Effect of physical exercise on immune, inflammatory, cardiometabolic biomarkers, and fatty acids of breast cancer survivors: results from the MAMA_MOVE Gaia After Treatment trial.

PURPOSE: Physical exercise has positive effects on clinical outcomes of breast cancer survivors such as quality of life, fatigue, anxiety, depression, body mass index, and physical fitness. We aimed to study its impact on immune, inflammatory, cardiometabolic, and fatty acids (FA) biomarkers. METHODS: An exploratory sub-analysis of the MAMA_MOVE Gaia After Treatment trial (NCT04024280, registered July 18, 2019) was performed. Blood sample collections occurred during the control phase and at eight weeks of the intervention phase. Samples were subjected to complete leukocyte counts, cytokine, and cardiometabolic marker evaluation using flow cytometry, enzyme-linked immunoassays, and gas chromatography. RESULTS: Ninety-three percent of the 15 participants had body mass index ≥ 25 kg/m2. We observed a decrease of the plasmatic saturated FA C20:0 [median difference - 0.08% (p = 0.048); mean difference - 0.1 (95%CI - 0.1, - 0.0)], positively associated with younger ages. A tendency to increase the saturated FA C18:0 and the ratio of unsaturated/saturated FA and a tendency to decrease neutrophils (within the normal range) and interferon-gamma were observed. CONCLUSIONS: Positive trends of physical exercise on circulating immune cells, inflammatory cytokines, and plasmatic FA were observed. Larger studies will further elucidate the implications of physical exercise on metabolism. These exploratory findings may contribute to future hypothesis-driven research and contribute to meta-analyses.

Exercise Training Benefits Health-Related Quality of Life and Functional Capacity during Breast Cancer Chemotherapy: A Randomized Controlled Trial.

PURPOSE: To examine the effectiveness of a supervised exercise training program (SETP) on health-related quality of life (HRQoL) and functional capacity in women with breast cancer (BC) undergoing chemotherapy. METHODS: Ninety-three women with early-stage BC were randomly allocated to a SETP plus usual care (exercise, n = 47) or usual care alone (UC, n = 46). The SETP included three sessions per week, combining aerobic and resistance training, conducted concurrently over the chemotherapy. The EORTC Cancer Quality-of-Life-Questionnaire-Core-30 (QLQ-C30) and the BC-specific module (QLQ-BR23) were used to assess HRQoL. Functional capacity was analyzed by maximum voluntary handgrip strength (MVHS) and by the 30-s chair sit-to-stand test (30-s CST). These endpoints were assessed at baseline (t0); middle (t1; after 8 or 12 wk of t0); and at the end of chemotherapy (t2; after 20 wk of t0). Mean changes from baseline were assessed by an intention-to-treat approach. RESULTS: Mixed linear model analyses showed that Exercise group experienced less deterioration in several domains of QLQ-C30 at t2, including in global health status/QoL (Δ = 9.39 units; P = 0.034), QLQ-C30 summary score (Δ = 8.08 units; P < 0.001), physical (Δ = 15.14 units; P < 0.001), role ( Δ = 21.81 units; P < 0.001), cognitive (Δ = 9.16 units; P = 0.032) and social functioning (Δ = 11.67 units; P = 0.038), compared with the UC group. Similarly, Exercise group exhibited significant lower levels of fatigue (Δ = -20.19 units; P < 0.001) and appetite loss (Δ = -13.69 units; P = 0.034), compared with the UC group. Significant between-group differences were observed on MVHS of the tumor/surgery upper limb side (Δ = 2.64 kg; P < 0.001) and contralateral limb (Δ = 2.22 kg; P < 0.001), and on the 30-s CST score (Δ = 3.56repetitions; P < 0.001), favoring the Exercise group. No differences were observed on QLQ-BR23 domains. CONCLUSIONS: Exercise training was an effective complementary therapy to prevent the deterioration of HRQoL and functional capacity during chemotherapy in women with early-stage BC.

Effects of a Physical Exercise Program on Quality of Life and Physical Fitness of Breast Cancer Survivors: the MAMA_MOVE Gaia After Treatment Trial.

To assess the effects of a group class physical exercise program on health-related quality of life (HRQOL), physical fitness and activity, and safety in early breast cancer women after treatment, a double-phase trial [16-week control phase (CP) followed by a 16-week intervention phase (IP)] was designed. Outcomes were evaluated at baseline (T1), 8 (T2) and 16 (T3) weeks (CP), and 24 (T4) and 32 (T5) weeks (IP). The primary endpoint was global health status. Out of 82 enrolled patients, 37 completed the IP. Global health status decreased (-10,1; 95% CI -19.8 to -0.4; p = 0.040) during the CP and stabilized during the IP. Physical and sexual functioning increased during the IP (p = 0.008; p = 0.017), while cardiorespiratory fitness increased in the CP (p = 0.004). Upper limb strength and lower limb functionality increased during both phases [CP: p < 0.0001, p = 0.001 (surgical and nonsurgical arm), p = 0.028; IP: p < 0.0001, p = 0.002, p = 0.009]. Body mass index decreased in the IP (p = 0.026). Waist circumference increased in the CP (p = 0.001) and decreased in the IP (p = 0.010); sedentary behaviours and moderate and vigorous physical activity did not change. Adherence to 70% of the sessions was reported in 54% of patients. No serious adverse events related to the intervention were reported. In conclusion, the physical exercise program was able to prevent the decline in global health status and to improve other domains of HRQOL and physical fitness. As physical exercise is not the standard of care in many countries, the implementation of group class programs might be an option.

Effects of walking football on adherence, safety, quality of life and physical fitness in patients with prostate cancer: Findings from the PROSTATA_MOVE randomized controlled trial.

Aims: To analyze the feasibility and impact of a walking football (WF) program on quality of life (QoL), cardiorespiratory fitness (CRF), muscle strength, and balance program in men with prostate cancer under androgen deprivation therapy (ADT). Methods: Fifty patients with prostate cancer (stages IIb-IVb) under ADT were randomized to a 16-week WF program plus usual care (n=25) or usual care control group (n=25). The WF program consisted of three 90-minute sessions per week. Recruitment, withdrawal, adherence, enjoyment rate, and safety of the intervention were recorded throughout the study. Cardiorespiratory fitness was assessed before and after the interventions, while handgrip strength, lower limb muscle strength, static balance, and QoL were assessed before, during (week 8), and after (week 16) the interventions. Adverse events during sessions were also recorded. Results: The WF group showed high levels of adherence (81.6 ± 15.9%) and enjoyment rate (4.5 ± 0.5 out of 5 points). In the intention-to-treat analysis, the WF group showed an improvement in chair sit-to-stand (p=0.035) compared to the control group. Within-group comparisons showed that handgrip strength in the dominant upper limb (p=0.024), maximal isometric muscle strength in the non-dominant lower limb (p=0.006), and balance in the dominant limb (p=0.009) improved over time in the WF group but not in the usual care group. The results obtained from the per-protocol analysis indicate that CRF improved significantly in the WF group as compared to the control group (p=0.035). Within-group analysis revealed that CRF (p=0.036), muscle strength in dominant (p=0.006) and non-dominant (p=0.001) lower limbs, and balance in the non-dominant lower limb (p=0.023) improved after 16 weeks of WF, but not in the control group. One major traumatic injury (muscle tear) was reported with a complete recovery before the end of the intervention. Conclusion: This study suggests that WF is feasible, safe, and enjoyable in patients with prostate cancer under hormonal therapy. Furthermore, patients who adhere to the WF program can expect cardiorespiratory fitness, muscle strength, and balance improvements. Clinical trials registration: clinicaltrials.gov, identifier NCT04062162.

Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial.

AIMS: Exercise training has been suggested to prevent anthracycline-related cardiac dysfunction, but clinicalbased evidence is scarce. We investigated the effects of a supervised exercise training programme (SETP) on cardiac toxicity markers in women with breast cancer (BC) receiving anthracycline-containing chemotherapy. METHODS AND RESULTS: Ninety-three women with early-stage breast cancer were randomly allocated to a supervised exercise training programme (SETP) plus usual care group (Exercise, n = 47) or usual care alone group (UC, n = 46). The SETP consisted of three sessions per week, combining aerobic and resistance training, conducted concurrently across the anthracycline-containing chemotherapy length. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to the end of anthracycline cycles. Secondary endpoints included global longitudinal strain (GLS) and other conventional echocardiographic parameters, cardiorespiratory fitness (estimated peak VO2), circulating biomarkers (NT-proBNP, hs-TnT), and safety of the SETP. The study endpoints were also assessed 3 months after the end of anthracycline cycles. All patients were prescribed four cycles of doxorubicin plus cyclophosphamide (AC). No significant between-group differences in LVEF change were seen at the end of AC [mean difference: 0.7%; 95% confidence interval (CI): -0.8, 2.3; P = 0.349] and 3 months after AC (1.1%; 95% CI: -0.5, 2.6; P = 0.196). Compared to the usual care (UC) group, the estimated peak VO2 increased in the Exercise group at the end of AC (1.6 mL O2·kg-1·min-1; 95% CI: 0.06, 3.1; P = 0.041) and 3 months after AC (3.1 mL O2·kg-1·min-1; 95% CI: 1.4, 4.7; P < 0.001). No between-group differences were found in the remaining secondary endpoints. No serious adverse events were observed during SETP. CONCLUSION: Exercise training was safe during chemotherapy and significantly improved cardiorespiratory fitness. No significant effects were seen on cardiac toxicity markers (LVEF or GLS) as compared to the usual care. TRIAL REGISTRATION: Mama Move Gaia on treatment trial ISRCTN32617901.

Breast cancer patients are often treated with chemotherapy. Despite the clinical benefit, some of these drugs increase the risk of cardiac toxicity and impair patients' cardiorespiratory fitness. Exercise training has been proposed as a preventive approach, but clinical-based evidence is scarce. The results of this trial showed that an exercise training programme, combining aerobic training and resistance training, conducted during chemotherapy, did not significantly attenuate the decline in conventional cardiac function parameters when compared to usual care. However, the results of this trial showed that the training programme was safe and significantly improved cardiorespiratory fitness.

Effects of physical exercise on outcomes of cardiac (dys)function in women with breast cancer undergoing anthracycline or trastuzumab treatment: study protocol for a systematic review.

BACKGROUND: Cardiotoxicity is a known complication and one of the most adverse effects from the use of conventional treatments such as anthracyclines and trastuzumab in breast cancer (BC) care. This phenomenon has been associated with the restriction of therapeutic options and the increase of cardiovascular complications, which may compromise the survival of patients. Implementation of preventive strategies is an important approach for the management of this issue. Physical exercise has been proposed as a non-pharmacological strategy to counteracting cardiotoxicity. The aim of this protocol is to describe the rationale and methods for a systematic review of published randomized controlled trials (RCTs) that have analysed the effects of physical exercise on outcomes of cardiac (dys)function in women with BC undergoing neoadjuvant or adjuvant treatment containing anthracyclines and/or trastuzumab. METHODS AND ANALYSIS: This is a protocol for a systematic review reported according to the PRISMA-P 2015 checklist. Randomized controlled trials (RCTs) will be included. The literature will be screened on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus. The risk of bias of the included RCTs will be assessed using the Cochrane Collaboration's tool. The primary outcomes will be systolic function (left ventricular ejection fraction), diastolic function (E/A' ratio, deceleration time of early left ventricular filling, isovolumetric relaxation time, E/E' septal and lateral ratio) and myocardial deformation imaging outcomes (strain and strain rate [measured in longitudinal, radial, or circumferential directions]). Secondary outcomes will be cardiac biomarkers (troponin I or T, high-sensitivity troponin I or T, brain natriuretic peptide, amino terminal of B-type natriuretic peptide). Data will be descriptively reported, and quantitative synthesis will also be considered if the included studies are sufficiently homogenous. DISCUSSION: This systematic review will help to understand the effectiveness of physical exercise on counteracting cardiotoxicity related to anticancer therapies in women with BC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096060.

Impact of exercise training on cardiotoxicity and cardiac health outcomes in women with breast cancer anthracycline chemotherapy: a study protocol for a randomized controlled trial.

BACKGROUND: Anthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although it improves disease-free and overall survival, the use of anthracyclines is associated with a cumulative risk of cardiac toxicity. Preventive strategies to optimize cardiac health are needed and exercise is proposed as a potential non-pharmacological approach for counteracting anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT are from animal studies, with only a few studies in a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in the mitigation of ARC, clinical, real-world trials claim require a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample and investigate cardiac function through serial measures of biomarkers and imaging techniques. METHODS: This protocol describes a two-arm, prospective, randomized controlled trial that will explore the cardioprotective effect of a structured exercise program in women with BC undergoing anthracycline-containing chemotherapy (ACT). Ninety adult women with early BC and recommended to receive ACT will be randomly assigned (1:1) to an intervention group or a control group. Patients allocated to the intervention group will perform a supervised exercise program three times per week, consisting of a combination of aerobic and resistance training with progressive intensity and volume, during the time period they receive ACT. The control group will receive standard BC care. Primary outcomes related to cardiac (dys)function will be circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, resting left ventricular (LV) longitudinal strain, and resting LV ejection fraction. Secondary outcomes will include the assessment of resting blood pressure, resting heart rate (HR), resting HR variability (HRV), recovery HR, physical function outcomes, self-reported physical activity level, health-related quality of life, and fatigue. Data will be obtained at baseline (t0), after the end of anthracycline-treatment (t2), and 3 months after t2 (t3). Additionally, NT-proBNP will be measured 1-24 h prior to each anthracycline-treatment cycle (t1). DISCUSSION: The implementation of the present study design, using novel clinical biomarkers, will determine the effect of structured exercise interventions at mitigating ARC, with the overall aim of finding means to further improve BC care. TRIAL REGISTRATION: ISRCTN, ISRCTN32617901 . Registered on 24 October 2018. Last updated on 11 January 2019.

Ferric Carboxymaltose in the treatment of chemotherapy-induced anaemia: an effective, safe and cost- sparing alternative to blood transfusion.

Anaemia is highly prevalent in cancer patients, adversely affects quality of life and impacts survival. The pathogenesis is multifactorial, with iron deficiency being a major and potentially treatable contributor. This study aimed to assess the effectiveness and economic impact of ferric carboxymaltose in chemotherapy-induced anaemia. This prospective cohort study between 2015-2016 of chemotherapy-treated patients for solid tumours, grade ≥2 anaemia and iron deficiency evaluated hematopoietic response four weeks after ferric carboxymaltose treatment. Transfusion rate of all cancer patients treated at our ambulatory unit during the two-year study period (2015-2016) was compared to a retrospective cohort (2013-2014) who received blood transfusion only. Between 2015-2016, 99 patients were included and treated with ferric carboxymaltose, the majority of whom (n = 81) had relative iron deficiency. Mean haemoglobin concentrations improved from 9.2 [6.7-10.8] g/dL to 10.6 [7.8-14.2] g/dL four weeks after treatment. A 26% reduction in the transfusion rate was observed from control retrospective to the prospective study group including ferric carboxymaltose treated patients [relative risk 0.74 (95% CI:0.66-0.83)]. The cost analysis showed a benefit for the use of ferric carboxymaltose in chemotherapy-induced anaemia. This study shows that ferric carboxymaltose is an effective, cost-saving support treatment, reducing the need for allogeneic transfusions saving blood units which are a limited resource.