Breast Cancer Exercise Research Articles

The Benefits of Exercise in Breast Cancer.

Breast cancer is the most prevalent cancer among women, accounting for nearly 30% of all cancers, while in men, it represents only 1% of cases. Breast cancer is the main cause of death for cancer, and its incidence and mortality vary according to patients' ethnicity, geographic region, and socioeconomic status. Due to the low prevalence of breast cancer among men and the scarcity of studies in the literature, exercises have been prescribed based on extrapolations from studies on female patients. Scientific evidence has suggested beneficial effects of physical exercises on breast cancer prevention, treatment, and post-treatment. In addition to combatting sedentary behavior, it is essential to maintain a healthy body weight, limit alcohol consumption, and follow a balanced diet, rich in fruit, vegetables, grains and fibers, and limited in red meat. The effects of exercises are not restricted to breast cancer, but extend to controlling modifiable risk factors, and reducing the incidence of cardiovascular diseases, and all-cause and cardiovascular mortality.

Body composition changes in a 12-week exercise intervention for breast cancer patients.

e12500 Background: Evidence has linked weight gain and obesity to increased breast cancer risk, poorer outcomes, decreased survivorship, and increased risk of recurrence. Adjuvant therapies can increase weight gain, making tailored exercise interventions beneficial in maintaining a healthy weight. In this study, body composition changes were examined after a 12-week exercise program in a cohort of breast cancer survivors. Methods: The Breast Cancer Exercise Rehabilitation Research Study recruited breast cancer survivors to undergo a 12-week exercise program (NCT04013568) and examine body composition changes. Measurements taken included anthropometry (waist circumference, waist-to-hip ratio, BMI), DXA body composition measurements (fat mass-visceral and subcutaneous, trunk to limb, muscle mass-appendicular, and whole body), and BIA (Bio-electrical Impedance Analysis-muscle, fat, and water). 34 participants completed the exercise program and baseline and post-12-week measurements were obtained. Descriptive statistics and a paired t-test analysis was done to analyze changes in body composition using SAS onDemand. A correlation analysis between measurements simple to do in clinic and DXA measurements were run to determine proxy use for DXA. Results: After a 12-week exercise program, reductions in body fat via DXA scan, BIA, and InBody (whole body fat, whole body fat %, trunk fat, leg fat, body fat %, hip width at maximum girth, body fat mass, and percent body fat) were observed. Additionally, increases in lean mass (Appendicular Lean Mass (ALM)/height2, Appendicular Lean/height2, ALM index, and lean body mass), whole body mass measured by DXA, basal metabolic rate, water retention (extracellular water and total body water), and skeletal muscle mass were observed. Correlation analysis revealed BMI can be used as a surrogate measure for whole body mass measured by DXA (r=0.91, p<0.001) and can be utilized to measure change over time. Skinfold sum showed moderate correlation for measuring subcutaneous fat mass by DXA (r=0.45, p=0.0096). Conclusions: In our population of breast cancer survivors, a 12-week exercise program did show various changes in body composition according to InBody, DXA, and BIA measurements. DXA and InBody measurements were feasible, making it readily available for patients. Additionally, simple measures such as BMI and skinfold sum showed moderate to strong correlation with DXA measurements, validating use of these measurements in routine practice. Clinical trial information: NCT04013568. [Table: see text]

Regulation of the Effect of Physical Activity Through MicroRNAs in Breast Cancer.

Physical activity and exercise can induce beneficial molecular and biological regulations that have been associated with an incidence of various diseases, including breast cancer. Recent studies demonstrated that the potential links between physical activity-induced circulating microRNAs (miRNAs) and cancer risk and progression. Here, we investigated whether altered miRNAs by exercise could influence breast cancer progression. After primary searching in PubMed and reviewing the full-text papers, candidate miRNAs altered by exercise in breast cancer were identified. Analysis of expression profiles and clinical outcomes of altered miRNAs using The Cancer Genome Atlas datasets showed altered miRNAs expressions were significantly associated with the patient's prognosis, whereas prognostic values of each miRNA varied in different stages and subtypes. In addition, altered miRNAs profiles regulated various target genes and key signaling pathways in tumorigenesis, including pathways in cancer and the PI3K-Akt signaling pathway; however, miRNAs regulated the expression of target genes differently according to tumor stages and subtypes. These results indicate that circulating miRNAs are promising noninvasive stable biomarkers for early detection, diagnosis, prognosis, and monitoring the response to clinical therapies of breast cancer. Moreover, stages and subtype-stratified approaches for breast cancer progression would be needed to evaluate the prognostic value of miRNAs for biomarkers and therapeutic targets.

The Importance Of Physical Exercise In Cardiorespiratory Fitness In Active Breast Cancer Patients

In the last ten years, there has been a strong and increasing interest in the role of physical exercise in breast cancer (BC) patients demonstrating that physical exercise may control and reduce treatments side effects improving their quality of life, reducing fatigue and depression levels, improving their cardiorespiratory fitness (CRF), functional capacity and strength. CRF is a value associated with better survival in BC patients. However, there is no knowledge about if active survivors could achieve similar values of CRF than active healthy women and the impact of a sedentary behaviour in these groups of women. PURPOSE: To stablish the role of physical exercise in CRF measured by V02 max in active breast cancer women (Act-BCW) compared to healthy women (HW) METHODS: Ninety two women were divided in four different groups: sedentary breast cancer women (Sed-BCW), active breast cancer women (Act-BCW), sedentary healthy women (Sed-HW) and active healthy women (Act-HW). All of them carried out a battery of six physical test. RESULTS: In terms of VO2, it was observed significant differences between all the groups (p < 0,05) except Act-HW and Act-BCW. (0,753). V02 values were: 42,11 ± 3,63 (Act-BCW), 36,26 ± 4,46 (Sed-BCW) 41,69 ± 4,31 (Act-HW) 34,56 + 5,72 (Sed-HW). Means differences, CI 95% and significance are shown in table 1.Table 1. Mean differences, CI 95% and significance in VO2 between groups.CONCLUSIONS: Act-BCW could achieve same values in V02 max that Act-HW, but also, they could achieve even higher values. For this reason, it is crucial to promote the practice of physical activity in breast cancer patients, (at least 150 minutes/week) because their fitness capacity improves considerably, and this is related with better survival.

Real-time exercise reduces impaired cardiac function in breast cancer patients undergoing chemotherapy: A randomized controlled trial.

Previous studies have reported that chemotherapy results in substantial long-term risk of heart failure. Exercise ameliorates exercise responses and exercise tolerance in patients receiving chemotherapy. The cardioprotective effect of real-time exercise in breast cancer is still unclear. The aim of the present study was to determine the effect of real-time moderate-to-high-intensity exercise training in women with breast cancer undergoing chemotherapy and to follow up on parameters of cardiac function and exercise capacity at different times. We hypothesized that early moderate-to-high-intensity exercise training has beneficial effects on cardiac function in women with breast cancer undergoing chemotherapy. This was a randomized controlled study that included 32 women randomly allocated into the control or exercise group. Exercise began with the first cycle of chemotherapy, and the training program was maintained during chemotherapy with 2 to 3 sessions per week for 3 months. Patients were instructed to perform moderate-to-high-intensity training with aerobic and resistance training. Outcome measurements were echocardiography and cardiopulmonary exercise test. The primary outcome was the change in left ventricle ejection fraction (LVEF). The secondary outcome was peak oxygen consumption (peak VO2). The control group showed lower cardiac systolic function than the exercise group [mean (SD) LVEF 62% (2) and 70% (5), P<0.05], reduced cardiac diastolic function, and cardiac hypertrophy at 3, 6 and 12 months after chemotherapy. At 6 months after chemotherapy, the exercise group exhibited relatively higher exercise capacity than controls [mean (SD) VO2 12.1 (2.2) and 13.6 (2.2) mL/kg/min, P<0.05]. The main effect size of the study based on echocardiography outcomes was 0.25 (95% confidence interval 0.23 to 0.27), a medium effect size. Moderate-to-high-intensity exercise training in breast cancer patients undergoing chemotherapy may prevent impaired cardiac function. https://www. in.th (Identifier TCTR20190330002).

Exercise as a diagnostic and therapeutic tool for preventing cardiovascular morbidity in breast cancer patients\u2013 the BReast cancer EXercise InTervention (BREXIT) trial protocol

BackgroundAnthracycline chemotherapy (AC) is an efficacious (neo) adjuvant treatment for early-stage breast cancer (BCa), but is associated with an increased risk of cardiac dysfunction and functional disability. Observations suggest that regular exercise may be a useful therapy for the prevention of cardiovascular morbidity but it is yet to be interrogated in a large randomised trial.The primary aims of this study are to: 1) determine if 12-months of ET commenced at the onset of AC can reduce the proportion of BCa patients with functional disability (peak VO2, < 18 ml/kg/min), and 2) compare current standard-of-care for detecting cardiac dysfunction (resting left-ventricular ejection fraction assessed from 3-dimensional echocardiography) to measures of cardiac reserve (peak exercise cardiac output assessed from exercise cardiac magnetic resonance imaging) for predicting the development of functional disability 12-months following AC. Secondary aims are to assess the effects of ET on VO2peak, left ventricular morphology, vascular stiffness, cardiac biomarkers, body composition, bone mineral density, muscle strength, physical function, habitual physical activity, cognitive function, and multidimensional quality of life.MethodsOne hundred women with early-stage BCa (40–75 years) scheduled for AC will be randomized to 12-months of structured exercise training (n = 50) or a usual care control group (n = 50). Participants will be assessed at baseline, 4-weeks following completion of AC (4-months) and at 12-months for all measures.DiscussionWomen diagnosed with early-stage BCa have increased cardiac mortality. More sensitive strategies for diagnosing and preventing AC-induced cardiovascular impairment are critical for reducing cardiovascular morbidity and improving long-term health outcomes in BCa survivors.Trial registrationAustralia & New Zealand Clinical Trials Registry (ANZCTR), ID: 12617001408370. Registered on 5th of October 2017.

Effects of Aerobic Exercise on Cytokine Expression in a Breast Cancer Mouse Model

Regular physical activity lowers or prevents the risk of heart disease, diabetes, some cancers, the development of hypertension, and death from these diseases through a reduction in inflammation. Cytokines, such as interleukin (IL)-6, IL-18, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) are major markers representing the inflammatory process. This study aimed to investigate cytokine mRNA expression levels of IL-6, IL-18, TNF-α, and CRP in hepatocytes from breast cancer xenograft mice with or without moderate exercise. Each of the 5 mice at SP Korea Company, Seoul, Korea in 2015 were randomly divided into 3 groups: control (CTL), breast cancer (BC), and breast cancer exercise (BCEX). The inflammatory markers were analyzed in 10-week-old female Balb/C nude mice hepatocytes (n = 15; CTL = 5, BC = 5, BCEX = 5). Moderate intensity physical activity in mice was performed on a treadmill at an intensity of 18 m/min for 12 weeks, at 30 min for 5 days per week. IL-6, IL-18, TNF-α, and CRP mRNA expression levels of the BCEX group were significantly decreased compared to those of the BC group (P < 0.05), with no difference to the CTL group. There might be a reduced inflammatory process via a reduction in TNF-α, IL-6, IL-18, and CRP expression in breast cancer mice that were subjected to moderate intensity exercise.

Analysis of the fatigue benefit, functionality, and body composition of a program of therapeutic exercise and healthy lifestyle habits in patients breast cancer operated.

e12533 Background: Numerous studies support the benefit of physical exercise in breast cancer, with a lower rate of fatigue, lower risk of recurrence and greater survival. In addition, it prevents cardiovascular diseases, diabetes and obesity. The objective of this work is to analyze the effect of a program of physical exercise and habits of healthy life on fatigue, functionality and body composition in breast cancer patients of the Medical Oncology Unit of the Hospital Virgen de la Victoria, Malaga. Methods: Prospective study on 97 patients with breast cancer after completing locoregional treatment and systemic chemotherapy. Treatment with hormone therapy and trastuzumab was allowed. All patients were without disease, without cardiovascular history that contraindicated the program and have signed the relevant informed consent. The duration of the program was 3 months and the parameter measurement was performed before and after. The main objective was analyze cancer-related fatigue and secondary functional parameters, anthropometric and adherence to Mediterranean diet. Fatigue, parameters functional and adherence to Mediterranean diet were evaluated by tests specific and anthropometric by different measurements including use of Tanita TBF-300A. Results: 97 patients were recruited, with a median age of 52 years (32 and 69), 60% had received neo/adjuvant chemotherapy, 84% hormonal therapy and 12% trastuzumab. Most patients underwent conservative surgery. (76%). After 3 months of intervention, women improved significantly cancer-related fatigue (p = 0.000), levels of diet adherence Mediterranean (p = 0.000), as well as functional parameters. One was observed statistically significant improvement in limb functionality/mobility upper, lower limb and general functionality (p = 0.005, p = 0.013 and 0.000, respectively). No differences were observed in terms of mass index body, fat mass or lean mass. Conclusions: This study shows the benefit in functionality and fatigue of an exercise program therapeutic and healthy lifestyle habits in breast cancer operated patients. Despite a significant increase in adherence to the Mediterranean diet, it is not they observed differences in anthropometric parameters.

The effect of longitudinal exercise programming in breast cancer patients.

TPS12124 Background: Obesity and weight gain are significant concerns for breast cancer survivors. Obesity at diagnosis is an established negative prognostic factor and studies suggest that post-diagnosis weight gain may increase risk for recurrence and decrease disease free survival. Various interventions such as dietary modification, physical activity, individualized counseling, cognitive behavioral therapy, and combinations of these interventions have been studied in order to identify strategies for weight loss in breast cancer survivors. However, one of the main challenges have been to show sustainability in these interventions. Given the adverse consequences of weight gain after diagnosis, continued efforts to identify appropriate weight management interventions aimed at promoting overall health and long term survivorship are needed. Methods: We have opened an investigator initiated Breast Cancer Exercise Study that provides a tailored exercise program and body health assessments for breast cancer patients along their treatment journey. We are enrolling women diagnosed with breast cancer up to 2 years after their diagnosis into a two 12-week exercise program. Participants’ biometrics and physical assessments will be assessed at baseline to determine the appropriate exercise intensity to implement. Women will attend private 1:1, 90min sessions, 3 days/week. At the end of the initial 12-week program, biometric assessments are again performed and participants are then randomized to either: a) continue with individual exercise classes, 2 days/week or b) continue with group exercise classes, 2 days/week. The study follows their long term outcomes including cancer recurrence, exercise adherence as well as quality of life symptoms. The functional health assessment and subsequent personalized exercise program utilizes kinesiology students from University of Hawaii-Manoa during their clinical practicum and is based at our community partner facility the Rehabilitation Hospital of the Pacific. Body assessments and other biomarkers are evaluated through expertise at University of Hawaii Cancer Center. Collectively, our study exemplifies our partnership with community facilities, utilizes cutting edge research and incorporates local students, to provide an important health program for cancer patients all the while enriching our understanding of the unique patient population. The results of this project may help to develop standardized exercise protocols for breast cancer survivors and provide insights to other important health concerns. Clinical trial information: NCT04013568 .

Protocol for the \u201cChemobrain in Motion \u2013 study\u201d (CIM \u2013 study): a randomized placebo-controlled trial of the impact of a high-intensity interval endurance training on cancer related cognitive impairments in women with breast cancer receiving first-line chemotherapy

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

Validation of an information-motivation-behavioral skills model of upper limb functional exercise adherence among Chinese postoperative patients with breast cancer.

The adherence to postoperative upper limb functional exercise in breast cancer (BC) patients is poor which can lead to adverse health outcomes. Effective intervention content to improve adherence is still unclear. The information-motivation-behavioral skills (IMB) model is a theoretical model that has been widely used to promote health behavior in many disease populations and may, therefore, help to explain and promote adherence to functional exercise. In this study, we validated the IMB model in a sample of postoperative BC patients. A cross-sectional study of 165 postoperative patients with BC was performed in a hospital. We collected information on demographics, functional exercise knowledge (information), personal and social motivation (motivation), objective skills and self-efficacy (behavioral skills), and functional exercise adherence (behavior). Measured variable path analyses were applied for the IMB framework. The IMB elements explained 37.9% of the variance in adherence. As predicted, behavioral skills had a direct effect on adherence (β = 0.509; P < 0.05) and mediated the effects of knowledge (indirect effect 0.092, P < 0.05) and motivation (indirect effect 0.251, P < 0.05) on adherence. Behavioral skills have a direct effect on functional exercise adherence and a mediating effect on the influence of knowledge and motivation on adherence. Thus, these factors represent key determinants of exercise adherence. The IMB model could be applied to the upper limb exercise adherence of postoperative BC patients. These findings indicate that the promotion of exercise adherence interventions may benefit from targeting patients' exercise adherence-related knowledge, motivation, and behavioral skills.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised...

Modulation of insulin-like growth factors following exercise in breast cancer: A meta-analysis of randomized controlled trials.

e22012 Background: Insulin resistance,Insulin-like growth factor 1 (IGF-1), IGF-2 and IGF binding protein-3 (IGFBP-3) are associated with breast cancer risk, cell growing, apoptosis and other tumor...

Abstract P5-15-08: Exercise intervention to run away from breast cancer treatment side effects: An integrative approach

Abstract Background. Some studies have shown that exercise increases breast cancer (BC) patients’ quality of life (QoL) during and after treatments. The aim of this study was to investigate the effect of an specific exercise intervention in QoL and in the exercise levels of these patients. Methods. A randomized controlled trial evaluated an intervention (IG) vs a control group (CG) in early stage BC patients who recently finished chemo &amp; radio therapies. Intervention consists on controlled group classes combining aerobic and resistance activities. CG maintained their previous lifestyle. QoL, leisure-time exercise levels (LTEL), chest (CMS) and legs maximal strength (LMS), physical capacity (PC) and some psychological variables, were assessed at baseline and after 3 months in both groups. Women who participated in the IG were followed up (FU) after 6 months. Statistical analysis (SA) were performed using unpaired t-test on continuous variables comparing CG vs IG, considering possible confounders. Pearson correlation analyses were employed to examine possible correlations. 6 months FU data were analyzed comparing baseline and after intervention results using non-parametric test (n=13). SA was performed with SPSS v18 software. 95% CI was calculated and statistical significance level of p &amp;lt; 0.05 was used. Results. 59 women (median 48.97±8.35 years old) completed this study. No differences between groups were observed at baseline. Average attendance rate to the program was 89%. There was a significant rise in LTEL (t123=16.33; p=0.0001) and in QoL (t123=2.88; p=0.005) comparing IG vs CG. Results also showed a correlation between QoL and LTEL in patients of IG only (r=0.22; p=0.013). Significant differences between groups were observed in both physical and psychological variablesafter training program. Table 1. Results summary comparing intervention and control group.VARIABLESIntervention Group (n= 27) Mean±SDControl Group (n=32) Mean±SDFollow-Up (n=13) Mean±SDQoL*+112.88±17.74±103.11±19.26110.96±14.40LTEL*+45.11±14.6114.87±4.7834.56±19.51Body Fat Mass34.63±6.736.47±7.4735.74±4.56Muscle mass41.3±3.1638.78±8.5141.48±2.01Strength Index*+2.6±0.832.12±0.692.32±0.58CMS*+45.89±11.0731.47±9.8753.76±12.42LMS*+93.07±27.369.00±24.94114.65±24.29PC*+32.58±4.9627.08±3.7332.11±7.10FACT-F *+135.94±18.20124.00±24.20138.24±17.49SF-36 Physical Dimension*+48.49±4.8345.61±5.8249.75±2.75SF-36 Psychological Dimension*+43.00±8.1137.03±12.5844.33±7.33Depression*+6.83±7.8312.55±10.775.88±5.19*Significant differences were found between control and intervention group. + Significant differences were maintained between baseline and follow-up assessments. No differences taking into account confounders were observed.Variable changes were maintained in FU participants assessed after 6 months. Correlation between QoL and LTEL (r=0.52; p=0.008) and significant weight loss (χ22=6.08; p=0.048) were observed. Conclusion. These results suggest that a specifically designed BC exercise program increases LTEL, which correlates to a better QoL. This may reduce psychological and physical side effects of systemic treatment in patients with early BC that have recently finished treatments, even producing lifestyle changes in BC patients that could be long lasting. Citation Format: Soraya Casla, Sara López-Tarruella, Yolanda Jerez, Iván Márquez-Rodas, Ricardo Cubedo, Isabel Calvo, Ana Martinez, Sara Cano, Rubén Barakat, Miguel Martín. Exercise intervention to run away from breast cancer treatment side effects: An integrative approach [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-08.

Modulation of Anthracycline-Induced Cardiotoxicity by Aerobic Exercise in Breast Cancer

Anthracycline-containing chemotherapy (eg, doxorubicin) is well known to cause dose-dependent, progressive cardiac damage clinically manifest as decreased left ventricular (LV) ejection fraction and, ultimately, heart failure (HF) (Table 1).1,2 Unfortunately, the only clinically accepted method to minimize injury is dose modification and/or therapy discontinuation.3 An important current challenge in breast cancer management is therefore to maximize the benefits of doxorubicin while minimizing cardiac damage. Identification and examination of new interventions to prevent and/or treat doxorubicin-induced cardiotoxicity are urgently required. View this table: Table 1. Stages of Doxorubicin-Induced Cardiotoxicity Aerobic exercise is a nonpharmacological therapy that promises to attenuate doxorubicin-induced cardiotoxicity. Aerobic exercise is well documented to improve systolic and diastolic function and attenuate pathological cardiac remodeling, resulting in improved exercise tolerance and resistance to fatigue during exertion in patients with HF.4,5 The cardioprotective properties of aerobic exercise in the context of doxorubicin have, in contrast, received scant attention. It is not generally used in cancer patients despite its lack of “side effects” and the paucity of alternative strategies to prevent/treat doxorubicin-associated cardiac damage. As a first step in the possible use of exercise in cancer patients, we reviewed the mechanisms of doxorubicin-induced cardiotoxicity and the available evidence supporting the utility of aerobic exercise to prevent/treat cardiac injury. We also explored the molecular mechanisms that may underlie the cardioprotective properties of aerobic exercise. These findings have implications for future research regarding the application and effectiveness of exercise and doxorubicin treatment in humans. The mechanisms underlying the antitumor function of anthracyclines have been described previously.6–8 Among the proposed mechanisms of cardiac injury, doxorubicin-induced generation of reactive oxygen species (ROS)9,10 is a central mediator of numerous direct and indirect cardiac adverse consequences (for review, see Minotti et al11). In the present report, we …

Benefits of exercise training on breast cancer progression and inflammation in C3(1)SV40Tag mice

Many observational epidemiologic studies suggest an association between exercise and breast cancer risk. However, the lack of controlled experimental studies that examine this relationship and the mechanisms involved weaken the basis for inferring a causal relationship. Inflammation plays a role in breast cancer progression and exercise has been reported to reduce inflammation; however, the anti-inflammatory effects of exercise in breast cancer have yet to be established. We examined the relationship between exercise training and systemic inflammation in relation to breast cancer progression in C3(1)SV40Tag mice. Female C3(1)SV40Tag mice were assigned to either exercise (Ex) or sedentary (Sed) treatment (n=12–14/group). Beginning at 4wks of age mice (Ex) were run on a treadmill for 60min/d (20m/min and 5% grade), 6d/wk for a period of 20wks. Mice were examined weekly for palpable tumors, and tumor number and volume were recorded. At 24wks of age mice were sacrificed and a more direct measure of tumor number and volume, and spleen weight was recorded. Plasma was analyzed for MCP-1 and IL-6 concentration using ELISA. Ex reduced palpable tumor number at sacrifice (24wks) by approximately 70% (P<0.05). Tumor volume was also reduced in Ex at 21–23wks (P<0.05). This reduction in tumor progression by Ex was associated with a reduction in plasma concentration of MCP-1 and IL-6, and spleen weight (P<0.05). These data provide strong support for a beneficial effect of exercise training on tumor progression in the C3(1)SV40Tag mouse model of breast cancer that may be partly mediated by its anti-inflammatory potential.

Abstract 5084: Treadmill exercise modulates AMP-activated protein kinase and downstream signaling in mammary gland of p53+/−, but not p53+/+ mice

Abstract Epidemiological data show that exercise is generally protective against breast cancer. Inhibition of mammalian target of rapamyocin (mTOR) through activation of AMP-activated protein kinase (AMPK) has been shown to be responsive to exercise. Decreased activation of ribosomal protein S6, a marker for mTOR inhibition, is associated with decreased growth and proliferation. Recently, this energy-sensing pathway has been shown to be inhibited by increased production of reactive oxygen species (ROS) leading to AMPK activation. ROS levels are maintained by p53-inducible anti-oxidant enzymes. Therefore, we hypothesized that energy sensing pathways that mediate the protective effects of exercise in breast cancer are modulated by p53 gene dosage. To test this hypothesis, we fed ovariectomized mice a high-fat diet (60% kcal) ad libitum for 10 weeks to model post-menopausal obesity. Mice were then randomized to a sedentary or exercise regimen (n=15/group). Exercised mice ran on a variable speed treadmill (5% incline, 20 m/min, 40 min/day, 5 days/week for 22 weeks). Changes in percent body fat were measured every 2 weeks using quantitative magnetic resonance. Immunoblot analysis was performed to measure phosphorylation of AMPK (Thr 172) and ribosomal protein S6 (Ser 240/244) relative to total levels in the mammary fat pad (MFP). Also, qRT-PCR was performed to measure mRNA expression of the p53-inducible anti-oxidant enzyme sestrin 1. At the end of the diet-induced obesity regimen, there was no effect of p53 genotype on percent body fat (54.4 ± 0.7 in p53+/+ versus 55.9 ± 1.1 in p53+/−). After 22 weeks of exercise, the EX mice displayed signficantly less percent body fat than sedentary controls, with no effect of genotype (44.4 ± 0.6 versus 47.8 ± 0.8 % respectively, p&amp;lt;0.05). Immunoblot analysis revealed that in p53+/− mice, but not p53+/+ mice, exercise increased AMPK phosphorylation. This increased AMPK phosphorylation was associated with decreased phosphorylation of ribosomal protein S6, a marker of mTOR pathway activation (n=3/group). The observed increase in AMPK phosphorylation in p53+/− exercised mice relative to sedentary p53+/− was associated with decreased mRNA levels of sestrin 1 (n=4-6/group), indicating that the p53+/− mice may have higher levels of ROS in the MFP. In conclusion, exercise may increase AMPK activation in MFP of p53+/− mice relative to sedentary p53+/− mice through an ROS-mediated mechanism. Current analysis is focused on understanding how exercise affects AMPK activation in the mammary fat pad of MMTV-Wnt-1 transgenic mice heterozygous for p53, and how this impacts mammary tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5084.

Lipid peroxidation and the protective effect of physical exercise on breast cancer

Physical exercise has been found to decrease the risk of breast cancer by undefined means. In our prior communication, we proposed lipid peroxidation to be a relevant mechanism for breast cancer protection associated with many established protective factors such as parity, oophorectomy, menopause, physical exercise, etc. [Gago-Dominguez M, Castelao J, Pike MC, Sevanian A, Haile RW. Role of lipid peroxidation in the epidemiology and prevention of breast cancer. Cancer Epidemiol Biomark Prevent 2005;14:2829-39]. In the present communication, we examine in detail the physical exercise-breast cancer relationship in light of the lipid peroxidation mechanism. We provide additional supporting evidence for the hypothesis that oxidative stress-induced apoptosis may be a mechanism responsible, at least in part, for the protective effect of exercise in breast cancer. Specifically, we describe (1) the sources of free radicals occurring during exercise, (2) existing experimental data on physical exercise, lipid peroxidation and cancer, (3) existing supporting data implicating exercise-induced reactive oxygen species (ROS) as the mechanism responsible for increased apoptosis in different cell systems, and (4) changes in the antioxidant enzymes glutathione S transferases (GSTs), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) that occur after physical exercise, which are believed to be a physiologic response to oxidative stress induced by physical exercise.