Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.

To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.

Reallocating sedentary time to physical activity: effects on fatigue and quality of life in patients with breast cancer in the Phys-Can project.

PURPOSE: We aimed to investigate the effects of reallocating sedentary time to an equal amount of light (LPA) or moderate-to-vigorous intensity physical activity (MVPA) on cancer-related fatigue and health-related quality of life (HRQoL) in patients with breast cancer. We also aimed to determine the daily amount of sedentary time needed to be reallocated to LPA or MVPA to produce minimal clinically important changes in these outcomes. METHODS: Pooled baseline data from three studies were used, including women with breast cancer who participated in the Phys-Can project. Fatigue was assessed with the Multidimensional Fatigue Inventory questionnaire (MFI; five dimensions, 4-20 scale) and HRQoL with the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30; 0-100 scale). Sedentary time and physical activity were measured with accelerometry. Isotemporal substitution modelling was used for the analyses. RESULTS: Overall, 436 participants (mean age 56 years, fatigue 11 [MFI], HRQoL 66 [EORTC QLQ-C30], LPA 254 min/day, MVPA 71 min/day) were included. Fatigue significantly decreased in two MFI dimensions when reallocating 30 min/day of sedentary time to LPA: reduced motivation and reduced activity (ß = - 0.21). Fatigue significantly decreased in three MFI dimensions when reallocating 30 min/day of sedentary time to MVPA: general fatigue (ß = - 0.34), physical fatigue (ß = - 0.47) and reduced activity (ß = - 0.48). To produce minimal clinically important changes in fatigue (- 2 points on MFI), the amount of sedentary time needed to be reallocated to LPA was ≈290 min/day and to MVPA was ≥ 125 min/day. No significant effects were observed on HRQoL when reallocating sedentary time to LPA or MVPA. CONCLUSIONS: Our results suggest that reallocating sedentary time to LPA or MVPA has beneficial effects on cancer-related fatigue in patients with breast cancer, with MVPA having the greatest impact. In relatively healthy and physically active breast cancer populations, a large amount of time reallocation is needed to produce clinically important changes. Future studies are warranted to evaluate such effects in broader cancer populations. TRIAL REGISTRATION: NCT02473003 (10/10/2014) and NCT04586517 (14/10/2020).

Effect of self-regulatory behaviour change techniques and predictors of physical activity maintenance in cancer survivors: a 12-month follow-up of the Phys-Can RCT.

BACKGROUND: Current knowledge about the promotion of long-term physical activity (PA) maintenance in cancer survivors is limited. The aims of this study were to 1) determine the effect of self-regulatory BCTs on long-term PA maintenance, and 2) identify predictors of long-term PA maintenance in cancer survivors 12 months after participating in a six-month exercise intervention during cancer treatment. METHODS: In a multicentre study with a 2 × 2 factorial design, the Phys-Can RCT, 577 participants with curable breast, colorectal or prostate cancer and starting their cancer treatment, were randomized to high intensity exercise with or without self-regulatory behaviour change techniques (BCTs; e.g. goal-setting and self-monitoring) or low-to-moderate intensity exercise with or without self-regulatory BCTs. Participants' level of PA was assessed at the end of the exercise intervention and 12 months later (i.e. 12-month follow-up), using a PA monitor and a PA diary. Participants were categorized as either maintainers (change in minutes/week of aerobic PA ≥ 0 and/or change in number of sessions/week of resistance training ≥0) or non-maintainers. Data on potential predictors were collected at baseline and at the end of the exercise intervention. Multiple logistic regression analyses were performed to answer both research questions. RESULTS: A total of 301 participants (52%) completed the data assessments. A main effect of BCTs on PA maintenance was found (OR = 1.80, 95%CI [1.05-3.08]) at 12-month follow-up. Participants reporting higher health-related quality-of-life (HRQoL) (OR = 1.03, 95%CI [1.00-1.06] and higher exercise motivation (OR = 1.02, 95%CI [1.00-1.04]) at baseline were more likely to maintain PA levels at 12-month follow-up. Participants with higher exercise expectations (OR = 0.88, 95%CI [0.78-0.99]) and a history of tobacco use at baseline (OR = 0.43, 95%CI [0.21-0.86]) were less likely to maintain PA levels at 12-month follow-up. Finally, participants with greater BMI increases over the course of the exercise intervention (OR = 0.63, 95%CI [0.44-0.90]) were less likely to maintain their PA levels at 12-month follow-up. CONCLUSIONS: Self-regulatory BCTs improved PA maintenance at 12-month follow-up and can be recommended to cancer survivors for long-term PA maintenance. Such support should be considered especially for patients with low HRQoL, low exercise motivation, high exercise expectations or with a history of tobacco use at the start of their cancer treatment, as well as for those gaining weight during their treatment. However, more experimental studies are needed to investigate the efficacy of individual or combinations of BCTs in broader clinical populations. TRIAL REGISTRATION: NCT02473003 (10/10/2014).

Does exercise intensity matter for fatigue during (neo-)adjuvant cancer treatment? The Phys-Can randomized clinical trial.

Exercise during cancer treatment improves cancer-related fatigue (CRF), but the importance of exercise intensity for CRF is unclear. We compared the effects of high- vs low-to-moderate-intensity exercise with or without additional behavior change support (BCS) on CRF in patients undergoing (neo-)adjuvant cancer treatment. This was a multicenter, 2x2 factorial design randomized controlled trial (Clinical Trials NCT02473003) in Sweden. Participants recently diagnosed with breast (n = 457), prostate (n = 97) or colorectal (n = 23) cancer undergoing (neo-)adjuvant treatment were randomized to high intensity (n = 144), low-to-moderate intensity (n = 144), high intensity with BCS (n = 144) or low-to-moderate intensity with BCS (n = 145). The 6-month exercise intervention included supervised resistance training and home-based endurance training. CRF was assessed by Multidimensional Fatigue Inventory (MFI, five subscales score range 4-20), and Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F, score range 0-52). Multiple linear regression for main factorial effects was performed according to intention-to-treat, with post-intervention CRF as primary endpoint. Overall, 577 participants (mean age 58.7 years) were randomized. Participants randomized to high- vs low-to-moderate-intensity exercise had lower physical fatigue (MFI Physical Fatigue subscale; mean difference -1.05 [95% CI: -1.85, -0.25]), but the difference was not clinically important (ie <2). We found no differences in other CRF dimensions and no effect of additional BCS. There were few minor adverse events. For CRF, patients undergoing (neo-)adjuvant treatment for breast, prostate or colorectal cancer can safely exercise at high- or low-to-moderate intensity, according to their own preferences. Additional BCS does not provide extra benefit for CRF in supervised, well-controlled exercise interventions.

"Finding my own motivation" - A Mixed Methods Study of Exercise and Behaviour Change Support During Oncological Treatment.

BACKGROUND: Exercising during oncological treatment is beneficial but challenging for persons with cancer and may require strategies to increase motivation. Behaviour change support, including specific behaviour change techniques (BCTs), have been used to facilitate exercise in persons undergoing oncological treatment, but more detailed knowledge from an individual perspective is needed to inform clinical practice. The aims were to explore the motivational experiences of exercise combined with behaviour change support, and to describe how specific BCTs were valued among persons exercising during oncological treatment. METHODS: A mixed-methods study was conducted using semi-structured interviews (n = 18) and a questionnaire (n = 229). Participants with breast, colorectal or prostate cancer who completed or dropped out of a six-month exercise programme during oncological treatment were included. The interviews were analysed with thematic analysis and the questionnaire with descriptive statistics (median and interquartile range). RESULTS: The participants underwent a motivational process through the exercise programme. By experiencing 'Health gains and mastery', 'Learning', 'Affinity', 'Commitment', and 'Managing challenges', they found incentives that fostered feelings of autonomy, competence and relatedness, leading to an increased motivation to exercise. Social support from coaches, structuring the physical environment with scheduled sessions, self-monitoring with resistance training log, and feedback based on heart rate monitor and fitness tests were the most valued BCTs. CONCLUSIONS: The results indicate the importance of finding incentives and creating an environment that fosters autonomy, competence and relatedness to motivate persons to exercise during oncological treatment. Some BCTs appear particularly useful and may be used by health professionals to increase patients' motivation to exercise.

Does inflammation markers or treatment type moderate exercise intensity effects on changes in muscle strength in cancer survivors participating in a 6-month combined resistance- and endurance exercise program? Results from the Phys-Can trial.

BACKGROUND: Resistance exercise has a beneficial impact on physical function for patients receiving oncological treatment. However, there is an inter-individual variation in the response to exercise and the tolerability to high-intensity exercise. Identifying potential moderating factors, such as inflammation and treatment type, for changes in muscle strength is important to improve the effectiveness of exercise programs. Therefore, we aimed to investigate if inflammation and type of oncological treatment moderate the effects of exercise intensity (high vs. low-moderate) on muscular strength changes in patients with breast (BRCA) or prostate cancer (PRCA). METHODS: Participants with BRCA (n = 286) and PRCA (n = 65) from the Physical training and Cancer study (Phys-Can) were included in the present study. Participants performed a combined resistance- and endurance exercise program during six months, at either high or low-moderate intensity. Separate regression models were estimated for each cancer type, with and without interaction terms. Moderators included in the models were treatment type (i.e., neo/adjuvant chemotherapy-yes/no for BRCA, adjuvant androgen deprivation therapy (ADT)-yes/no for PRCA)), and inflammation (interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα)) at follow-up. RESULTS: For BRCA, neither IL6 (b = 2.469, 95% CI [- 7.614, 12.552]) nor TNFα (b = 0.036, 95% CI [- 6.345, 6.418]) levels moderated the effect of exercise intensity on muscle strength change. The same was observed for chemotherapy treatment (b = 4.893, 95% CI [- 2.938, 12.724]). Similarly, for PRCA, the effect of exercise intensity on muscle strength change was not moderated by IL6 (b = - 1.423, 95% CI [- 17.894, 15.048]) and TNFα (b = - 1.905, 95% CI [- 8.542, 4.732]) levels, nor by ADT (b = - 0.180, 95% CI [- 11.201, 10.841]). CONCLUSIONS: The effect of exercise intensity on muscle strength is not moderated by TNFα, IL6, neo/adjuvant chemotherapy, or ADT, and therefore cannot explain any intra-variation of training response regarding exercise intensity (e.g., strength gain) for BRCA or PRCA in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02473003.

The Role of Long-Term Physical Activity in Relation to Cancer-Related Health Outcomes: A 12-Month Follow-up of the Phys-Can RCT.

PURPOSE: While moderate-to-vigorous intensity physical activity (MVPA) is associated with various health improvements shortly after completion of exercise interventions, it remains unclear which health benefits can be expected when MVPA levels are maintained in the long term in cancer survivors. We aimed to assess the associations of (1) MVPA level at 12-month follow-up and (2) long-term MVPA patterns (from immediately post-intervention to 12-month follow-up) with different cancer-related health outcomes. METHODS: In the Physical training and Cancer (Phys-Can) RCT, 577 participants diagnosed with breast (78%), prostate (19%), or colorectal (3%) cancer were randomized to 6 months of exercise during curative cancer treatment. Accelerometer-assessed physical activity and outcome data (ie, cancer-related fatigue, health-related quality of life [HRQoL], anxiety and depression, functioning in daily life, cardiorespiratory fitness, sedentary time and sleep) were collected immediately post-intervention and at 12-month follow-up. Based on the sample's median of MVPA immediately post-intervention (65 minutes/day) and the changes between the 2 measurement points, 4 categories with different long-term MVPA patterns were created: High & Increasing, High & Decreasing, Low & Increasing, and Low & Decreasing. Multiple linear regression analyses were performed for the analyses. RESULTS: A total of 353 participants were included in the analyses. At 12-month follow-up, a higher MVPA level was significantly associated with lower fatigue in 3 domains (general fatigue [ß = -.33], physical fatigue [ß = -.53] and reduced activity [ß = -.37]), higher cardiorespiratory fitness (ß = .34) and less sedentary time (ß = -.35). For long-term MVPA patterns, compared to the participants in the "Low & Decreasing" category, those in the "High & Increasing" category reported significantly lower fatigue in 3 domains (general fatigue [ß = -1.77], physical fatigue [ß = -3.36] and reduced activity [ß = -1.58]), higher HRQoL (ß = 6.84) and had less sedentary time (ß = -1.23). CONCLUSION: Our results suggest that long-term physical activity is essential for improving health outcomes post-intervention in cancer survivors. Cancer survivors, including those who reach recommended MVPA levels, should be encouraged to maintain or increase MVPA post-intervention for additional health benefits. TRIAL REGISTRATION: NCT02473003 (10/10/2014).

Patterns and determinants of adherence to resistance and endurance training during cancer treatment in the Phys-Can RCT.

BACKGROUND: Knowledge regarding adherence is necessary to improve the specificity of exercise interventions during cancer treatment. We aimed to determine adherence to resistance and endurance training interventions in parallel; identify subgroups with similar adherence characteristics; and examine determinants of these subgroups. METHODS: In the Phys-Can randomised controlled trial, participants (n = 577, 81% women, mean(SD) age 59(12) years, and 50% with BMI ≥ 25 kg/m2) starting (neo-) adjuvant treatment for breast, colorectal or prostate cancer were randomized to 6-month of high (HI) or low-to-moderate intensity (LMI) supervised, group-based resistance training and individual home-based endurance training, with or without behavior change support. Adherence was calculated as performed exercise volume as a proportion of prescribed exercise volume (0-100%), overall (HI and LMI groups) and for frequency, intensity, type and time (FITT principles) (HI group). Adherence to resistance training was plotted against adherence to endurance training overall and for each FITT principle. K-means cluster analysis was used to identify subgroups with similar adherence characteristics. Potential determinants of subgroup membership were examined using multinomial logistic regression. RESULTS: We found a positive curvilinear correlation between adherence to resistance and endurance training overall. A similar correlation was seen for adherence to frequency of resistance vs. endurance training in the HI group. In the HI group, adherence to resistance training intensity and time was > 80% for almost all participants. For endurance training adherence ranged from 0 to 100% for each of the FITT principles. Three clusters were identified, representing low, mixed, and high adherence to resistance and endurance training overall. Participants with higher age (Relative risk ratio [95% CI]; LMI: 0.86[0.77-0.96], HI: 0.83[0.74-0.93]), no behaviour change support (LMI: 0.11[0.02-0.56], HI: 0.20[0.05-0.85]), higher cardiorespiratory fitness (LMI: 0.81[0.69-0.94], HI: 0.80[0.69-0.92]), more fatigue (according to the reduced activity subscale of the MFI questionnaire) (LMI: 0.48[0.31-0.73], HI: 0.69[0.52-0.93]) or higher quality of life (LMI: 0.95[0.90-1.00], HI: 0.93[0.88-0.98]) were less likely to be in the low than the high adherence cluster whether randomised to LMI or HI training. Other determinants were specific to those randomised to LMI or HI training. CONCLUSIONS: In an exercise intervention during cancer treatment, adherence to resistance and endurance training were positively correlated. Personalisation of interventions and additional support for some subgroups of participants may improve adherence. Trial registration NCT02473003 (clinicaltrials.gov, Registered 16/06/2015).

Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment.

Exercise training has been hypothesized to lower the inflammatory burden for patients with cancer, but the role of exercise intensity is unknown. To this end, we compared the effects of high-intensity (HI) and low-to-moderate intensity (LMI) exercise on markers of inflammation in patients with curable breast, prostate and colorectal cancer undergoing primary adjuvant cancer treatment in a secondary analysis of the Phys-Can randomized trial (NCT02473003). Sub-group analyses focused on patients with breast cancer undergoing chemotherapy. Patients performed 6 months of combined aerobic and resistance exercise on either HI or LMI during and after primary adjuvant cancer treatment. Plasma taken at baseline, immediately post-treatment and post-intervention was analyzed for levels of interleukin 1 beta (IL1B), IL6, IL8, IL10, tumor-necrosis factor alpha (TNFA) and C-reactive protein (CRP). Intention-to-treat analyses of 394 participants revealed no significant between-group differences. Regardless of exercise intensity, significant increases of IL6, IL8, IL10 and TNFA post-treatment followed by significant declines, except for IL8, until post-intervention were observed with no difference for CRP or IL1B. Subgroup analyses of 154 patients with breast cancer undergoing chemotherapy revealed that CRP (estimated mean difference (95% CI): 0.59 (0.33; 1.06); P = 0.101) and TNFA (EMD (95% CI): 0.88 (0.77; 1); P = 0.053) increased less with HI exercise post-treatment compared to LMI. Exploratory cytokine co-regulation analysis revealed no difference between the groups. In patients with breast cancer undergoing chemotherapy, HI exercise resulted in a lesser increase of CRP and TNFA immediately post-treatment compared to LMI, potentially protecting against chemotherapy-related inflammation.

Exercise Adherence and Effect of Self-Regulatory Behavior Change Techniques in Patients Undergoing Curative Cancer Treatment: Secondary Analysis from the Phys-Can Randomized Controlled Trial.

INTRODUCTION: Adherence to exercise interventions in patients with cancer is often poorly described. Further, it is unclear if self-regulatory behavior change techniques (BCTs) can improve exercise adherence in cancer populations. We aimed to (1) describe exercise adherence in terms of frequency, intensity, time, type (FITT-principles) and dropouts, and (2) determine the effect of specific self-regulatory BCTs on exercise adherence in patients participating in an exercise intervention during curative cancer treatment. METHODS: This study was a secondary analysis using data from a Swedish multicentre RCT. In a 2×2 factorial design, 577 participants recently diagnosed with curable breast, colorectal or prostate cancer were randomized to 6 months of high (HI) or low-to-moderate intensity (LMI) exercise, with or without self-regulatory BCTs (e.g., goal-setting and self-monitoring). The exercise program included supervised group-based resistance training and home-based endurance training. Exercise adherence (performed training/prescribed training) was assessed using attendance records, training logs and heart rate monitors, and is presented descriptively. Linear regression and logistic regression were used to assess the effect of self-regulatory BCTs on each FITT-principle and dropout rates, according to intention-to-treat. RESULTS: For resistance training (groups with vs without self-regulatory BCTs), participants attended on average 52% vs 53% of prescribed sessions, performed 79% vs 76% of prescribed intensity, and 80% vs 77% of prescribed time. They adhered to exercise type in 71% vs 68% of attended sessions. For endurance training (groups with vs without self-regulatory BCTs), participants performed on average 47% vs 51% of prescribed sessions, 57% vs 62% of prescribed intensity, and 71% vs 72% of prescribed time. They adhered to exercise type in 79% vs 78% of performed sessions. Dropout rates (groups with vs without self-regulatory BCTs) were 29% vs 28%. The regression analysis revealed no effect of the self-regulatory BCTs on exercise adherence. CONCLUSION: An exercise adherence rate ≥50% for each FITT-principle and dropout rates at ~30% can be expected among patients taking part in long-term exercise interventions, combining resistance and endurance training during curative cancer treatment. Our results indicate that self-regulatory BCTs do not improve exercise adherence in interventions that provide evidence-based support to all participants (e.g., supervised group sessions). TRIAL REGISTRATION: NCT02473003.

Comparison between logbook-reported and objectively-assessed physical activity and sedentary time in breast cancer patients: an agreement study.

BACKGROUND: Increasing physical activity (PA) and decreasing sedentary time (ST) have important health effects among breast cancer patients, a growing population group. PA and sedentary behaviors are complex multi-dimensional behaviors and are challenging to monitor accurately. To date few studies have compared self-reports and objective measurement in assessing PA and ST in women undergoing breast cancer treatments. The aim of the present study was to compare self-reports and objective measures for assessing daily time spent in moderate-intensity physical activity (MPA), vigorous-intensity physical activity (VPA) and ST in women undergoing breast cancer treatments. METHODS: Baseline data from 65 women with breast cancer scheduled to undergo adjuvant treatment was included. Daily time spent in MPA, VPA and ST was assessed by a study-specific logbook and the SenseWear Armband mini (SWA). The level of agreement between the two measurement methods was then determined by performing Bland-Altman plots with limits of agreements, and calculating Spearman's rank correlation coefficients. RESULTS: The mean difference between the logbook and SWA with limits of agreement was 14 (±102) minutes for MPA, 1 (±21) minute for VPA and -196 (±408) minutes for ST, respectively. The logbook reported an average of 34 and 50% higher values than the SWA for MPA and VPA, as well as an average of 27% lower values for ST (P < 0.05). The Spearman's rank correlation coefficients showed that the differences between the methods increased as the average amount of time spent in PA and ST increased (P < 0.01). CONCLUSIONS: The results imply that the two measurement methods have limited agreement and cannot be used interchangeably.