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Open Access 01-12-2022 | Breast Cancer | Research article

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)

Authors: E. W. Koevoets, S. B. Schagen, M. B. de Ruiter, M. I. Geerlings, L. Witlox, E. van der Wall, M. M. Stuiver, G. S. Sonke, M. J. Velthuis, J. J. Jobsen, M. B. E. Menke-Pluijmers, E. Göker, C. C. van der Pol, M. E. M. M. Bos, L. W. Tick, N. A. van Holsteijn, J. van der Palen, A. M. May, E. M. Monninkhof, PAM study group

Published in: Breast Cancer Research | Issue 1/2022

Abstract

Background

Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis.

Methods

Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO_2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors.

Results

We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO_2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI − 1.2; − 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI − 52.9; − 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)].

Conclusions

A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients.

Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924.

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Title: Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
Authors: E. W. Koevoets
S. B. Schagen
M. B. de Ruiter
M. I. Geerlings
L. Witlox
E. van der Wall
M. M. Stuiver
G. S. Sonke
M. J. Velthuis
J. J. Jobsen
M. B. E. Menke-Pluijmers
E. Göker
C. C. van der Pol
M. E. M. M. Bos
L. W. Tick
N. A. van Holsteijn
J. van der Palen
A. M. May
E. M. Monninkhof
PAM study group
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Fatigue
Cytostatic Therapy
Published in: Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-022-01530-2

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