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Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.

ABSTRACT: Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The CON group was offered the HIIT intervention after 8 weeks. MMP-1, -2 -7, -9, tissue inhibitor of MMP (TIMP) -1, and-2 were measured at baseline and post-intervention. Repeated measures ANCOVA and paired t-test were performed to assess changes in MMP and TIMP. Post-intervention, no significant between-group differences were observed for MMP and TIMP. However, within-group decrease in MMP-9 was observed in the HIIT group [104.3(51.9) to 65.2(69.1); P?=?0.01]. MMP-9 in the CON group was not significantly changed [115.5(47.2) to 90.4(67.9);]. MMP-2 significantly increased in both the HIIT group [76.6(11.2) to 83.2(13.1); P?=?0.007) and the CON group [69.0(8.9) to 77.6(11.1) P?=?0.003). It is unclear whether an 8-week HIIT intervention influences MMP-9 in breast cancer patients undergoing anthracycline chemotherapy. Additional investigations are required to understand the exercise-induced changes in MMP-2 and -9 in women undergoing anthracycline chemotherapy.

SUBMITTER: Lee K

PROVIDER: S-EPMC7125197 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.

Lee Kyuwan K Kang Irene I Mack Wendy J WJ Mortimer Joanne J Sattler Fred F Salem George G Dieli-Conwright Christina M CM

Scientific reports 20200403 1

Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The C ...[more]

PMID: 32246106

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Project description:BACKGROUND:Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. METHODS:Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO2max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). RESULTS:Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO2max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group (p = 0.94) while there was a significant decrease in VO2max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks (p = 0.001). CONCLUSIONS:HIIT is a feasible exercise intervention to maintain VO2max in breast cancer patients receiving anthracycline-based chemotherapy. TRIAL REGISTRATION:The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).

Project description:INTRODUCTION:Cardiovascular disease (CVD) mortality is higher among breast cancer survivors (BCS) who receive chemotherapy compared with those not receiving chemotherapy. Anthracycline chemotherapy is of particular concern due to anthracycline-related impairment of vascular endothelial cells and dysregulation of the extracellular matrix. One strategy proven to offset these impairments is a form of exercise known as high-intensity interval training (HIIT). HIIT improves endothelial function in non-cancer populations by decreasing oxidative stress, the main contributor to anthracycline-induced vascular dysfunction. The purpose of this pilot study is to assess the feasibility of an 8-week HIIT, as well as the HIIT effects on endothelial function and extracellular matrix remodelling, in BCS undergoing anthracycline chemotherapy. METHODS AND ANALYSIS:Thirty BCS are randomised to either HIIT, an 8-week HIIT intervention occurring three times per week (seven alternating bouts of 90% of peak power output followed by 10% peak power output), or delayed group (DEL). Feasibility of HIIT is assessed by (1) the percentage of completed exercise sessions and (2) the number of minutes of exercise completed over the course of the study. Vascular function is assessed using brachial artery flow-mediated dilation and carotid intima media thickness. Extracellular matrix remodelling is assessed by the level of matrix metalloproteinases in the plasma. A repeated-measures analysis of covariance model will be performed with group (HIIT and DEL group) and time (pre/post assessment) as independent factors. We hypothesise that HIIT will be feasible in BCS undergoing anthracycline chemotherapy, and that HIIT will improve endothelial function and extracellular matrix remodelling, compared with the DEL group. Success of this study will provide evidence of feasibility and efficacy to support a larger definitive trial which will impact cancer survivorship by decreasing anthracycline-induced vascular dysfunction, thereby benefiting cardiovascular markers that are related to CVD risk. ETHICS AND DISSEMINATION:This trial was approved by the University of Southern California Institutional Review Board (HS-15-00227). TRIAL REGISTRATION NUMBER:NCT02454777; Pre-results.

Project description:BackgroundMore than 75% of patients with breast cancer treated with chemotherapy experience cognitive impairments (eg, memory and attention problems), commonly known as chemo-brain. Exercise, especially aerobic high-intensity interval training (HIIT), is associated with better cognitive function in healthy populations. However, clinical trials testing the impact of exercise interventions on chemotherapy-induced cognitive decline in patients with cancer are lacking, and the mechanisms through which exercise could improve cognitive function are unclear.ObjectiveThe objective of the Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy trial is to examine the effects of HIIT on cognitive function in patients with breast cancer undergoing chemotherapy.MethodsThis 2-arm, single-center, pilot randomized controlled trial will randomize 50 patients with breast cancer undergoing chemotherapy to HIIT or attention control. The HIIT group will perform a supervised 16-week, thrice-weekly intervention, with each session including a 5-minute warm-up at 10% maximal power output (POmax), 10 sets of alternating 1-minute high-intensity (90% POmax) and 1-minute recovery (10% POmax) intervals, and a 5-minute cooldown (10% POmax). The attention control group will receive a stretching program with no exercise components and be asked to maintain their exercise levels for 16 weeks. The primary outcomes of the study are executive function and memory measured using the National Institutes of Health toolbox and resting-state connectivity and diffusion tensor imaging microstructure evaluated using magnetic resonance imaging. The secondary and tertiary outcomes include cardiorespiratory fitness, body composition, physical fitness, and psychosocial health. The study has been approved by the institutional review board of the Dana-Farber Cancer Institute (20-222).ResultsThe trial was funded in January 2019, with recruitment started in June 2021. As of May 2022, a total of 4 patients have consented and been randomized (n=2, 50% to exercise; n=1, 25% to control; and n=1, 25% nonrandomized). Trial completion is expected in January 2024.ConclusionsThis first-of-its-kind study incorporates a novel exercise intervention (ie, HIIT) and comprehensive cognitive measures. If positive, our findings will establish the pilot efficacy of HIIT on chemotherapy-induced cognitive function in patients with breast cancer, providing the foundation for future larger phase-II and phase-III trials to confirm the findings and potentially establish HIIT as a standard of care for women undergoing chemotherapy for breast cancer.Trial registrationClinicalTrials.gov NCT04724499; https://clinicaltrials.gov/ct2/show/NCT04724499.International registered report identifier (irrid)DERR1-10.2196/39740.

Project description:BackgroundUp to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients' self-perceived cognitive functioning and common cancer related side-effects, will be explored.MethodsA single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients' first-line chemotherapy treatment typically lasting 12-18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients' change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance).DiscussionThis study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients.Trial registrationDRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390 , Registered on 17 January 2018.

Dataset Information

Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.

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Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.

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