Abstract P6-12-06: Effect and moderators of exercise on fatigue in patients with breast cancer: Meta-analysis of individual patient data
Authors: van Vulpen JK , Sweegers MG , Kalter J , Peeters PH , Courneya KS , Newton RU , Aaronson NK , Jacobsen PB , Steindorf K , Stuiver MM , Hayes S , Mesters I , Knoop H , Goedendorp M , Mutrie N , Thorsen L , Schmidt M , Sonke GS , Bohus M , James EL , Oldenburg HS , Velthuis MJ , Nollet F , Wenzel J , Wiskemann J , Galvão DA , Chinapaw MJ , Irwin ML , Griffith KA , van Weert E , Daley AJ , McConnachie A , Schulz K-H , Short CE , Plotnikoff RC , Potthoff K , van Beurden M , van Harten WH , Schmitz KH , Winters-Stone KM , Taaffe DR , van Mechelen W , Kersten M-J , Verdonck-de Leeuw IM , Brug J , Buffart LM , May AM 
Published: February 2018

Abstract
Background - Fatigue is one of the most common and disabling complaints in patients with breast cancer and can effectively be reduced by physical exercise, with small to moderate effect sizes. To identify heterogeneity in responses to exercise and to further personalize exercise prescriptions, moderators of exercise effects on fatigue should be investigated. However, most randomized controlled trials (RCTs) are not adequately powered for such analyses. Therefore we conducted meta-analyses using the individual patient data of several exercise RCTs. The aim is to investigate the effect and moderators of physical exercise on cancer-related fatigue in patients with breast cancer.
Methods - Within the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium, principal investigators of 34 exercise RCTs worldwide have shared their individual patient data. Twenty-two of these RCTs included patients with breast cancer with a total sample size of 3,061. Different questionnaires to assess level of fatigue were used, which was acknowledged by using z-scores in the analysis. A one-step individual patient data meta-analysis, using a linear mixed-effect model adjusted for baseline fatigue, with a random intercept on study (to account for study clustering) was undertaken to investigate effect of exercise on fatigue. The result, a between-group difference in z-scores, corresponds to a Cohen's d effect size. An interaction term was included in the model to assess potential moderators including demographic (age, marital status, education), clinical (body mass index, presence of distant metastasis), intervention-related (intervention timing, delivery mode and duration), and exercise-related (exercise type, frequency, intensity, duration) characteristics.
Results – Exercise significantly reduced fatigue reported by women with breast cancer (β= -0.15, 95% CI -0.21;-0.09). This effect did not differ significantly between patients with different demographic and clinical characteristics (p-valuesinteraction &gt;0.05). Also, neither timing (during or post-treatment) and duration of the intervention, nor exercise-related factors moderated intervention effects on fatigue. Supervised exercise had significantly larger effects on fatigue than unsupervised exercise (βdifference= -0.17, 95%CI -0.28;-0.05). Compared to the control group, supervised exercise significantly improved fatigue (β = -0.21, 95%CI = -0.28;-0.14), while unsupervised exercise did not (β = -0.04, 95%CI = -0.14;0.06).
Conclusion – Exercise significantly reduces fatigue in patients with breast cancer across subgroups formed on the basis of age, marital status, education level, body mass index, and presence of distant metastasis. The effect of exercise is significantly larger when performed under supervision. Hence, exercise, and preferably supervised exercise, represents a viable intervention for the prevention and treatment of fatigue among patients with breast cancer.
Citation Format: van Vulpen JK, Sweegers MG, Kalter J, Peeters PH, Courneya KS, Newton RU, Aaronson NK, Jacobsen PB, Steindorf K, Stuiver MM, Hayes S, Mesters I, Knoop H, Goedendorp M, Mutrie N, Thorsen L, Schmidt M, Sonke GS, Bohus M, James EL, Oldenburg HS, Velthuis MJ, Nollet F, Wenzel J, Wiskemann J, Galvão DA, Chinapaw MJ, Irwin ML, Griffith KA, van Weert E, Daley AJ, McConnachie A, Schulz K-H, Short CE, Plotnikoff RC, Potthoff K, van Beurden M, van Harten WH, Schmitz KH, Winters-Stone KM, Taaffe DR, van Mechelen W, Kersten M-J, Verdonck-de Leeuw IM, Brug J, Buffart LM, May AM. Effect and moderators of exercise on fatigue in patients with breast cancer: Meta-analysis of individual patient data [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-06.