# Effect of physical exercise on white matter microstructure in chemotherapy-treated breast cancer patients: a randomized controlled trial (PAM study)

## TL;DR

A 6-month exercise program did not improve brain white matter in breast cancer patients who had chemotherapy, but had unexpected effects in those with high fatigue.

## Contribution

The study is the first to investigate exercise effects on white matter in chemotherapy-treated breast cancer patients using DTI and TBSS.

## Key findings

- Exercise did not significantly affect whole brain or voxel-wise fractional anisotropy or mean diffusivity.
- Highly fatigued patients showed significant clusters of decreased FA in specific brain regions after the intervention.
- The observed FA decrease in fatigued patients was not predictive of cognitive changes.

## Abstract

Physical exercise is a promising intervention to improve brain white matter integrity. In the PAM study, exercise intervention effects on white matter integrity were investigated in breast cancer patients. Chemotherapy-treated breast cancer patients with cognitive problems were randomized 2–4 years post-diagnosis to an exercise (n = 91) or control group (n = 90). The 6-month exercise intervention consisted of four hours/week of aerobic and resistance training. White matter integrity was measured at baseline and 6-month follow-up with fractional anisotropy (FA) and mean diffusivity (MD), which were derived from magnetic resonance diffusion tensor imaging (DTI). Both DTI metrics were analyzed whole brain and voxel-wise with a modified tract based spatial statistics (TBSS) procedure. Other measurements included cognition and physical fitness. Exercise effects were analyzed with multiple regression analyses. An explorative analysis was conducted in highly fatigued patients. DTI scans were available for 69 patients of the intervention (age = 52.3 ± 8.9yrs.) and 72 patients of the control group (age = 53.2 ± 8.6yrs.). Whole brain and voxel-wise analyses revealed no significant intervention effects on FA and MD. In highly fatigued patients (exercise: n = 32; control: n = 24), significant clusters of decreased FA post-intervention were observed in the left inferior and superior longitudinal fasciculus. Mean FA in these clusters was not predictive of cognition. A 6-month exercise intervention did not affect white matter integrity in chemotherapy-treated breast cancer patients. However, in highly fatigued breast cancer patients a significant FA decrease was observed post-intervention. The direction of these results is unexpected, and more research is needed to further understand these results.

The online version contains supplementary material available at 10.1007/s11682-024-00965-9.