Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
Breast Cancer Research, vol. 24, pp. 36
Abstract
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 .
Authors 30
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Utrecht University · The Netherlands Cancer Institute · University Medical Center Utrecht
Affiliation as printed
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
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The Netherlands Cancer Institute · University of Amsterdam
Affiliation as printed
Brain and Cognition Group, University of Amsterdam, Amsterdam, The Netherlands
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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The Netherlands Cancer Institute
Affiliation as printed
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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The Netherlands Cancer Institute · Amsterdam University of Applied Sciences
Affiliation as printed
Center for Quality of Life, Netherlands Cancer Institute, Amsterdam, The Netherlands
Center of Expertise Urban Vitality, Faculty of Health, University of Applied Sciences, Amsterdam, The Netherlands
Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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The Netherlands Cancer Institute
Affiliation as printed
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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Netherlands Comprehensive Cancer Organisation
Affiliation as printed
Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
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Affiliation as printed
Medical School Twente, Medisch Spectrum Twente, Enschede, The Netherlands
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Affiliation as printed
Breast Clinic, Albert Schweitzer Hospital, Dordrecht, The Netherlands
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Affiliation as printed
Department of Medical Oncology, Alexander Monro Hospital, Bilthoven, The Netherlands
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Affiliation as printed
Department of Surgery, Alrijne Ziekenhuis, Leiderdorp, The Netherlands
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Affiliation as printed
Department of Medical Oncology, ErasmusMC Cancer Institute, Rotterdam, The Netherlands
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Affiliation as printed
Department of Internal Medicine, Máxima Medisch Centrum, Eindhoven, The Netherlands
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Affiliation as printed
Breast Cancer Center, Reinier de Graaf Hospital, Delft, The Netherlands
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Medisch Spectrum Twente · University of Twente
Affiliation as printed
Department of Research Methodology, Measurement, Universiteit Twente, Enschede, The Netherlands
Medical School Twente, Medisch Spectrum Twente, Enschede, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
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Evelyn M. Monninkhof corresponding
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. E.Monninkhof@umcutrecht.nl
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
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