# Predictors of fatigue improvement in multimodal, multimodal-aerobic and aerobic exercise intervention studies in breast cancer survivors with cancer-related fatigue

## TL;DR

This study finds that baseline autonomic regulation and internal coherence predict long-term improvement in cancer-related fatigue among breast cancer survivors after various exercise therapies.

## Contribution

The study identifies Trait aR and ICS as novel long-term predictors of CRF therapy success in breast cancer survivors.

## Key findings

- Trait aR and ICS are significant predictors of CRF improvement across multiple timepoints in the CRF-2 study.
- Cognitive function showed borderline significance only at the four-year follow-up.
- Baseline autonomic regulation and internal coherence predict therapy response in multimodal, aerobic, or combined treatments.

## Abstract

Cancer-related fatigue (CRF) is common among breast cancer (BC) survivors. In addition to aerobic training, psychoeducation, sleep education/restriction, and mindfulness-based therapies are shown to reduce CRF. This study investigates the predictive effect of hygiogenetic and salutogenetic concepts, such as autonomic regulation (aR), self-regulation (SRS) and internal coherence (ICS) along with sleep quality (PSQI) and quality of life (EORTC QLQ C30, including cognitive, emotional and physical functioning) on the success of CRF therapies. Two studies are analyzed: a pilot (CRF-1) with 36 BC patients and a follow-up study (CRF2) with 126 patients either randomized or assigned to therapy by preference. All parameters were assessed at baseline and 10 weeks post-intervention (T1), and in CRF-2 also six months later (T2), and after four years (T3). Multiple linear regression models were applied. Trait aR and ICS are shown to be significant predictors of CRF when all timepoints of the CRF-2 study are included (βTrait aR = −0.170, df = 70, p < 0.001; βICS = −0.210, df = 70, p < 0.01) as well as when combined with data of the CRF-1 study (βTrait aR = −0.144, df = 101, p = 0.001; βICS = −0.211, df = 101, p < 0.01). Cognitive Function showed a borderline significance only at T3 and when all CRF-2 study time measurements were combined (βCF = −0.073, df = 70, p < 0.05). Using data from two studies with multimodal, aerobic and combined CRF treatments, this study highlights Trait aR and ICS at baseline as long-term predictors of CRF even four years after intervention. A stable autonomic regulation including rest/activity regulation and internal coherence are predictors for therapy response of a multimodal, combination or aerobic treatment in breast cancer survivors with CRF.

The online version contains supplementary material available at 10.1038/s41598-025-06701-7.