Impact of exercise therapy in patients undergoing breast cancer treatment

Abstract (1. publication) 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. Abstract (2. publication) Aim Muscle strength has been associated with a decreased mortality risk and reduced side-effects in oncologic patients. However, little is known about how muscle strength is affected by cancer therapy. We investigated muscle strength in breast cancer patients during treatment and also compared it with healthy individuals. Methods Breast cancer patients (N=255), staged 0-III, aged 54.4±9.4 years, were categorized into four groups according to their treatment status. Their muscle function was assessed with gold standard method by maximal isokinetic peak torque (MIPT) (60°/s, 180°/s) and maximal voluntary isometric contraction (MVIC) tests in lower and upper extremity muscle groups. Additionally, muscular fatigue index (FI%) and shoulder flexibility was evaluated. Healthy women (N=26), aged 53.3±9.8 were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on muscle function with adjustment for various clinical and socio-demographic factors. Results Consistently lower muscle strength and higher FI% was measured in knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12-16% in upper extremities in MVIC and MIPT during cancer treatment compared to healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. No serious adverse events were reported. Conclusions Patients showed markedly impaired muscle strength after adjuvant therapy. The clinically relevant decrease underlines the need of exercise therapy as early as possible in order to prevent or counteract the loss of muscle function. Abstract (3. publication) Purpose Cancer survivors are recommended to perform 150 min/week of moderate or 75 min/week of vigorous aerobic exercise, but it remains unclear how moderate and vigorous intensities can be prescribed. Therefore, it was investigated whether and how intensity prescriptions for healthy adults by the American College of Sports Medicine (ACSM) need to be adapted for breast cancer survivors. Methods 52 breast cancer survivors (stage 0-III, age 52±9 years, BMI 25.4±3.5 kg/m2) performed cardiopulmonary exercise tests at the end of primary-therapy. Intensity classes defined as percentages of maximal heart rate (HRmax), heart rate reserve (HRR), and maximal oxygen uptake (VO2max) were compared to the ACSM’s intensity classes using oxygen uptake reserve as reference. Results The prescriptions for moderate and vigorous exercise intensities were significantly different between breast cancer survivors and healthy adults when using VO2max (moderate 50–66 vs. 46–63 and vigorous 67–91 vs. 64–90 %VO2max) or HRR (moderate 26–50 vs. 40–59 and vigorous 51–88 vs. 60–89 %HRR), but not when using HRmax (moderate 65–76 vs. 64–76 and vigorous 77–94 vs. 77–95 %HRmax). Conclusions In breast cancer survivors, intensity prescriptions for healthy adults result in considerably too intense training if HRR is used as guiding factor. Prescriptions using VO2max result in a slightly too low exercise intensity, whereas recommendations in percentages of HRmax appear valid. Abstract (4. publication) Background Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer 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 breast cancer stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (2 times/week). Both interventions were group-based. The primary endpoint 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 were high. In intention-to-treat analyses for the N=155 patients, significant between-group mean differences (MD) favoring the exercise group were observed for general fatigue (P=0.044), especially for the subscale physical fatigue (MD= -0.8; 95% confidence interval = (-1.5, -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 to relaxation controls. Future perspective improved significantly stronger in the relaxation control group compared to the exercise 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 breast cancer patients during adjuvant radiotherapy. As exercise was compared to 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 to usual care can be assumed to be higher.