Abstract P4-08-01: Effects of exercise during adjuvant chemotherapy on clinical outcomes in early stage breast cancer
Authors: Courneya KS , Segal RJ , McKenzie DC , Dong H , Gelmon K , Friedenreich CM , Yasui Y , Reid RD , Crawford JJ , Mackey JR 
Published: August 2014

Abstract
Background: Observational studies suggest that physical activity following a diagnosis of breast cancer may be associated with a lower risk of recurrence and death. Some studies also suggest possible effect modification by disease stage, body mass index, and receptor status. To date, however, there are no randomized trials examining the effects of exercise on disease outcomes in any cancer patient group. Here, we report an exploratory follow-up of disease outcomes from the Supervised Trial of Aerobic versus Resistance Training (START). Patients and Methods: The START Trial was a Canadian multicenter trial that randomized 242 breast cancer patients starting adjuvant chemotherapy to either usual care (n = 82) or supervised aerobic (n = 78) or resistance (n = 82) exercise for the duration of their chemotherapy. The primary efficacy endpoint for this exploratory analysis was disease-free survival (DFS). Secondary endpoints were overall survival (OS), distant disease-free survival (DDFS), and recurrence-free interval (RFI). The two exercise arms were combined for the analysis (n = 160) and selected subgroups were explored. Results: After a median follow-up of 89 months (IQR 81 to 96), there were 25/160 (15.6%) DFS events in the exercise groups and 18/82 (22.0%) in the control group (log-rank p = 0.21). Eight-year DFS was 82.7% for the exercise groups compared with 75.6% for the control group (Hazard ratio [HR] = 0.68, 95% CI = 0.37-1.24). There were 13/160 (8.1%) deaths in the exercise groups and 11/82 (13.4%) in the control group (log-rank p = 0.21). Eight-year OS was 91.2% in the exercise groups compared with 82.7% in the control group (HR = 0.60, 95% CI = 0.27 to 1.33. There were 20/160 (12.5%) DDFS events in the exercise groups and 16/82 (19.5%) in the control group (log-rank p = 0.15). Eight-year DDFS was 86.7% in the exercise groups compared with 78.3% in the control group (HR = 0.62, 95% CI = 0.32 to 1.19). Finally, there were 20/160 (12.5%) RFI events in the exercise groups and 17/82 (20.7%) in the control group (Gray's p = 0.095). Eight-year cumulative incidence of RFI was 12.6% in the exercise groups compared with 21.6% in the control group (HR = 0.58, 95% CI = 0.30 to 1.11). Subgroup analyses for DFS and RFI suggested stronger effects for women who were overweight/obese, had stage II/III cancer, receptor positive tumors, HER2 positive tumors, received taxane-based chemotherapies, and received at least 85% of their intended chemotherapy dose-intensity. The most notable subgroup effect was for patients who received optimal chemotherapy dosing with a borderline significant effect for DFS (HR = 0.50, 95% CI = 0.25 to 1.01) and a significant effect for RFI (HR = 0.38, 95% CI = 0.18 to 0.81). Conclusions: In this exploratory follow-up of the START Trial, there was a suggestion that exercise during adjuvant chemotherapy may improve several efficacy endpoints although none achieved statistical significance. Nevertheless, the magnitude of the effects appear to be meaningful with absolute 8-year survival differences between 7% and 9% and relative rate reductions between 30% and 40%. The START Trial provides the first randomized data to suggest that adding exercise to standard chemotherapy for breast cancer may improve outcomes. A definitive phase III trial is warranted.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-08-01.