Oliver Klassen

Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life

BACKGROUND Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention. PATIENTS AND METHODS One hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. RESULTS Adherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047). CONCLUSIONS The 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the clinically relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher. TRIAL REGISTRATION ClinicalTrials.gov NCT01468766.

Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: The BEST study

BackgroundCancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce.Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood.In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy.Methods/designThe BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed.DiscussionThe BEST study is the first randomized controlled trial comparing progressive resistance training with muscle relaxation training in breast cancer patients during adjuvant radiotherapy. Based on the analysis of physiological, immunological and inflammatory parameters it will contribute to a better understanding of the physiological and psychosocial effects and the biological mechanisms of resistance training. The ultimate goal is the implementation of optimized intervention programs to reduce fatigue, improve quality of life and potentially the prognosis after breast cancer.Trial registrationClinicalTrials.gov NCT01468766

Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

PURPOSE To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. METHODS AND MATERIALS Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R(2) effect-size measures for mediation were calculated. RESULTS The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. CONCLUSIONS This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast cancer patients. This effect was counteracted by progressive resistance exercise training. Interleukin-6 and the IL-6/IL-1ra ratio seemed to mediate the beneficial effect of exercise on physical fatigue and pain but only to a small extent.

Muscle strength in breast cancer patients receiving different treatment regimes

Muscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals.

Cardiorespiratory fitness in breast cancer patients undergoing adjuvant therapy

Abstract Purpose. The aim of this work was to investigate cardiorespiratory fitness in breast cancer patients at different time points of anti-cancer treatment. Patients and methods. Non-metastatic breast cancer patients (n = 222, mean age 55 years) were categorized into four subgroups according to their treatment status. Cardiopulmonary exercise testing (CPET) was used to measure patients’ cardiorespiratory fitness, including oxygen delivery and metabolic muscle function. Testing was performed by bicycle ergometry, and maximal oxygen uptake (VO2peak) was measured. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of the O2 supply to muscle. Analysis of covariance was used to estimate the impact of different cancer treatments on cardiorespiratory fitness with adjustment for clinical factors. Results. Submaximal measures were successfully assessed in 220 (99%) and 200 (90%) patients for HR50 and VT, while criteria for maximal exercise testing were met by 176 patients (79%), respectively. The mean VO2peak was 20.6 ± 6.7 ml/kg/min, mean VT 10.7 ± 2.9 ml/min/kg and mean HR50 112 ± 16 beats/min. Chemotherapy was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant chemotherapy compared to patients with no chemotherapy or those who just started chemotherapy regime (all p < 0.01). Patients post adjuvant chemotherapy reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5 ± 4.8 ml/kg/min). Similarly, HR50 was significantly associated with treatment. However, VT was not associated with treatment. Conclusion. Breast cancer patients have marked and significantly impaired cardiopulmonary function during and after chemotherapy. Hereby, chemotherapy appears to impair cardiorespiratory fitness by influencing the oxygen delivery system rather than impacting metabolic muscle function. Our findings underline the need of exercise training in breast cancer patients to counteract the loss of cardiorespiratory fitness during the anti-cancer treatment.

Effects of 12-week resistance training during radiotherapy in breast cancer patients.

Exercise is considered to be an effective supportive treatment approach in breast cancer (BC) patients. We conducted a randomized controlled trial to assess the efficacy of a 12‐week PRT during radiotherapy. Strength performance was assessed by maximal isokinetic peak torque (MIPT) in two different angular velocities (60°/s and 180°/s) and maximal voluntary isometric contraction for shoulder external and internal rotation, as well as for knee extension and flexion were assessed pre‐ and post‐intervention in 146 patients randomized to PRT or a control group. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. Intention‐to‐treat analyses showed significant between‐group differences favoring the exercise group (EX) for MIPT in knee flexion and shoulder internal and external rotation (P < 0.05). Subgroup analyses showed borderline significant differences with regard to pretreatment history, revealing that pretreated chemotherapy patients tend to benefit more from PRT than patients without chemotherapy (P = 0.06). Strength gain at the operated arm was significantly higher than at the non‐operated arm in EX. PRT was efficacious in increasing upper and lower limb strength in BC patients undergoing adjuvant radiotherapy. Patients with restrictions due to breast cancer‐related surgery and pretreated with chemotherapy might benefit the most.