Exercise and health-related fitness predictors of chemotherapy completion in breast cancer patients: pooled analysis of two multicenter trials.

PURPOSE: Achieving a higher chemotherapy completion rate is associated with better outcomes in breast cancer patients. We examined the role of exercise and health-related fitness variables in predicting chemotherapy completion in early stage breast cancer patients. METHODS: We pooled data from two large, multicenter, exercise trials that obtained baseline (pre-chemotherapy) measures of exercise and health-related fitness in 543 breast cancer patients initiating adjuvant chemotherapy. Assessments included body composition, cardiovascular fitness, muscular strength, patient-reported physical functioning, and self-reported exercise behavior. Chemotherapy completion was assessed as the average relative dose intensity (RDI) for the originally planned regimen. We used logistic regression analyses with a two-sided p value of < 0.05 to estimate the associations between the predictors and an RDI of ≥ 85%. RESULTS: Overall, 432 of 543 (79.6%) breast cancer patients received an RDI of ≥ 85%. In logistic regression analyses adjusted for significant covariates, patients in the highest 20% vs. lowest 80% of absolute VO2peak were significantly more likely to complete ≥ 85% RDI (89.0% vs. 77.2%; ORadj 2.06, 95% CI 1.07-3.96, p = 0.031). Moreover, patients in the highest 80% vs. lowest 20% of absolute chest strength were significantly more likely to complete ≥ 85% RDI (81.5% vs. 71.4%; ORadj 1.80, 95% CI 1.09-2.98, p = 0.021). CONCLUSIONS: In these exploratory analyses, higher baseline (pre-chemotherapy) cardiovascular fitness and muscular strength were associated with higher rates of chemotherapy completion in early stage breast cancer patients. Aerobic and/or strength training interventions that increase cardiovascular fitness and muscular strength prior to chemotherapy for breast cancer may improve treatment tolerability and outcomes. CLINICAL TRIAL REGISTRATION: START: NCT00115713, June 24, 2005; CARE: NCT00249015, November 7, 2005 ( http://clinicaltrials.gov ).

Effects of exercise dose and type during breast cancer chemotherapy on longer-term patient-reported outcomes and health-related fitness: A randomized controlled trial.

The Combined Aerobic and Resistance Exercise (CARE) Trial compared different types and doses of exercise performed during breast cancer chemotherapy. Here, we report the longer-term follow-up of patient-reported outcomes, health-related fitness and exercise behavior at 6, 12 and 24 months postintervention. A multicenter trial in Canada randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101) or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104) performed for the duration of chemotherapy (median of 17 weeks). Primary outcomes were patient-reported outcomes including quality of life, cancer-related symptoms and psychosocial outcomes. Secondary outcomes were objective health-related fitness (assessed at 12 months only) and self-reported exercise behavior. A total of 269 (89.4%) participants completed patient-reported outcomes at all three follow-up time points and 263 (87.4%) completed the health-related fitness assessment at 12-month follow-up. COMB was significantly superior to (i) STAN for sleep quality at 6-month follow-up (p = 0.027); (ii) HIGH for upper body muscular endurance at 12-month follow-up (p = 0.020); and (iii) HIGH for meeting the resistance exercise guideline at 6-month follow-up (p = 0.006). Moreover, self-reported meeting of the combined exercise guideline during follow-up was significantly associated with better patient-reported outcomes and health-related fitness. Performing combined exercise during and after breast cancer chemotherapy may result in better longer-term patient-reported outcomes and health-related fitness compared to performing aerobic exercise alone.

Exercise training affects hemodynamics not cardiac function during anthracycline-based chemotherapy.

INTRODUCTION: Preclinical data demonstrate the potential for exercise training to protect against anthracycline-related cardiotoxicity, but this remains to be shown in humans. PURPOSE: To assess whether exercise training during anthracycline-based chemotherapy for treatment of breast cancer affects resting cardiac function and hemodynamics. METHODS: In this prospective, non-randomized controlled study, 26 women who participated in aerobic and resistance training 3×/wk during chemotherapy were compared to 11 women receiving usual care. Two-dimensional echocardiography was performed before and 7-14 days after completion of anthracycline-based chemotherapy. Pre- and post-anthracycline cardiac function and hemodynamic variables were compared within each group with paired t-tests; the change was compared between groups using ANCOVA with adjustment for baseline values. RESULTS: Left ventricular longitudinal strain, volumes, ejection fraction, E/A ratio, and mass did not change in either group. Hemoglobin, hematocrit, and mean arterial pressure decreased significantly from baseline in both groups (all p < 0.05) with no differences between groups. Cardiac output increased in the usual care group only (+ 0.27 ± 0.24 L/min/m2, p < 0.01), which differed significantly from the exercise group (p = 0.03). Systemic vascular resistance (SVR) decreased in both groups (usual care: - 444, p < 0.01; exercise: - 265, dynes/s/cm5, p = 0.01). However, the reduction in SVR was significantly attenuated in the exercise group (p = 0.03) perhaps due to a compensatory decrease in estimated vessel lumen radius. CONCLUSION: Exercise training during anthracycline chemotherapy treatment had no effect on resting cardiac function but appeared to modify hemodynamic responses. Specifically, exercise training attenuated the drop in SVR in response to chemotherapy-related reductions in hematocrit potentially by increasing vessel lumen radius.

Peripheral chemoresponsiveness during exercise in male athletes with exercise-induced arterial hypoxaemia.

NEW FINDINGS: What is the central question of this study? Do highly trained male endurance athletes who develop exercise-induced arterial hypoxaemia (EIAH) demonstrate reduced peripheral chemoresponsiveness during exercise? What is the main finding and its importance? Those with the lowest arterial saturation during exercise have a smaller ventilatory response to hypercapnia during exercise. There was no significant relationship between the hyperoxic ventilatory response and EIAH. The findings suggest that peripheral chemoresponsiveness to hypercapnia during exercise could play a role in the development of EIAH. The findings improve our understanding of the mechanisms that contribute to EIAH. ABSTRACT: Exercise-induced arterial hypoxaemia (EIAH) is characterized by a decrease in arterial oxygen tension and/or saturation during whole-body exercise, which may in part result from inadequate alveolar ventilation. However, the role of peripheral chemoresponsiveness in the development of EIAH is not well established. We hypothesized that those with the most severe EIAH would have an attenuated ventilatory response to hyperoxia and hypercapnia during exercise. To evaluate this, on separate days, we measured ventilatory sensitivity to hyperoxia and separately hypercapnia at rest and during three different exercise intensities (25, 50% of V̇O2max and ventilatory threshold (∼67% of V̇O2max )) in 12 males cyclists ( V̇O2max  = 66.6 ± 4.7 ml kg-1  min-1 ). Subjects were divided into two groups based on their end-exercise arterial oxygen saturation (ear oximetry, SpO2 ): a normal oxyhaemoglobin saturation group (NOS, SpO2  = 93.4 ± 0.4%, n = 5) and a low oxyhaemoglobin saturation group (LOS, SpO2  = 89.9 ± 0.9%, n = 7). There was no difference in V̇O2max (66.4 ± 2.9 vs. 66.8 ± 6.0 ml kg-1  min-1 , respectively, P = 0.9), peak ventilation during maximal exercise (182 ± 15 vs. 197 ± 32 l min-1 , respectively, P = 0.36) or ventilatory response to hyperoxia (P = 0.98) at any exercise intensity between NOS and LOS groups. However, those in the LOS group had a significantly lower ventilatory response to hypercapnia (P = 0.004, (η2  = 0.18). There was also a significant relationship between the mean hypercapnic response and end-exercise SpO2 (r = 0.75, P = 0.009) but not between the mean hyperoxic response and end-exercise SpO2 (r = 0.21, P = 0.51). A blunted hypercapnic ventilatory response may contribute to EIAH in highly trained men due to a failure to increase ventilation sufficiently to offset exercise-induced gas exchange impairments.

Impact of Exercise on Chemotherapy Tolerance and Survival in Early-Stage Breast Cancer: A Nonrandomized Controlled Trial.

BACKGROUND: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. PATIENTS AND METHODS: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. RESULTS: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54-1.11) or delay (RR, 1.05; 95% CI, 0.62-1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54-84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). CONCLUSIONS: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.

Patterns and predictors of exercise behavior during 24 months of follow-up after a supervised exercise program during breast cancer chemotherapy.

BACKGROUND: Understanding the longer-term exercise behavior of patients with breast cancer after chemotherapy is important to promote sustained exercise. The purpose of the current study was to report the longer-term patterns and predictors of exercise behavior in patients with breast cancer who exercised during chemotherapy. METHODS: In the Combined Aerobic and Resistance Exercise (CARE) Trial, 301 patients with breast cancer were randomized to three different exercise prescriptions during chemotherapy. Exercise behaviors after chemotherapy were self-reported at 6-, 12-, and 24-month follow-up. Exercise patterns were identified by categorizing patients according to which exercise guideline they were meeting (neither, aerobic only, resistance only, or combined) at each of the three follow-up timepoints (64 possible patterns). Predictors of longer-term exercise behavior included physical fitness, patient-reported outcomes, and motivational variables from the theory of planned behavior assessed at postintervention (postchemotherapy). Univariate and multivariate stepwise multinomial logistic regression and linear regression were used for statistical analyses. RESULTS: A total of 264 (88%) participants completed all three follow-up exercise behavior assessments and exhibited 50 different exercise patterns. Postintervention aerobic fitness was the most consistent predictor of longer-term exercise behavior at all three timepoints. For example, higher aerobic fitness (per 1 ml/kg/min) predicted better adherence to the "aerobic only" (OR = 1.09; p = 0.005) and "combined" (OR = 1.12; p < 0.001) guidelines compared to "neither" guideline at 6-month follow-up. Additionally, higher postintervention muscular strength (per 1 kg) was associated with better adherence to the "resistance only" (OR = 1.07; p = 0.025) and "combined" (OR = 1.08; p < 0.001) guidelines compared to "neither" guideline at 24-month follow-up. Finally, lower perceived difficulty (per 1 scale point) was associated with better adherence to the "combined" (OR = 0.62; p = 0.010) and "aerobic only" (OR = 0.58; p = 0.002) guideline compared to the "neither" guideline at the 24-month follow-up. CONCLUSIONS: Our study is the first to show that the longer-term exercise patterns of patients with breast cancer who exercised during chemotherapy are diverse and predicted by physical fitness and motivational variables after chemotherapy. Our novel implications are that improving physical fitness during chemotherapy and applying motivational counseling after chemotherapy may improve longer-term exercise behavior in patients with breast cancer. TRIAL REGISTRATION: (NCT00249015).

A Longitudinal Study of the Association of Clinical Indices of Cardiovascular Autonomic Function with Breast Cancer Treatment and Exercise Training.

BACKGROUND: Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left-sided radiation for breast cancer are associated with negative autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy. SUBJECTS, MATERIALS, AND METHODS: Seventy-three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HRrest) and blood pressure were measured weekly during chemotherapy. HRrest, exercise heart rate recovery (HRrecovery), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment. RESULTS: During chemotherapy, HRrest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%-51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left-sided radiation individually predicted impairments of HRrest and HRrecovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice-weekly exercise attendance predicted improvement. By 10 weeks after treatment, HRrest and blood pressure were not different from prechemotherapy. CONCLUSION: In this study, chemotherapy resulted in increased HRrest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left-sided radiation were associated with HRrest elevations and impairments of HRrecovery, but exercise training at least twice a week appeared to mitigate these changes. IMPLICATIONS FOR PRACTICE: This study characterized changes in clinically accessible measures with well-established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy-related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60-minute sessions of moderate-intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists.

Effectiveness of Oncologist-Referred Exercise and Healthy Eating Programming as a Part of Supportive Adjuvant Care for Early Breast Cancer.

BACKGROUND: Randomized trials have established efficacy of supervised exercise training during chemotherapy for breast cancer for numerous health outcomes. The purpose of this study was to assess reach, effectiveness, maintenance, and implementation of an evidence-based exercise and healthy eating program offered within an adjuvant care setting. SUBJECTS, MATERIALS, AND METHODS: Women receiving adjuvant chemotherapy for breast cancer were given a prescription by their oncologist to participate in the Nutrition and Exercise during Adjuvant Treatment (NExT) program. The NExT program consisted of supervised, moderate-intensity, aerobic and resistance exercise three times a week during adjuvant therapy, followed by a step-down in supervised sessions per week for 20 additional weeks, plus one group-based healthy eating session. Usual moderate-to-vigorous physical activity (MVPA) and health-related quality of life (HRQoL) were assessed by questionnaire at baseline, program completion, and one year later, along with measures of satisfaction and safety. RESULTS: Program reach encompassed referral of 53% of eligible patients, 78% uptake (n = 73 enrolled), and 78% retention for the 45.0 ± 8.3-week program. During the program, MVPA increased (116 ± 14 to 154 ± 14 minutes per week, p = .014) and HRQoL did not change. One year later, MVPA (171 ± 24 minutes per week, p = .014) and HRQoL (44 ± 1 to 49 ± 1, p < .001) were significantly higher than baseline. Exercise adherence was 60% ± 26% to three sessions per week during treatment. No major adverse events occurred and injury prevalence did not change relative to baseline. Participants were highly satisfied. CONCLUSION: This oncologist-referred exercise and healthy eating supportive-care program for breast cancer patients receiving chemotherapy was safe, successful in reaching oncologists and patients, and effective for improving MVPA and maintaining HRQoL. IMPLICATIONS FOR PRACTICE: Despite evidence that exercise is both safe and efficacious at improving physical fitness, quality of life, and treatment side effects for individuals with cancer, lifestyle programming is not offered as standard of cancer care. This study describes an oncologist-referred, evidence-based exercise and healthy eating program offered in collaboration with a university as supportive care to women with breast cancer receiving chemotherapy. The program was well received by oncologists and patients, safe, and relatively inexpensive to operate. Importantly, there was a significant positive impact on physical activity levels and health-related quality of life lasting for 2 years after initiation of therapy.

Predictors of attendance to an oncologist-referred exercise program for women with breast cancer.

PURPOSE: While exercise is associated with numerous benefits in women with breast cancer, adherence to exercise training concurrent to cancer treatment is challenging. We aimed to identify predictors of attendance to an oncologist-referred exercise program offered during and after adjuvant breast cancer treatment. METHODS: Women with early-stage breast cancer receiving chemotherapy (n = 68) enrolled in the Nutrition and Exercise During Adjuvant Treatment (NExT) study. Supervised aerobic and resistance exercise was prescribed three times per week during treatment, then one to two times per week for 20 additional weeks. Predictors of attendance were identified using multivariate linear regression for three phases of the intervention, including during (1) adjuvant chemotherapy, (2) radiation, and (3) 20-weeks post-treatment. RESULTS: Higher baseline quality of life (QoL) predicted higher attendance during chemotherapy (ß = 0.51%, 95 CI: 0.09, 0.93) and radiation (ß = 0.85%, 95 CI: 0.28, 1.41), and higher QoL, measured at the end of treatment, predicted higher attendance post-treatment (ß = 0.81%, 95 CI: 0.34, 1.28). Being employed pre-treatment (ß = 34.08%, 95 CI: 5.71, 62.45) and a personal annual income > $80,000 (ß = 32.70%, 95 CI: 0.85, 64.55) predicted higher attendance during radiation. Being divorced, separated or widowed (ß = - 34.62%, 95 CI: - 56.33, - 12.90), or single (ß = - 25.38%, 95 CI: - 40.64, - 10.13), relative to being married/common-law, and undergoing a second surgery (ß = - 21.37%, 95 CI: - 33.10, - 9.65) predicted lower attendance post-treatment. CONCLUSIONS: Demographic variables, QoL, and receipt of a second surgery significantly predicted attendance throughout the NExT supervised exercise program. These results may help identify individuals with exercise adherence challenges and improve the design of future interventions, including optimizing the timing of program delivery.

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans.

NEW FINDINGS: What is the central question of this study? This study is the first to measure objectively both inspiratory and expiratory muscle fatigue after inspiratory resistive loading to determine whether the expiratory muscles are activated to the point of fatigue when specifically loading the inspiratory muscles. What is the main finding and its importance? The absence of abdominal muscle fatigue suggests that future studies attempting to understand the neural and circulatory consequences of diaphragm fatigue can use inspiratory resistive loading without considering the confounding effects of abdominal muscle fatigue. Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel coactivation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are likewise coactivated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths min-1 , 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw ) and transdiaphragmatic twitch pressure (Pdi,tw ) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in Pga,tw or Pdi,tw . Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. The Pdi,tw was significantly lower than baseline (34.3 ± 9.6 cmH2 O) at 3 (23.2 ± 5.7 cmH2 O, P < 0.001), 15 (24.2 ± 5.1 cmH2 O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH2 O, P < 0.001). The Pga,tw was not significantly different from baseline (37.6 ± 17.1 cmH2 O) at 3 (36.5 ± 14.6 cmH2 O), 15 (33.7 ± 12.4 cmH2 O) and 30 min post-IRL (32.9 ± 11.3 cmH2 O). Inspiratory resistive loading elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.

Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial.

The purpose of this study was to conduct an exploratory analysis of the START examining the effects of resistance exercise training (RET) and aerobic exercise training (AET) on sarcopenia, dynapenia, and associated quality of life (QoL) changes in breast cancer (BC) patients receiving adjuvant chemotherapy. Participants were randomized to usual care (UC) (n = 70), AET (n = 64), or RET (n = 66) for the duration of chemotherapy. Measures of sarcopenia [skeletal muscle index (SMI)] and dynapenia [upper extremity (UE) and lower extremity (LE) muscle dysfunction (MD)] were normalized relative to age-/sex-based clinical cut-points. QoL was assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scales. At baseline, 25.5 % of BC patients were sarcopenic and 54.5 % were dynapenic with both conditions associated with poorer QoL. ANCOVAs showed significant differences favoring RET over UC for SMI (0.32 kg/m(2); p = 0.017), UE-MD (0.12 kg/kg; p < 0.001), and LE-MD (0.27 kg/kg; p < 0.001). Chi-square analyses revealed significant effects of RET, compared to UC/AET combined, on reversing sarcopenia (p = 0.039) and dynapenia (p = 0.019). The reversal of sarcopenia was associated with clinically relevant improvements in the FACT-An (11.7 points [95 % confidence interval (CI) -4.2 to 27.6]), the Trial Outcome Index-Anemia (10.0 points [95 % CI -4.0 to 24.1]), and fatigue (5.3 points [95 % CI -1.5 to 12.1]). Early-stage BC patients initiating adjuvant chemotherapy have higher than expected rates of sarcopenia and dynapenia which are associated with poorer QoL. RET during adjuvant chemotherapy resulted in the reversal of both sarcopenia and dynapenia; however, only the reversal of sarcopenia was associated with clinically meaningful improvements in QoL.

Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial.

BACKGROUND: Exercise is beneficial for breast cancer patients during chemotherapy, but their motivation to perform different types and doses of exercise is unknown. PURPOSE: The purpose of this study was to examine the anticipated and experienced motivation of breast cancer patients before and after three different exercise programs during chemotherapy. METHODS: Breast cancer patients initiating chemotherapy (N = 301) were randomized to a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a combined dose of 50-60 min of aerobic and resistance exercise. Patient preference and motivational outcomes from the theory of planned behavior (i.e., perceived benefit, enjoyment, support, difficulty, and motivation) were assessed before and after the interventions. RESULTS: At pre-randomization, breast cancer patients were significantly (p < 0.001) more likely to prefer the combined program (80.1 %); however, after the interventions there was a significant (p < 0.001) increase in the number of patients preferring the high volume program and having no preference. At pre-randomization, breast cancer patients anticipated more favorable motivational outcomes for the combined program and less favorable motivational outcomes for the high volume program (all p < 0.001). After the interventions, the motivational outcomes experienced exceeded the anticipated motivational outcomes significantly more in the high volume group than the standard or combined groups. CONCLUSIONS: Anticipated motivational outcomes for different types and doses of exercise during chemotherapy varied considerably at pre-randomization, but the motivational outcomes experienced after the three interventions were similar. Clinicians can recommend any of the three exercise interventions to breast cancer patients knowing that positive motivational outcomes will result. Clinicaltrials.gov identifier: NCT00249015 .

Interval versus continuous aerobic exercise training in breast cancer survivors--a pilot RCT.

BACKGROUND: Exercise therapy is being explored in a variety of cancer populations to counteract treatment-related deconditioning. Higher intensity interval protocols are being prescribed to improve physical function and attenuate surrogates of comorbidity in non-cancer populations. The purpose of this study is to explore the safety of higher intensity exercise stimuli on cardiorespiratory fitness (VO2peak) in breast cancer survivors. METHODS: Postmenopausal breast cancer survivors were randomized into three groups: supervised aerobic interval training (AIT), supervised continuous moderate exercise training (CMT), and an unsupervised control group (CON). For 6 weeks, AIT exercised between 70 and 100% VO2peak, while CMT exercised between 60 and 70% VO2peak. Both groups followed a matched-work design. RESULTS: Thirty-three participants completed the study (age, 57.2 (9) years; weight, 67.6 (12) kg) with no adverse advents. Between-group baseline values were non-significant. VO2peak at baseline (25.3 (5.4) mL·kg(-1)·min(-1)) was below population norms. Compared to CON, cardiorespiratory fitness improved in AIT and CMT by 12% (P < 0.001) with no significant difference between exercise groups. AIT had a greater influence on lower extremity strength (P = 0.026) and body weight (P = 0.031). CONCLUSION: This pilot study provides evidence that similar to CMT, AIT can safely increase VO2peak in a small group of breast cancer survivors. Further exploration of the benefits of implementing higher intensity training protocols is warranted.

Effects of exercise dose and type on sleep quality in breast cancer patients receiving chemotherapy: a multicenter randomized trial.

To examine the effects of different doses and types of exercise on sleep quality in breast cancer patients receiving chemotherapy. A multicenter trial in Canada randomized 301 breast cancer patients between 2008 and 2011 to thrice weekly, supervised exercise during chemotherapy consisting of either a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101), or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104). The secondary sleep outcomes in the trial were assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline, twice during chemotherapy, and postchemotherapy. We analyzed the global PSQI and the component scores. Repeated measures analyses of variance indicated that the HIGH group was statistically superior to the STAN group for global sleep quality (mean group difference = -0.90; 95 % CI -0.05 to -1.76; p = 0.039) as well as subjective sleep quality (p = 0.028) and sleep latency (p = 0.049). The COMB group was borderline statistically superior to the STAN group for global sleep quality (mean group difference = -0.76; 95 % CI +0.11 to -1.62; p = 0.085) as well as sleep duration (p = 0.051); and statistically superior for sleep efficiency (p = 0.040), and percentage of poor sleepers (p = 0.045). Compared to a standard volume of aerobic exercise, higher volumes of both aerobic and combined exercise improved some aspects of sleep quality during breast cancer chemotherapy. Exercise may be an attractive option to manage sleep dysfunction in cancer patients during chemotherapy.

Predictors of adherence to different types and doses of supervised exercise during breast cancer chemotherapy.

BACKGROUND: Exercise is beneficial for breast cancer patients during chemotherapy but adherence to different types and doses of exercise is a challenge. The purpose of this study was to examine predictors of adherence to different types and doses of exercise during breast cancer chemotherapy in a multicenter randomized controlled trial. METHODS: Breast cancer patients in Edmonton, Vancouver, and Ottawa, Canada receiving chemotherapy (N = 301) were randomized to a standard dose of 25-30 minutes of aerobic exercise (STAN), a higher dose of 50-60 minutes of aerobic exercise (HIGH), or a higher dose of 50-60 minutes of combined aerobic and resistance exercise (COMB). Predictors included demographic, medical, fitness, and quality of life variables. Exercise adherence was measured as the percentage of supervised exercise sessions completed. RESULTS: Overall adherence to the supervised exercise sessions was 73% (SD = 24%). In a multivariate regression model, six independent predictors explained 26.4% (p < 0.001) of the variance in exercise adherence. Higher exercise adherence was achieved by breast cancer patients in Vancouver (p < 0.001), with fewer endocrine symptoms (p = 0.009), randomized to STAN (p = 0.009), with fewer exercise limitations (p = 0.009), receiving shorter chemotherapy protocols (p = 0.015), and with higher VO2peak (p = 0.017). Disease stage (p for interaction = 0.015) and body mass index (p for interaction = 0.030) interacted with group assignment to predict adherence. For disease stage, patients with stage I/IIa disease adhered equally well to all three exercise interventions whereas patients with stage IIb/III disease adhered better to the STAN intervention than the two higher dose exercise interventions. For body mass index, healthy weight patients adhered equally well to all three exercise interventions whereas overweight patients adhered best to STAN and worst to COMB; and obese patients adhered best to STAN and worst to HIGH. CONCLUSIONS: Determinants of exercise adherence in breast cancer patients receiving chemotherapy are multidisciplinary and may vary by the exercise prescription.

Individual susceptibility to high altitude and immersion pulmonary edema and pulmonary lymphatics.

BACKGROUND: High-altitude pulmonary edema (HAPE) and immersion pulmonary edema (IPE) are potentially life-threatening conditions that affect athletes, including high-altitude climbers, long-distance swimmers, and underwater divers. The objectives of this study were to measure lung density (before and after exercise) and quantify the pulmonary lymphatic network in individuals susceptible and resistant to HAPE/IPE. METHODS: Eighteen male (N = 10) and female (N = 8) subjects were recruited. Based on medical histories, nine subjects were susceptible to HAPE/IPE, and nine were resistant. Subjects were matched for gender, age, height, weight, and cold-water diving or high-altitude trekking experiences. Lung mass and density (at three slice locations) were determined using computed tomography at rest and after intense exercise. Lung mass and density were calculated from X-ray attenuation values. Two blinded investigators counted interlobular septal lines according to criteria established by the research group. RESULTS: At rest, susceptible subjects had a lower lung density [Susceptible: 0.192 (0.035 SD) g ml 1'; Resistant: 0.22 (0.029 SD) g ml(-1))], a significantly lower lung mass [Susceptible: 132.1 (24.16 SD) g; Resistant: 156.1 (19.19 SD) g], and significantly fewer interlobular septa [Susceptible: 17 (4.5 SD); Resistant: 23 (7.1 SD)] compared to resistant subjects. The differences in density and mass were not affected by intense exercise. DISCUSSION: Subjects susceptible to HAPE/IPE had lower lung density, significantly lower lung mass, and fewer interlobular septa than subjects resistant to HAPE/IPE, suggesting a smaller pulmonary lymphatic network. The observed differences in lymphatics could represent either predisposing factors to, or sequelae of, these potentially lethal conditions.

Exercise-induced arterial hypoxaemia and the mechanics of breathing in healthy young women.

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension ( ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption ( ) = 49 ± 1, range 28-62 ml kg(-1) min(-1)) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (~85% ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation ( ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg(-1) min(-1)), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min(-1)), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism.

Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors.

PURPOSE: Fatigue is one of the most commonly reported side effects during treatment for breast cancer and can persist following treatment completion. Cancer-related fatigue after treatment is multifactorial in nature, and one hypothesized mechanism is cardiorespiratory and neuromuscular deconditioning. The purpose of this study was to compare cardiorespiratory and neuromuscular function in breast cancer survivors who had completed treatment and met the specified criteria for cancer-related fatigue and a control group of breast cancer survivors without fatigue. METHODS: Participants in the fatigue (n = 16) and control group (n = 11) performed a maximal exercise test on a cycle ergometer for determination of peak power, power at lactate threshold, and VO(2) peak. Neuromuscular fatigue was induced with a sustained submaximal contraction of the right quadriceps. Central fatigue (failure of voluntary activation) was evaluated using twitch interpolation, and peripheral fatigue was measured with an electrically evoked twitch. RESULTS: Power at lactate threshold was lower in the fatigue group (p = 0.05). There were no differences between groups for power at lactate threshold as percentage of peak power (p = 0.10) or absolute or relative VO(2) peak (p = 0.08 and 0.33, respectively). When adjusted for age, the fatigue group had a lower power at lactate threshold (p = 0.02) and absolute VO(2) peak (p = 0.03). There were no differences between groups in change in any neuromuscular parameters after the muscle-fatiguing protocol. CONCLUSIONS: Findings support the hypothesis that cardiorespiratory deconditioning may play a role in the development and persistence of cancer-related fatigue following treatment. Future research into the use of exercise training to reduce cardiorespiratory deconditioning as a treatment for cancer-related fatigue is warranted to confirm these preliminary findings.

Exercise-induced arterial hypoxemia in female masters athletes.

The purpose of the study was to characterize exercise induced arterial hypoxemia (EIAH) in female masters athletes (FMA). We hypothesized that FMA would experience EIAH during treadmill running. Eight FMA (48-57 years) completed pulmonary function testing and an incremental exercise test until exhaustion (V̇O2max⁡ = 45.7 ± 6.5, range:35-54 ml/kg/min). On a separate day, the participants were instrumented with a radial arterial catheter and an esophageal temperature probe. Participants performed three to four constant load exercise tests at 60-70 %, 75 %, 90 %, 95 %, and 100 % of maximal oxygen uptake while sampling arterial blood and recording esophageal temperature. We found that FMA decrease their partial pressure of oxygen (86.0 ± 7.6, range:73-108 mmHg), arterial saturation (96.2 ± 1.2, range:93-98 %), and widen their alveolar to arterial oxygen difference (23.2 ± 8.8, range:5-42 mmHg) during all exercise intensities however, with variability in terms of severity and pattern. Our findings suggest that FMA experience EIAH however aerobic fitness appears unrelated to occurrence or severity (r = 0.13, p = 0.756).

Respiratory physiology: adaptations to high-level exercise.

Most exercise scientists would agree that the physiological determinants of peak endurance performance include the capacity to transport oxygen to the working muscle, diffusion from the muscle to the mitochondria, energy production and force generation, all influenced by signals from the central nervous system. In general, the capacity of the pulmonary system far exceeds the demands required for ventilation and gas exchange during exercise. Endurance training induces large and significant adaptations within the cardiovascular, musculoskeletal and haematological systems. However, the structural and functional properties of the lung and airways do not change in response to repetitive physical activity and, in elite athletes, the pulmonary system may become a limiting factor to exercise at sea level and altitude. As a consequence to this respiratory paradox, highly trained athletes may develop intrathoracic and extrathoracic obstruction, expiratory flow limitation, respiratory muscle fatigue and exercise-induced hypoxaemia. All of these maladaptations may influence performance.