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.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

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.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Weight trajectories in women receiving systemic adjuvant therapy for breast cancer.

BACKGROUND: Weight gain after breast cancer (BC) diagnosis is a well-known phenomenon; however, it is not a universal phenomenon and identification of patients at highest risk for weight gain is needed. This study investigates weight trajectories in early BC patients at 2 years post-primary treatment, examining potential contributing factors such as age, race, and receipt of chemotherapy, anti-HER-2 therapy, and endocrine treatment (ET). METHODS: A single institution cohort of newly diagnosed women age 21 and older with early breast cancer patients (Stage 0-3) were identified by retrospective chart review (diagnosis year 1995 to 2016). Log-binomial regression models for net weight changes at 2 years post-primary treatment including patient demographic, clinical, and treatment characteristics. RESULTS: The final sample of 625 patients included 29% who were non-White and 37% who were pre-menopausal at diagnosis. Body mass index (BMI) at diagnosis was calculated and found to be normal in 33% (BMI 18 to < 25), overweight in 27% (BMI 25 to < 30), and obese in 40% (BMI 30 and higher). At 2 years, compared to weight at diagnosis, 31% had lost > 2 kg, 34% had stable weight ± 2 kg, and 35% had gained > 2 kg. Factors associated with > 2 kg weight gain were menopausal status (pre-menopausal HR 1.65, 95% CI 1.34-2.04, p < .0001), receiving any chemotherapy (HR 1.36, 95% CI 1.04-1.77), and anthracycline-based chemotherapy followed by ET (HR 1.60, CI 1.01-2.45). Anti-HER-2 therapy and transition from pre- to post-menopausal during the 2-year study period were not significant factors in weight gain. In multivariate analysis, menopausal status remained the only significant variable related to weight gain when adjusted for treatment. For all treatment combinations, pre-menopausal women had significantly more weight gain. CONCLUSIONS AND RELEVANCE: Weight gain, weight loss, and stable weight in women with early breast cancer vary greatly by treatment plan. However, pre-menopausal patients have the highest risk for weight gain.

Weight-Related Communications Between Oncology Clinicians and Women With Obesity at Early Breast Cancer Diagnosis: Findings From a Review of Electronic Health Records.

Background: The American Society of Clinical Oncology (ASCO) Position Statement on Obesity and Cancer notes that the oncology care team is in a unique position to initiate weight management conversations that may help patients manage their weight in survivorship.Methods: Qualitative and quantitative content analysis of electronic health records at a university-affiliated cancer hospital was conducted to gather documentation of weight-related communications between oncology clinicians and their patients with obesity (Body Mass Index 30 or higher) at early breast cancer diagnosis.Results: The sample includes 237 women, mean age 56.5 (range 25-86), 37% black, and mean BMI 36 (range 30-59). Ninety-three patients (39%) had weight-related communications with at least one oncology clinician, for a total of 120 communications. Seventy-three percent of these communications were with a medical oncologist, 17% with a radiation oncologist, and 10% with a surgical oncologist. Examples of communications include referrals to weight management programs (22%), printed patient instructions about diet or diet and exercise (12%), and clinician notes describing weight-related interactions with their patients (67%).Conclusions: This study provides preliminary but encouraging evidence of weight-related communications during a busy clinic visit with patients who were obese at breast cancer diagnosis.

Patient-reported and clinician-reported chemotherapy-induced peripheral neuropathy in patients with early breast cancer: Current clinical practice.

BACKGROUND: In the current study, the authors investigated the incidence of moderate to severe chemotherapy-induced peripheral neuropathy (CIPN) for chemotherapy regimens commonly used in current clinical practice for the treatment of patients with early breast cancer. Patient-reported and clinician-assessed CIPN severity scores were compared, and risk factors for CIPN severity were identified. METHODS: Patients completed a Patient-Reported Symptom Monitoring form and oncologists completed a Common Terminology Criteria for Adverse Events form. CIPN reports were collected prospectively during regularly scheduled infusion visits throughout the duration of chemotherapy. RESULTS: The sample included 184 women with a mean age of 55 years; approximately 73% were white. The 4 chemotherapy regimens used were doxorubicin and cyclophosphamide plus paclitaxel (60 patients); docetaxel and cyclophosphamide (50 patients); docetaxel, carboplatin, and anti-human epidermal growth factor receptor 2 (HER2) (24 patients); and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin (18 patients). All patients treated with doxorubicin and cyclophosphamide plus paclitaxel and doxorubicin and cyclophosphamide plus paclitaxel and carboplatin received paclitaxel; all patients treated with docetaxel and cyclophosphamide and docetaxel, carboplatin, and anti-HER2 received docetaxel. The chemotherapy dose was reduced in 52 patients (28%); in 15 patients (29%), this reduction was due to CIPN. Chemotherapy was discontinued in 26 patients (14%), 8 because of CIPN. Agreement between patient-reported and clinician-assessed CIPN severity scores was minimal (weighted Cohen kappa, P = .34). Patient-reported moderate to severe CIPN was higher for paclitaxel (50%) compared with docetaxel (17.7%) (P < .001). Pretreatment arthritis and/or rheumatism (relative risk [RR], 1.58; 95% CI, 1.06-2.35 [P = .023]) and regimens containing paclitaxel (RR, 2.88; 95% CI, 1.72-4.83 [P < .0001]) were associated with higher CIPN severity. Being married (RR, 0.57; 95% CI, 0.37-0.887 [P = .01]) was found to be associated with lower CIPN severity. CONCLUSIONS: The discrepancy between patient-reported and clinician-assessed CIPN underscores the need for both patient and clinician perspectives regarding this common, dose-limiting, and potentially disabling side effect of chemotherapy.

Patient-Reported Toxicities During Chemotherapy Regimens in Current Clinical Practice for Early Breast Cancer.

BACKGROUND: This study explores the incidence of patient-reported major toxicity-symptoms rated "moderate," "severe," or "very severe"-for chemotherapy regimens commonly used in early breast cancer. PATIENTS AND METHODS: Female patients aged 21 years or older completed a validated Patient-Reported Symptom Monitoring instrument and rated 17 symptoms throughout adjuvant or neoadjuvant chemotherapy. Fisher's exact tests compared differences in percentages in symptom ratings, and general linear regression was used to model the incidence of patient-reported major toxicity. RESULTS: In 152 patients, the mean age was 54 years (range, 24-77), and 112 (74%) were white; 51% received an anthracycline-based regimen. The proportion of patients rating fatigue, constipation, myalgia, diarrhea, nausea, peripheral neuropathy, and swelling of arms or legs as a major toxicity at any time during chemotherapy varied significantly among four chemotherapy regimens (p < .05). The mean (SD) number of symptoms rated major toxicities was 6.3 (3.6) for anthracycline-based and 4.4 (3.5) for non-anthracycline-based regimens (p = .001; possible range, 0-17 symptoms). Baseline higher body mass index (p = .03), patient-reported Karnofsky performance status ≤80 (p = .0003), and anthracycline-based regimens (p = .0003) were associated with greater total number of symptoms rated major toxicities (alternative model: chemotherapy duration, p < .0001). Twenty-six percent of dose reductions (26 of 40), 75% of hospitalizations (15 of 20), and 94% of treatment discontinuations (15 of 16) were in anthracycline-based regimens. CONCLUSION: Capturing multiple toxicity outcomes throughout chemotherapy enables oncologists and patients to understand the range of side effects as they discuss treatment efficacies. Continuous symptom monitoring may aid in the timely development of interventions that minimize toxicity and improve outcomes. IMPLICATIONS FOR PRACTICE: This study investigated patient-reported toxicities for 17 symptoms recorded prospectively during adjuvant and neoadjuvant chemotherapy regimens for early breast cancer. An analysis of four commonly used chemotherapy regimens identified significant differences among regimens in both individual symptoms and total number of symptoms rated moderate, severe, or very severe. Longer chemotherapy regimens, such as anthracycline-based regimens followed by paclitaxel, had higher proportions of symptoms rated major toxicities. The inclusion of patient perspectives on multiple toxicity outcomes at the same time at multiple time points during chemotherapy has the potential for improving patient-provider communication regarding symptom management, patient satisfaction, and long-term clinical outcomes.

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.

Weight gain in hormone receptor-positive (HR+) early-stage breast cancer: is it menopausal status or something else?

PURPOSE: This study investigates weight trajectories in pre- versus postmenopausal breast cancer (BC) survivors diagnosed with hormone receptor-positive tumors, with a specific focus on discerning menopausal status and type of endocrine treatment (ET) as risk factors for weight gain during ET. METHODS: We conducted a retrospective review of electronic medical records. Descriptive statistics and Chi-squared and t tests were used to compare pre- and postmenopausal women. Chi-squared tests and ANOVA were used for within-group associations between patient characteristics and weight trajectories. Log-binomial regression models were used to estimate relative risk for weight gain. RESULTS: The final sample was 32% premenopausal (n = 140) and 68% postmenopausal (n = 298). Relative risk (RR) for weight gain during ET was highest in women who were premenopausal (RR = 1.29, 1.03-1.52) and had Stage 3 BC (RR = 2.12, 1.59-2.82), mastectomy (RR = 1.49, 1.19-1.88), axillary node dissection (RR = 1.39, 1.11-1.73), and chemotherapy (RR = 1.80, 1.37-2.36). For each kg of weight gained between BC diagnosis and start of ET, and for each additional year of age, RR of gaining weight during ET decreased (RR = 0.98, 0.97-0.99, and RR = 0.99, 0.98-0.99, respectively). Menopausal status and type of ET were not significant predictors of weight gain. In multivariable analysis, only weight loss between BC diagnosis and start of ET was significant. CONCLUSION: The association of weight loss prior to ET and subsequent substantial weight gain during ET warrants further investigation.

Weight changes in postmenopausal breast cancer survivors over 2 years of endocrine therapy: a retrospective chart review.

PURPOSE: Obesity and weight gain after breast cancer (BC) diagnosis can affect cancer outcomes. This study explores the question of weight change during the first 2 years of endocrine treatment (ET) to identify the independent effects of BC diagnosis and treatment on post-diagnosis weight trajectories in early-stage postmenopausal BC survivors. METHODS: The study design is a retrospective chart review. Chi square tests and ANOVA were used to compare patients who gained >2 kg, lost >2 kg, or had stable weight. Log-binomial regression models were used to evaluate associations between patient characteristics and weight trajectories. RESULTS: The final sample is N = 300, with mean age at BC diagnosis of 65 years and 76% white. After 2 years of ET, 39% of study participants had gained >2 kg, 27% had lost >2 kg, and 34% had stable weight. Relative risks (RR) for weight gain were as follows: age at diagnosis = 0.98 (0.96, 0.99), being married = 1.48 (1.04, 2.12), weight change between BC diagnosis and start of ET = 0.98 (0.97, 0.99), Stage II = 1.42 (1.01, 2.01) or Stage III = 1.99 (1.41, 2.82), PR negative = 0.70 (0.51, 0.96), HER2 positive = 1.51 (1.07, 2.13), mastectomy = 1.49 (1.12, 1.98), axillary node dissection = 1.67 (1.27, 2.20), adjuvant chemotherapy = 1.49 (1.02, 2.19), and neoadjuvant chemotherapy = 2.29 (1.67, 3.14). Type of ET (tamoxifen or aromatase inhibitor) was not significant. CONCLUSIONS: In our sample of postmenopausal early-stage BC survivors, a majority had stable or lost weight during the first 2 years of ET. Higher disease complexity and associated treatment posed higher RR for weight gain.

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.

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-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.

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.

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.

Twenty-five years of research on the effects of exercise training in breast cancer survivors: A systematic review of the literature.

AIM: To investigate the role of exercise training the past 25 years on major physiological-psychological outcomes studied thus far in this patient population. METHODS: PubMed, MedlinePlus, the Cochrane Library, Web of Science, SportDiscus, Embase, Scorpus, and Google Scholar were searched from September to November 2013 to identify exercise training studies that used objective measurements of fitness and/or patient reported outcomes assessed pre and post-exercise training with statistical analyses performed in at least one of the following outcome measurements: Cardiorespiratory function, body composition, muscular strength, fatigue, depression, and overall quality of life. Five reviewers independently identified the studies that met the criteria for the review and discrepancies were resolved by consensus among all authors. RESULTS: Fifty-one studies were included in this review with 5 from the period between 1989-1999, 11 from 2000-2006, and 35 from 2007-2013. The evolution of study designs changed from aerobic only exercise training interventions (1989-1999), to a combination of aerobic and resistance training (2000-2006), to studies including an arm of resistance training or examining the effects of resistance training as the main mode of exercise (2007-2013). Overall, the benefits of exercise showed improvements in cardiorespiratory function, body composition, strength, and patient reported outcomes including fatigue, depression, and quality of life. CONCLUSION: Exercise training appears to be safe for most breast cancer patients and improvements in physiological, psychological, and functional parameters can be attained with regular participation in moderate intensity exercise.