TY - JOUR
T1 - Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer
T2 - a randomized controlled trial (PAM study)
AU - Koevoets, E.W.
AU - Schagen, S.B.
AU - de Ruiter, M.B.
AU - Geerlings, M.I.
AU - Witlox, L.
AU - van der Wall, E.
AU - Stuiver, M.M.
AU - Sonke, G.S.
AU - Velthuis, M.J.
AU - Jobsen, J.J.
AU - Menke-Pluijmers, M.B.E.
AU - Göker, E.
AU - van der Pol, C.C.
AU - Bos, M.E.M.M.
AU - Tick, L.W.
AU - van Holsteijn, N.A.
AU - van der Palen, J.
AU - May, A.M.
AU - Monninkhof, E M.
AU - Haringhuizen, Annebeth W.
AU - van der Steeg, Wim A.
AU - Sommeijer, Dirkje W.
AU - Terheggen, Frederiek
AU - Blanken-Peeters, Charlotte
AU - Fliervoet, Harold
AU - Schlooz-Vries, Margrethe S.
AU - Frakking, Tanja G.
AU - van Tilburg, Marc W.A.
AU - Oldenhuis, Corina
AU - Sier, Maartje F.
AU - on behalf of PAM study group
N1 - Funding Information:
We acknowledge the following departments of the UMCU who have collected and stored data: laboratory, data management, the radiology department, and the department of rehabilitation. We would like to thank our sports medicine specialists Esther Schoots and Anne-Marie Boelens-Quist for guiding the physical fitness tests. Special thanks to all participants for their continuous effort, physiotherapists and Nordic walking instructors for supervising training sessions, and all interns and research assistants, in particular Beatrix Vogelaar and Judith Meurs for their help in gathering data. Additionally, we would like to thank the members of the PAM study group: Annebeth W. Haringhuizen, Wim A. van der Steeg, Dirkje W. Sommeijer, Frederiek Terheggen, Charlotte Blanken-Peeters, Harold Fliervoet, Margrethe S Schlooz-Vries, Tanja G. Frakking, Marc W. A. van Tilburg, Corina Oldenhuis, Maartje F. Sier.
Funding Information:
This work was supported by KWF kankerbestrijding (Grant Number UU 2015–7954).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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; VO2peak), 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 VO2peak 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.
AB - 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; VO2peak), 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 VO2peak 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.
KW - Aerobic exercise
KW - Breast cancer
KW - Cancer-related cognitive impairment
KW - Cognition
KW - Cognitive complaints
KW - Exercise training
KW - Physical exercise
KW - Physical fitness
KW - Strength exercise
UR - http://www.scopus.com/inward/record.url?scp=85130840088&partnerID=8YFLogxK
U2 - 10.1186/s13058-022-01530-2
DO - 10.1186/s13058-022-01530-2
M3 - Article
C2 - 35619188
AN - SCOPUS:85130840088
SN - 1465-5411
VL - 24
JO - Breast cancer research
JF - Breast cancer research
IS - 1
M1 - 36
ER -
