline to post-intervention (T0 to T2). Error bars indicate 1 standard error. VO₂peak, peak oxygen consumption; T0; baseline; T2, post-intervention at ≈ 28–40 weeks post-randomization.