High-intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines.

INTRODUCTION: Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy. METHODS: In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3 days/week for 8 weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein). RESULTS: After 8 weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p < 0.001). MetS variables (HDL-C, glucose, and triglycerides) and circulating levels of MetS-related biomarkers were significantly improved in the HIIT group compared with controls (p < 0.001). Non-significant differences were found in body composition outcomes at the end of the study. CONCLUSIONS: HIIT may be an effective strategy to improve MetS in breast cancer patients undergoing anthracycline chemotherapy. Furthermore, changes in MetS were independent of changes in body composition.

Effect of high-intensity interval training on patient-reported outcomes and physical function in women with breast cancer receiving anthracycline-based chemotherapy.

PURPOSE: The purpose of this study was to determine the effects of an 8-week HIIT intervention on patient-reported outcomes and physical function in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty breast cancer patients were recruited prior to initiating treatment and randomized into the HIIT group (n = 15) or control (CON) group (n = 15). The HIIT group attended HIIT sessions three days per week for eight weeks. The CON group was asked to maintain their current level of physical activity. Patient-reported outcomes were assessed by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), Multidimensional Fatigue Inventory with 20 questions (MFI-20), and the 15-item Five-Facet Mindfulness Questionnaire (FFMQ-15). Physical function was assessed using the timed up and go (TUG), 30-s sit-to-stand (30STS), Margaria-Kalamen stair climb test, and 6-min walk test (6MWT). Repeated measures ANCOVA and paired t-tests were performed to assess group differences. RESULTS: All patients completed the 8-week study with 82.3% adherence to the intervention among the HIIT group. Post-intervention, significant improvements were found for the Margaria-Kalamen stair climb test (- 3.39%; P = 0.013) and 6MWT (+ 11.6%; P = 0.008) in the HIIT group compared to baseline and CON group. No changes in patient-reported outcomes, TUG, and 30STS were observed following the 8-week study period in both groups (P > 0.05). CONCLUSIONS: HIIT may be an effective strategy to improve physical function and possibly maintain QOL in breast cancer patients undergoing the anthracycline-based chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

Prehabilitative Exercise for the Enhancement of Physical, Psychosocial, and Biological Outcomes Among Patients Diagnosed with Cancer.

PURPOSE OF REVIEW: This review summarizes the effects of prehabilitative exercise interventions on the physical, psychosocial, and biological outcomes among patients with cancer. Current gaps and future directions in prehabilitative exercise research will be addressed. RECENT FINDINGS: Prehabilitative exercise mitigates the detrimental impact of cancer surgery on physical fitness, noted by increases in maximal oxygen consumption and 6-min walk distance. Beneficial effects on psychosocial and biological outcomes remain inconclusive. Aerobic exercise interventions were often prescribed and included low-, moderate-, or high-intensity exercise. Resistance exercise interventions were often performed in conjunction with aerobic exercise. Prehabilitative exercise elicits robust improvements in physical fitness; however, effect on psychosocial and biological outcomes remains inconclusive. Exercise prescription parameters varied greatly by frequency, intensity, time, and type across multiple cancer diagnoses. Future investigations are needed to systematically dose exercise for a wider variety of outcome measures, with an overall goal to set forth pre-operative exercise guidelines.

Effects of supervised exercise on progression-free survival in lymphoma patients: an exploratory follow-up of the HELP Trial.

PURPOSE: Few randomized controlled trials in exercise oncology have examined survival outcomes. Here, we report an exploratory follow-up of progression-free survival (PFS) from the Healthy Exercise for Lymphoma Patients (HELP) Trial. METHODS: The HELP Trial randomized 122 lymphoma patients between 2005 and 2008 to either control (n = 62) or 12 weeks of supervised aerobic exercise (n = 60). PFS events were abstracted from medical records in 2013. In addition to the randomized comparison, we explored the effects of exercise adherence (<80 % vs. ≥80 %) and control group crossover (no vs. yes). RESULTS: After a median follow-up of 61 months (interquartile range 36-67), the adjusted 5-year PFS was 64.8 % for the exercise group compared with 65.0 % for the control group (Hazard ratio [HR] 1.01, 95 % CI 0.51-2.01, p = 0.98). In the secondary analysis, the adjusted 5-year PFS was 59.0 % in the control group without crossover compared with 69.2 % for the control group with crossover (HR 0.68, 95 % CI 0.22-2.06, p = 0.49), 67.7 % for the exercise group with <80 % adherence (HR 0.72, 95 % CI 0.28-1.85, p = 0.50), and 68.4 % for the exercise group with ≥80 % adherence (HR 0.70, 95 % CI 0.32-1.56, p = 0.39). In a post hoc analysis combining the three groups that received supervised exercise, the adjusted 5-year PFS for the supervised exercise groups was 68.5 % compared with 59.0 % for the group that received no supervised exercise (HR 0.70, 95 % CI 0.35-1.39, p = 0.31). CONCLUSIONS: This exploratory follow-up of the HELP Trial suggests that supervised aerobic exercise may be associated with improved PFS in lymphoma patients. Larger trials designed to answer this question are needed.

Resistance Exercise and Skeletal Muscle-Related Outcomes in Patients with Cancer: A Systematic Review.

BACKGROUND: Skeletal muscle loss is prevalent throughout the cancer continuum and correlated with morbidity and mortality. Resistance exercise has been trialed to mitigate skeletal muscle loss. This systematic review summarizes and qualitatively synthesizes the effects of resistance exercise on muscle-related outcomes in adult cancer populations, including skeletal muscle mass, performance and muscle-related biomarkers. METHODS: The systematic review protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched electronic databases including AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus from inception to December 2021. We included randomized controlled trials that investigated the effects of resistance exercise on muscle-related outcomes in adult cancer populations. Interventions that involved any resistance exercise were included. Muscle-related outcomes were categorized as skeletal muscle mass (e.g., lean mass, appendicular muscle mass), muscle performance (e.g., muscle strength, physical function), and muscle-related biomarkers (e.g., muscle cells, metabolic/inflammatory markers). Risk of bias (RoB) was assessed using the Cochrane ROB tool. RESULTS: A total of 102 studies from 101 randomized controlled trials were included. The majority of studies focused on breast cancer (46%) and those who completed treatment (43%). Resistance exercise interventions were largely 3-4 months long (48%), combined with aerobic exercise (56%), at a vigorous intensity (25%), and in-person/supervised settings (57%). Among the studies assessing muscle mass, performance, and biomarkers ( n = 42, 83, and 22, respectively), resistance exercise interventions improved upper/lower body or appendicular muscle mass (67%-100%), muscle strength (61%-68%), and physical function (74%-100%). Most biomarkers did not show significant changes (75%-100%) or showed inconsistent results. CONCLUSIONS: Generally, resistance exercise had positive effects on skeletal muscle mass and performance with no negative effects compared to controls. Our findings demonstrated that resistance exercise may be an effective strategy to attenuate deterioration or exert improvements in muscle mass and performance outcomes.

Efficacy of resistive exercise on skeletal muscle-related outcomes in cancer survivors: a systematic review protocol.

BACKGROUND: Symptom burden and adverse treatment effects can negatively impact physical function, health-related outcomes, and quality of life in cancer survivors. Resistive exercise that improves skeletal muscle function can ameliorate these complications, but the central role of the skeletal muscle in mediating improvements in patient-related outcomes has not been explored. This protocol describes the rationale and methods for a systematic review that aims to determine the effects of resistive exercise on the skeletal muscle hypertrophy, muscle performance, and muscle-related biomarkers in cancer survivors. METHODS: A systematic review will be conducted on peer-reviewed randomized controlled trials (RCTs) that employ resistive exercise interventions for cancer survivors. The following electronic databases will be searched: AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus. Studies will be considered for inclusion if they present quantitative data in adult cancer survivors on skeletal muscle characteristics (e.g., muscle mass), muscle performance (e.g., strength), or skeletal muscle-related biomarkers (e.g., myocellular satellite cells). Secondary outcomes will be physical function (e.g., stair climb) and patient-reported outcomes (e.g., fatigue). Data will be reported through a narrative that describes study design, participants, interventions, and outcome characteristics. DISCUSSION: This systematic review will help clarify the influence of resistive exercise on factors relating to the skeletal muscle in adult cancer survivors. Findings may provide insight into optimal exercise selection for evidence-based practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: #277791 [under review].

Reducing Metabolic Dysregulation in Obese Latina and/or Hispanic Breast Cancer Survivors Using Physical Activity (ROSA) Trial: A Study Protocol.

Background: Latina and Hispanic breast cancer survivors (LHBCS) are at increased risk for long-term complications and poorer metabolic health, including metabolic dysregulation (MetD) before and following breast cancer diagnosis. MetD can increase risk of cancer recurrence, death, and comorbid conditions by increasing inflammation and cancer cell proliferation. While exercise improves physical fitness and metabolic outcomes in breast cancer survivors, there is a lack of studies including underrepresented and disadvantaged minority groups such as LHBCS. Methods: Our 12-month randomized (exercise or attention control) controlled trial (the ROSA trial) aims to utilize a progressive combined aerobic and resistance exercise program to improve MetD, insulin resistance, and visceral adiposity among obese LHBCS. We aim to recruit 160 women with Stage I-III breast cancer who are sedentary, centrally obese, and have completed treatment (e.g., surgery, radiation, chemotherapy) prior to enrollment. Participants randomized to the exercise group receive 16-weeks of virtually supervised aerobic and resistance training, followed by 16-weeks of unsupervised home-based aerobic and resistance exercise, and 16-weeks of follow-up. The attention control group receive a 12-month home-based stretching program. Primary and secondary outcomes are measured every 4-weeks during study visits. Discussion: The ROSA trial is the first exercise oncology trial targeting high-risk sedentary, obese LHBCS to improve MetD-related outcomes. Results of this trial will help illuminate how exercise impacts health-related outcomes, survivorship, and recurrence, and inform future exercise oncology guidelines to reduce health disparities among minority cancer survivors.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

Background: Obesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors. Also, it is unclear which exercise prescription would be optimal to maximize the outcomes. Therefore, we designed a randomized controlled trial (Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors [AIM] Trial) to examine the mechanisms by which different modalities of exercise impact chronic inflammation as a biomarker of breast cancer prognosis. Methods: The AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program versus a traditional aerobic and resistance exercise (TARE) program and attention control (AC) on adipose tissue inflammation in breast cancer survivors. 276 patients who are diagnosed with stage 0-III breast cancer, post-treatment, sedentary, and centrally obese are randomized to one of the three groups. The CARE and TARE groups participate in thrice-weekly supervised exercise sessions for 16 weeks. The AC group are offered the CARE program after the intervention period. The primary endpoint is adipose tissue inflammation assessed by core biopsy and blood draw. The secondary and tertiary endpoints are sarcopenic obesity, physical fitness and function, and patient reported outcomes. The exploratory outcomes are long-term breast cancer outcomes. Discussion: This is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Our findings are anticipated to contribute to a better understanding of exercise modalities and mechanisms on adipose tissue inflammation that can potentially improve breast cancer prognosis. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03091842 identifier [NCT#03091842].

Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors.

MOTS-c is a mitochondrial derived peptide with exercise mimetic activity that elicits beneficial effects on metabolism and exercise capacity. Furthermore, MOTS-c effects in humans are affected by race, potentially via ethnic-specific mtDNA variations. Women treated for breast cancer are at an increased risk for cardiovascular disease, diabetes and obesity, due to side effects of cancer-treatments. We conducted a secondary analysis of the effects of a 16-week aerobic and resistance exercise intervention on MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors (BCS). BCS (Stage I-III) were randomized to exercise or standard care. The intervention promoted aerobic and resistance exercise for 16 weeks. MOTS-c was analyzed in fasting plasma using an in-house ELISA. Within and between group differences were assessed by paired t-test and repeated measures ANOVA. Pearson's correlation was computed to assess the association between MOTS-c and metabolic biomarkers at baseline and post-exercise. Twenty-five Hispanic-BCS and 24 non-Hispanic White BCS were included. Hispanic BCS were younger, of greater adiposity, had higher stage cancers, and had worse metabolic profiles at baseline compared to non-Hispanic White BCS (p < 0.001). Post-exercise, MOTS-c levels significantly increased when compared to baseline and the usual care group among non-Hispanic White BCS (p < 0.01) but not among Hispanic breast cancer survivors (p > 0.01). Post-exercise levels of MOTS-c among non-Hispanic White BCS were significantly associated with reductions in fat mass, body weight, HOMA-IR, CRP, and an increase in lean mass (p < 0.01). A 16-week aerobic and resistance intervention increased MOTS-c levels among non-Hispanic White BCS. Trial registration: This trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010. https://clinicaltrials.gov/ct2/show/NCT01140282 .

Aerobic and resistance exercise improve patient-reported sleep quality and is associated with cardiometabolic biomarkers in Hispanic and non-Hispanic breast cancer survivors who are overweight or obese: results from a secondary analysis.

STUDY OBJECTIVES: Poor sleep quality affects nearly one-third of breast cancer survivors and is associated with insulin resistance. The purpose of this secondary analysis was to examine the effects of a 16-week exercise intervention on patient-reported sleep quality among breast cancer survivors and assess whether changes in patient-reported sleep quality were associated with cardiometabolic biomarkers. We explored Hispanic ethnicity as a moderator of the effects of exercise on patient-reported sleep quality. METHODS: Breast cancer survivors who were overweight or obese were randomized to exercise (n = 50) or usual care (n = 50). The 16-week intervention included aerobic and resistance exercise. Patient-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and biomarkers of cardiometabolic health were assessed at baseline and post-intervention. Within- and between-group differences were assessed using general linear models repeated-measures analyses of variance and mixed-model repeated-measure analysis, respectively. Associations between changes in PSQI and cardiometabolic biomarkers were computed using Pearson correlations. Linear mixed-models were used to evaluate effect modification by ethnicity. RESULTS: Participants were 52 ± 10.4 years old, and over half were of Hispanic ethnicity. As compared to usual care, PSQI global scores improved significantly in the exercise group (mean between-group difference -2.2; 95% CI -3.2 to -0.6). Change in PSQI was inversely associated with changes in all cardiometabolic biomarkers (p < 0.01) among the exercise group. Ethnicity was found to moderate the effects of exercise training on global sleep quality (p < 0.001). CONCLUSIONS: An aerobic and resistance exercise intervention effectively improved patient-reported sleep quality in breast cancer survivors. Hispanic ethnicity as a moderator showed greater improvement in patient-reported sleep indicating Hispanic versus non-Hispanic breast cancer survivors may derive larger sleep benefits. CLINICAL TRAIL INFORMATION: NCT01140282.

Aerobic and resistance exercise improves Reynolds risk score in overweight or obese breast cancer survivors.

BACKGROUND: Breast cancer survivors have double the risk of mortality from cardiovascular disease than age-matched women without a cancer history. Reynolds risk score (RRS) is a validated algorithm for the assessment of cardiovascular disease risk. This secondary analysis sought to examine the effects of a 16-week aerobic and resistance exercise intervention on RRS in overweight or obese breast cancer survivors. METHODS AND RESULTS: One hundred overweight or obese (BMI > 25 kg/m2) breast cancer survivors were randomized to exercise or usual care. The exercise group underwent aerobic and resistance exercise sessions for 16 weeks. RRS was calculated using a validated equation. Group differences in mean change for RRS were evaluated using repeated-measures analyses of variance. Post-intervention, RRS was significantly reduced (7.9 ± 0.9% to 1.0 ± 0.5%; p < 0.001) in the exercise group compared to a significant increase (9.0 ± 0.8% to 11.6 ± 1.2%; p = 0.002%) in the usual care group (p < 0.01). RRS was significantly reduced in exercise vs usual care (between group difference, - 10.6; 95% CI, - 16.3 to - 7.4; p < 0.001). CONCLUSION: A 16-week aerobic and resistance exercise intervention is an effective approach to reduce the risk of cardiovascular disease in breast cancer survivors. Exercise during cancer survivorship should be considered to reduce the risk for cardiovascular disease risk in overweight women breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01140282 . Registered 9 June 2010.