Effects of Supervised Exercise during Neoadjuvant Chemotherapy on Tumor Response in Patients with Breast Cancer (Neo-train): A Randomized Controlled Trial

Pre-clinical studies have indicated that physical exercise may enhance chemotherapy efficacy. Clinical trials are needed to investigate this. We hypothesised that an exercise program during neoadjuvant chemotherapy (NACT) would improve tumour response in patients with breast cancer. Neo-train was a randomised controlled trial allocating patients with breast cancer to usual care (CON) or supervised high-intensity interval training and progressive resistance training three times weekly during 18-24 weeks of NACT (EX). The two groups were compared on tumour size, assessed by magnetic resonance imaging as primary outcome, and secondary clinical/pathological, biological, physical and patient-reported outcomes. From 2021 to 2023, 102 participants were randomised to the EX (n=50) or CON (n=52) group. We found no between-group differences in median tumour size change from baseline to pre-surgery (EX vs CON -3.0 millimetre [95% confidence interval (CI) -8.0 to 14.0], the proportion with radiologic complete response (EX 65% vs CON 56%, odds ratio 1.16 [95% CI 0.39 to 3.91]) or pathologic complete response (EX 59% vs CON 56%, odds ratio 1.03 [95% CI 0.43 to 2.46]). The exercise program was associated with higher relative dose intensity, fewer dose delays, shorter hospital stays, increased cardiorespiratory fitness, muscle strength, and level of physical activity. We found no differences for tumour infiltrating lymphocytes, body composition, health-related quality of life, anxiety, depression, psychological distress, or participation in rehabilitation between groups. Although the exercise program did not affect tumour size, the positive effects on chemotherapy completion and shorter hospitalisations suggest improved treatment tolerance.