Physical Activity Intervention in Patients with Metastatic Breast Cancer During Active Treatment: Quality of Life and Function.

BACKGROUND: In this study, we explore recruitment, retention, and potential quality of life (QoL) and function benefits from a self-directed, home-based walking intervention in women during active treatment for metastatic breast cancer (MBC). METHODS: In this single-arm pilot study, women with stage IV BC wore an activity tracker (FitbitTM) to measure steps per week throughout the intervention study. Participants were asked to walk 150 min per week at a comfortable and safe pace. Patient-reported outcome measures (PRO) were collected at baseline and follow-up. RESULTS: Target recruitment of 60 patients was achieved. In 52 patients who completed all baseline measures, mean age was 55 (SD 11.1), 23% were pre-menopausal, and 19% non-White. Forty patients (77%) were retained at 3 months and 29 (56%) at 6 months. Baseline walking was the strongest predictor of retention at 3 months (P = .02). For 24 patients (46%) with analyzable Fitbit data at 3 months, mean steps/week rose from 19,175 to 31,306. Higher number of steps correlated with larger improvements FACT-G General well-being (FACT-G, rho = 0.55, P = .01), FACT-G Physical well-being (rho = 0.48, P = .03), and PROMIS Mental Health (rho = 0.55, P = .01). CONCLUSION: Recruitment into a walking intervention is feasible (a priory target of N = 60) in women during treatment for MBC, but retention at 3 months follow-up fell short (77% versus a priori 80%), yet there were potential benefits in general and physical well-being and mental health. CLINICALTRIALS.GOV IDENTIFIER: NCT02682836.

Social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in newly diagnosed women with breast cancer.

PURPOSE: Identifying correlates of physical activity and sedentary behaviour allows for the identification of factors that may be targeted in future behaviour change interventions. This study sought to determine the social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in individuals recently diagnosed with breast cancer. METHODS: Data were collected from 1381 participants within 90 days of diagnosis in the Alberta Moving Beyond Breast Cancer (AMBER) Cohort Study. Physical activity and sedentary behaviour were measured with ActiGraph GT3X+® and activPALTM devices, respectively, for seven consecutive days. Correlates were collected via a self-reported questionnaire, medical record extraction, or measured by staff. RESULTS: Multivariable models were fitted for sedentary behaviour, light physical activity, and moderate-to-vigorous physical activity. Greater sedentary behaviour was associated with higher body fat percentage (BF%) (ß=0.044; p<0.001) and being single (ß=0.542; p<0.002). Lower light physical activity was associated with higher BF% (ß=-0.044; p<0.001), higher body mass index (ß=-0.039; p<0.001), greater disease barrier influence (ß=-0.006; p<0.001), a HER2-positive diagnosis (ß=-0.278; p=0.001), and being single (ß=-0.385; p= 0.001). Lower moderate-to-vigorous physical activity was associated with higher BF% (ß =-0.011; p=0.001), greater disease barrier influence (ß=-0.002; p<0.001), and being of Asian (ß=-0.189; p=0.002) or Indian/South American (ß=-0.189; p=0.002) descent. Greater moderate-to-vigorous physical activity was associated with having greater intentions (ß=0.049; p=0.033) and planning (ß=0.026; p=0.015) towards physical activity. CONCLUSION: Tailoring interventions to increase physical activity for individuals recently diagnosed with breast cancer may improve long-term outcomes across the breast cancer continuum.

Multiphasic exercise prehabilitation for patients undergoing surgery for head and neck cancer: a hybrid effectiveness-implementation study protocol.

Head and neck cancer (HNC) treatment often consists of major surgery followed by adjuvant therapy, which can result in treatment-related side effects, decreased physical function, and diminished quality of life. Perioperative nutrition interventions and early mobilization improve recovery after HNC treatment. However, there are few studies on prehabilitation that include exercise within the HNC surgical care pathway. We have designed a multiphasic exercise prehabilitation intervention for HNC patients undergoing surgical resection with free flap reconstruction. We will use a hybrid effectiveness-implementation study design guided by the RE-AIM framework to address the following objectives: (1) to evaluate intervention benefits through physical function and patient-reported outcome assessments; (2) to determine the safety and feasibility of the prehabilitation intervention; (3) to evaluate the implementation of exercise within the HNC surgical care pathway; and (4) to establish a post-operative screening and referral pathway to exercise oncology resources. The results of this study will provide evidence for the benefits and costs of a multiphasic exercise prehabilitation intervention embedded within the HNC surgical care pathway. This paper describes the study protocol design, multiphasic exercise prehabilitation intervention, planned analyses, and dissemination of findings. Trial registration: https://clinicaltrials.gov/NCT04598087.

Baseline fatigue in early breast cancer survivors: understanding its prevalence in community-based exercise.

PURPOSE: Examine baseline fatigue levels in early-breast cancer survivors (EBCS) compared to inactive controls (CON) and identify associated physical and psychosocial factors with fatigue prior to community-based exercise. METHODS: A total of 33 EBCS (53.9 ± 11.4 years) and 21 CON (54.0 ± 8.0 years) were recruited. Participants completed questionnaires for demographics and patient-reported outcome measures pertaining to fatigue, quality of life, mental health, and physical activity, and completed a 6-min walk test, balance assessment, cardiopulmonary exercise test (VO2peak), and muscular strength test. A Mann-Whitney U test compared fatigue between groups and unadjusted univariable linear regressions were used to explore relationships with fatigue. RESULTS: Fatigue in EBCS was not statistically different from CON (EBCS: 16.9 ± 5.75; CON: 14.2 ± 3.4, p = 0.121). Univariable analyses showed lower fatigue in EBCS was associated with better Physical and Mental Health (both R2 = 0.435; p < 0.01), better outcome expectations for exercise (R2 = 0.237; p < 0.01), better self-efficacy (R2 = 0.407; p < 0.01), lower depression (R2 = 0.383; p < 0.001), lower anxiety (R2 = 0.104; p < 0.05), and better balance (R2 = 0.265; p < 0.01). Lower fatigue in the CON group was associated with better sleep quality (R2 = 0.263; p < 0.05) and self-efficacy (R2 = 0.417; p < 0.05). CONCLUSIONS: Mild fatigue was prevalent in EBCS, whereas moderate/severe fatigue was not. This discrepancy should be explored provided the benefits of exercise for fatigue management. Further, fatigue in EBCS was associated with multiple psychosocial and functional outcomes, which emphasized both its multi-factorial nature and uniqueness to the EBCS population. CLINICALTRIALS: gov Number: NCT03760536.

Community-based exercise programs and cancer-related fatigue: a systematic review and meta-analysis.

PURPOSE: To explore the prevalence of cancer-related fatigue (CRF) within community-based exercise programs and to determine the overall impact that participation in community-based exercise programs have on CRF. METHODS: Literature searches were performed in March and updated in April of 2020. Studies that were community-based in adult cancer populations and reported CRF outcomes were included. Mean and standard deviations for CRF from 12 studies were extracted in order to compute a pooled effect size via a random effects model. An overall percentage was computed to discern how many community-based exercise programs reported CRF. RESULTS: Sample sizes varied among studies with most patients being middle-aged with breast cancer in the post-treatment setting. Most programs implemented aerobic + resistance exercise training interventions (~77%). Only ~42% of programs identified in the review reported CRF outcomes. The random effects model produced a pooled effect size of 0.30 (p < 0.001). CONCLUSIONS: Fewer than half of the identified community-based exercise programs reported CRF outcomes (~42%). Of those that did, the random effects model revealed a small yet significant impact on improving CRF after exercise participation, though more research is certainly needed in this area. This review produced promising preliminary evidence for the impact of community-based exercise programs on CRF. As exercise interventions transition to community-based facilities, patients should feel confident that these programs will continue to assist in managing CRF that is commonly experienced across the cancer continuum.

Establishing physical activity in breast cancer: self-report versus activity tracker.

PURPOSE: Establishing accurate estimates of physical activity at baseline is essential for interventions assessing the potential benefits of exercise in adults with cancer. This study compares self-reported physical activity with independent data from activity trackers in women with early breast cancer (BC) recruited into a "walking" intervention during chemotherapy. METHODS: Baseline (pre-intervention) questions inquired about self-reported physical activity-number of walking days/week and minutes/day-in women who were initiating chemotherapy for Stage I-III BC. Activity trackers measured steps per day during the first full week of chemotherapy. Weighted Kappa statistic and Pearson correlation coefficients were used to evaluate agreement and association between self-reported and objectively tracked physical activity levels, respectively. Univariate analyses were conducted to identify variables that may influence congruence between the two measures. RESULTS: In a sample of 161 women, 77% were white, with mean age 56 years. Agreement between self-reported and objectively tracked physical activity was "fair" (kappa coefficient = 0.31), with most patients (59%) over-reporting their physical activity levels. There was weak correlation between the two measures (r = 0.24); however, correlation was strong in participants who were not married (r = 0.53) and/or living alone (r = 0.69). CONCLUSIONS: Objective methods for assessing physical activity (activity trackers, accelerometers) should be used as a complement to self-reported measures to establish credible activity levels for intervention studies seeking to increase physical activity and/or measure the impact of increased physical activity in women with breast cancer.

The Independent Effects of Strength Training in Cancer Survivors: a Systematic Review.

Cancer treatment is associated with adverse changes in strength, body composition, physical function, and quality of life. Exercise training reduces cancer incidence and mortality rates and may offset some of the treatment-related effects. To determine the independent effects of strength training (ST) on the effects of cancer treatment, an initial search was performed in March and then updated in November 2015. Additional articles were identified by scanning references from relevant articles. Studies using traditional ST on strength, body composition, aerobic capacity, functional assessments, and psychosocial parameters were included. Excluded studies had no objective strength measurement or combined ST with additional exercise. Mean and standard deviations from 39 studies across seven cancer types were extracted for main outcomes. ST-induced change scores with 95% confidence intervals were calculated and were evaluated with paired t tests, where appropriate. Twenty to fifty percent improvements in maximal strength were observed, indicating that the ST programs were effective. Physical function was also enhanced (7-38%), although gains were less consistent. Body composition and psychosocial changes were rare, with only a few changes in selected cancer types. As such, ST appears to promote benefits that may be specific to cancer types. Strength was the only consistent outcome that improved in all cancer survivors. However, these gains in strength are still of tremendous importance, given its impact on functionality and quality of life. Several practical considerations for exercise testing, training, and data reporting are presented for consideration to improve the overall depth of the field.

Influence of Lower Extremity Muscle Size and Quality on Stair-Climb Performance in Career Firefighters.

The purpose of this study was to examine the influence of lower extremity muscular size and quality on stair-climb performance (SCP) in career firefighters. Forty-six male career firefighters (age = 37.0 ± 7.2 years; stature = 180.2 ± 6.9 cm; body mass = 108.0 ± 19.8 kg) volunteered for this study. Panoramic ultrasound images of the vastus lateralis and rectus femoris were obtained to determine cross-sectional area (CSA) and echo intensity (EI) of each muscle. The CSA of each muscle was then summed together and normalized to body mass (CSA/BM [QCSA]). Additionally, EI was averaged across both muscles (QEI). Participants then performed a timed and weighted SCP assessment where they ascended and descended 26 stairs 4 times as quickly as possible while wearing a weighted vest (22.73 kg) to simulate the weight of their self-contained breathing apparatus and turnout gear. Bivariate correlations and stepwise regression analyses were used to examine the relationships among variables and the relative contributions of QCSA and QEI to SCP. Partial correlations were used to examine the relationship between QCSA and SCP and QEI and SCP while controlling for age and body mass index (BMI). The results indicated that QCSA and QEI were significantly related to SCP before (r = -0.492, p = 0.001; r = 0.363, p = 0.013, respectively) and after accounting for age and BMI (r = -0.324, p = 0.032; r = 0.413, p = 0.005, respectively). Both QCSA and QEI contributed significantly to the prediction of SCP (r = 0.560, p < 0.001). These findings indicate that lower extremity muscle size and quality are important contributors to critical firefighting tasks, which have been shown to be improved with resistance training.

Understanding the Experiences of Physical Activity, Body Image, and Quality of Life in Young Adult Males Living with and beyond Cancer.

For young adults (YAs), a cancer diagnosis and subsequent treatments may result in physical changes that can negatively impact body image (BI) and health-related quality of life (HRQL). Physical activity (PA) is an evidence-based tool found to impact both BI and HRQL. However, most research has focused on the perspectives of older adults with breast or prostate cancer. No research has explored the experiences of PA, BI, and HRQL in YA males affected by cancer. A qualitative study was designed for YA males diagnosed with cancer between the ages of 20 and 39 years. Eligible participants were recruited through pre-existing exercise oncology studies, support organizations, and social media. Semi-structured interviews were conducted to understand participants' experiences of PA, BI, and HRQL. All interviews were transcribed verbatim and analyzed using interpretive description. The participants were YA males (n = 7) with a mean age of 32.7 ± 4.0 years. Themes included a loss of identity due to cancer, building autonomy and identity using PA, and the "should" behind BI. PA for YA males living with and beyond cancer may support them in rebuilding their identity and BI. The development of exercise oncology resources for YA males may consider addressing BI through education or exercise prescription programs, with the goal of enhancing HRQL.

Effectiveness of a Self-Monitoring App in Supporting Physical Activity Maintenance Among Rural Canadians With Cancer After an Exercise Oncology Program: Cluster Randomized Controlled Trial.

BACKGROUND: Despite the benefits of physical activity (PA) for individuals with cancer, most remain insufficiently active. Exercise oncology interventions can improve PA levels. Individuals struggle to maintain PA levels after interventions because of persistent psychological and environmental PA barriers. Health technology (eHealth) may address some PA barriers and deliver effective, scalable PA interventions in oncology, yet its effectiveness for changing PA levels remains mixed. Using eHealth to support PA maintenance among rural populations with cancer, who may need greater PA support given lower PA levels and worse health outcomes, remains under-studied. OBJECTIVE: This study examined the effectiveness of an app-based self-monitoring intervention in supporting PA maintenance among rural populations with cancer after a supervised web-based exercise oncology program. METHODS: This 2-arm, cluster randomized controlled trial was embedded within the Exercise for Cancer to Enhance Living Well (EXCEL) effectiveness-implementation study. Upon consent, participants were randomized 1:1 by EXCEL class clusters to the intervention (24 weeks of app-based PA self-monitoring) or waitlist control (app access after 24 weeks). Both groups completed a 12-week supervised web-based exercise oncology program followed by a 12-week self-directed PA maintenance period. Baseline demographics, eHealth literacy, and patient-reported outcomes were compared using chi-square and 2-tailed t tests. App use was measured throughout the intervention. The primary outcome-self-reported moderate-to-vigorous PA (MVPA) minutes-and secondary outcomes-objective MVPA minutes and steps and app usability ratings-were collected at baseline, 12 weeks, and 24 weeks. Intervention effects on self-report MVPA maintenance were assessed via linear mixed modeling, with secondary outcomes explored descriptively. RESULTS: Of the 359 eligible EXCEL participants, 205 (57.1%) consented, 199 (55.4%; intervention: 106/199, 53.3%; control: 93/199, 46.7%) started the study, and 183 (51%; intervention: 100/183, 54.6%; control: 83/183, 45.4%) and 141 (39.3%; intervention: 69/141, 48.9%; control: 72/141, 51.1%) completed 12- and 24-week measures, respectively. Mean age was 57.3 (SD 11.5) years. Most participants were female (174/199, 87.4%), White (163/199, 81.9%), and diagnosed with breast cancer (108/199, 54.3%). Median baseline self-report weekly MVPA minutes were 60.0 (IQR 0-180) and 40.0 (IQR 0-135) for the intervention and waitlist control groups, respectively (P=.74). Median app use duration was 10.3 (IQR 1.3-23.9) weeks, with 9.6 (IQR 4.4-17.8) self-monitoring entries/week. Both groups increased their weekly MVPA minutes significantly at 12 weeks (P<.001) and maintained the increases at 24 weeks (P<.001), relative to baseline, with no between-group differences (P=.87). The intervention group had significantly higher step counts for 7 of the 12 weeks during the PA maintenance period (P=.048 to <.001). CONCLUSIONS: The app-based self-monitoring intervention did not improve MVPA maintenance but may have contributed to increased step counts during the PA maintenance period. More work is needed to realize the full potential of eHealth in exercise oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04790578; https://clinicaltrials.gov/study/NCT04790578. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2021.106474.

First-Year Implementation of the EXercise for Cancer to Enhance Living Well (EXCEL) Study: Building Networks to Support Rural and Remote Community Access to Exercise Oncology Resources.

Barriers to exercise-oncology programs remain for those living with and beyond cancer in rural and remote communities, including geographic isolation and access to programs. The EXercise for Cancer to Enhance Living Well (EXCEL) study was designed to support exercise-oncology implementation in rural and remote communities across Canada. The purpose of this analysis was to evaluate the first-year reach, adoption, and implementation of the EXCEL study. Reach outcomes included participant characteristics, study enrolment, and referral type (self vs. healthcare-provider [HCP] referral). Adoption outcomes included the number of clinical contacts, trained qualified exercise professionals (QEPs), and QEPs delivering EXCEL exercise classes. Implementation outcomes included retention, adherence, assessment completion rates, and adverse-event reporting. A total of 290 individuals living with cancer enrolled in EXCEL in year one, with an 81.4% retention to the study intervention. Most participants self-referred to EXCEL (75.8%). EXCEL's HCP network consisted of 163 clinical contacts, and the QEP network included 45 trained QEPs, 22 of whom delivered EXCEL classes. Adherence to the exercise intervention was 78.2%, and only one adverse event (mild) was reported. Fitness assessment and patient-reported outcome completion rates were above 85% pre- and post-intervention. EXCEL has developed HCP and QEP networks supporting exercise referral and online delivery, and the intervention is meeting feasibility markers. These implementation findings will inform the continued gathering of feedback across stakeholders to ensure that best evidence informs best practices.

Tailoring the Evidence for Exercise Oncology within Breast Cancer Care.

Exercise is safe and effective for those living with and beyond breast cancer, with evidence supporting exercise guidelines, and position statements from international organizations. Despite the clearly recognized benefits of exercise for these individuals, many do not participate or maintain recommended exercise levels throughout the breast cancer continuum, highlighting the lack of translation from research into practice. In addition, discerning how exercise can be tailored to address breast cancer-related impairments, so that individuals are able to participate safely and effectively, has also not been studied extensively. Thus, we propose that implementing exercise screening, triage, and referral pathways across the breast cancer continuum may allow for increased accessibility and adoption among those living with and beyond breast cancer. This paper provides an overview of exercise prescription tailoring for common breast cancer and treatment-related impairments, proposes a simplified screening tool for identifying physical activity and movement-related impairments, and considers how best to channel evidence into practice via proposed implementation pathways that may better connect individuals living with and beyond breast cancer with exercise oncology resources through screening, triage, and referral.

Impact of community-based exercise on fatigue in early breast cancer survivors: identifying potential determinants of change.

BACKGROUND: Exercise has been shown to reduce fatigue in early breast cancer survivors (EBCS), though it is unclear if these results translate to community-based exercise settings. Mechanisms that influence changes in fatigue seen after exercise are also poorly understood. This study sought to evaluate the impact of community-based exercise and identify associations of fatigue in EBCS. METHODS: Twenty-nine EBCS and 13 non-cancer controls (CON) enrolled. Pre/post-intervention measurements included measures of fitness/function, balance, and adherence/compliance as well as self-reported measures of fatigue, health-related quality of life (HRQOL), well-being, self-efficacy, and physical activity. Both groups participated in a supervised 16-week aerobic + resistance exercise intervention. A mixed model ANOVA and Cohen's D effect size assessed fatigue changes, and univariable linear regressions identified fatigue associations. RESULTS: Fatigue improved for EBCS (- 2.6, Cohen's D = 0.51) but not CON (0.0, Cohen's D = 0.02); no interaction effect was observed. Post-intervention fatigue in EBCS was associated with better QOL (R2 = 0.387; p < 0.01), depression (R2 = 0.251; p < 0.01), self-efficacy, (R2 = 0.453; p < 0.01), outcome expectations from exercise (R2 = 0.254; p < 0.01), balance (R2 = 0.167; p < 0.05), and the 6-minute walk test (R2 = 0.193; p < 0.05). EBCS improvements in fatigue were associated with improvements in self-reported physical health (R2 = 0.425; p < 0.01), depression (R2 = 0.233; p < 0.01), pain (R2 = 0.157; p < 0.05), outcome expectations from exercise (R2 = 0.420; p < 0.01), and the 6-minute walk test (R2 = 0.172; p < 0.05). Less fatigue in the CON group was shown be associated with better sleep quality (R2 = 0.309; p < 0.05) and pain (R2 = 0.259; p < 0.05). CONCLUSION: Community-based exercise appears beneficial for alleviating fatigue in EBCS. These improvements may be driven by parallel improvements in psychosocial outcomes and objectively measured functional outcomes.

Implementing an exercise oncology model to reach rural and remote individuals living with and beyond cancer: a hybrid effectiveness-implementation protocol for project EXCEL (EXercise for Cancer to Enhance Living Well).

INTRODUCTION: Individuals living with and beyond cancer from rural and remote areas lack accessibility to supportive cancer care resources compared with those in urban areas. Exercise is an evidence-based intervention that is a safe and effective supportive cancer care resource, improving physical fitness and function, well-being and quality of life. Thus, it is imperative that exercise oncology programs are accessible for all individuals living with cancer, regardless of geographical location. To improve accessibility to exercise oncology programs, we have designed the EXercise for Cancer to Enhance Living Well (EXCEL) study. METHODS AND ANALYSIS: EXCEL is a hybrid effectiveness-implementation study. Exercise-based oncology knowledge from clinical exercise physiologists supports healthcare professionals and community-based qualified exercise professionals, facilitating exercise oncology education, referrals and programming. Recruitment began in September 2020 and will continue for 5 years with the goal to enroll ~1500 individuals from rural and remote areas. All tumour groups are eligible, and participants must be 18 years or older. Participants take part in a 12-week multimodal progressive exercise intervention currently being delivered online. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework is used to determine the impact of EXCEL at participant and institutional levels. Physical activity, functional fitness and patient-reported outcomes are assessed at baseline and 12-week time points of the EXCEL exercise intervention. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of Alberta. Our team will disseminate EXCEL information through quarterly newsletters to stakeholders, including participants, qualified exercise professionals, healthcare professionals and community networks. Ongoing outreach includes community presentations (eg, support groups, fitness companies) that provide study updates and exercise resources. Our team will publish manuscripts and present at conferences on EXCEL's ongoing implementation efforts across the 5-year study. TRIAL REGISTRATION NUMBER: NCT04478851.

Impact of community-based exercise program participation on aerobic capacity in women with and without breast cancer.

BACKGROUND: Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM: To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS: A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS: The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION: Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Exercise training partially rescues impaired mucosal associated invariant t-cell mobilization in breast cancer survivors compared to healthy older women.

Exercise may attenuate immunosenescence with aging that appears to be accelerated following breast cancer treatment, although limited data on specific cell types exists and acute and chronic exercise have been investigated independently in older adults. PURPOSE: To determine the mucosal associated invariant T (MAIT) cell response to acute exercise before (PRE) and after (POST) 16 weeks of exercise training in breast cancer survivors (BCS) and healthy older women (CON). METHODS: Age-matched BCS and CON performed 45 min of intermittent cycling at 60% peak power output wattage. Blood samples were obtained at rest, immediately (0 h) and 1 h after exercise to determine MAIT cell counts, frequency, and intracellular cytokine expression. RESULTS: At PRE, MAIT cell counts were greater in CON (137%) than BCS at 0 h (46%, p < 0.001), with increased MAIT cell frequency in CON but not BCS. TNFα+ and IFNγ+ MAIT cell counts increased at 0 h by ~120% in CON (p < 0.001), while BCS counts and frequencies were unchanged. Similar deficits were observed in CD3+ and CD3+ CD8+ cells. At POST, exercise-induced mobilization and egress of MAIT cell counts and frequency showed trends towards improvement in BCS that approached levels in CON. Independent of group, TNFα frequency trended to improve (p = 0.053). CONCLUSIONS: MAIT mobilization in older BCS following acute exercise was attenuated; however, exercise training may partially rescue these initial deficits, including greater sensitivity to mitogenic stimulation. Using acute exercise before and after interventions provides a unique approach to identify age- and cancer-related immuno-dysfunction that is less apparent at rest.

Exercise-induced modulation of monocytes in breast cancer survivors.

BACKGROUND: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. OBJECTIVES: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. METHODS: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. RESULTS: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß+CD14+CD16+ MFI (-11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (-63, p=0.002) and CD14+CD16+ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. CONCLUSIONS: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors.

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03760536.

Cardiovascular Consequences of Skeletal Muscle Impairments in Breast Cancer.

Breast cancer survivors suffer from disproportionate cardiovascular disease risk compared to age-matched controls. Beyond direct cardiotoxic effects due to treatments such as chemotherapy and radiation, breast-cancer-related reductions in skeletal muscle mass, quality and oxidative capacity may further contribute to cardiovascular disease risk in this population by limiting the ability to engage in aerobic exercise-a known promoter of cardiovascular health. Indeed, 20%-30% decreases in peak oxygen consumption are commonly observed in breast cancer survivors, which are indicative of exercise intolerance. Thus, breast-cancer-related skeletal muscle damage may reduce exercise-based opportunities for cardiovascular disease risk reduction. Resistance training is a potential strategy to improve skeletal muscle health in this population, which in turn may enhance the capacity to engage in aerobic exercise and reduce cardiovascular disease risk.

Two weeks of lower body resistance training enhances cycling tolerability to improve precision of maximal cardiopulmonary exercise testing in sedentary middle-aged females.

It is not uncommon for sedentary individuals to cite leg fatigue as the primary factor for test termination during a cardiopulmonary exercise test (CPET) on a cycle ergometer. The purpose of this study was to examine the effect of 2 weeks of lower body resistance training (RT) on cardiopulmonary capacity in sedentary middle-aged females. Additionally, the impact of RT on muscle strength was evaluated. Following familiarization, 28 women (18 exercise group, 10 control group) completed a maximal CPET on a cycle ergometer to determine peak oxygen uptake and leg extensor strength assessed using isokinetic dynamometry. Participants in the exercise group performed 2 weeks (6 sessions) of lower body RT, which comprised leg press, leg curl, and leg extension exercises. A 2-way repeated-measures ANOVA was used to evaluate the difference in changes of peak oxygen uptake and peak torque (PT). Peak oxygen uptake significantly improved from 22.2 ± 4.5 mL·kg-1·min-1 to 24.3 ± 4.4 mL·kg-1·min-1 (10.8%, p < 0.05) as well as PT from 83.1 ± 25.4 Nm to 89.0 ± 29.7 Nm (6.1%, p < 0.05) in the exercise group with no change in the control group. These findings provide initial evidence that 2 weeks of lower body RT prior to a CPET may be a helpful preconditioning strategy to achieve a more accurate peak oxygen uptake during testing, enhancing tolerability to a CPET by improving lower body strength.