Exercise Cardio-protection from Chemotherapy for Breast Cancer
Postdoctoral Research Fellow
University of Alberta
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One in nine women in Canada will be diagnosed with breast cancer during their lifetime, yet 88% will live for at least five years after diagnosis. Cardiovascular disease has become the most common cause of death of older breast cancer survivors, and breast cancer survivors are more likely to die of cardiovascular disease than women who have not had breast cancer. One of the contributing factors to the increased cardiovascular morbidity and mortality is anthracycline chemotherapy-related cardiotoxicity, or damage to the myocardium. The need for balance of oncological efficacy with cardiotoxicity of anthracycline chemotherapy has driven the active investigation of cardio-protective strategies. Exercise, an accessible and inexpensive intervention with numerous other health benefits, has demonstrated efficacy for attenuating cardiotoxicity in numerous preclinical (i.e. animal model) studies; a finding yet to be confirmed by clinical research. This dissertation investigated the potential for exercise cardio-protection from anthracycline chemotherapy in women diagnosed with breast cancer in three studies. The primary findings are: 1) during anthracycline treatment, adherence to supervised exercise training following the guidelines for cancer survivors varies widely; 2) the primary reason for withdrawal, missed exercise sessions, and non-adherence to prescribed intensity and/or duration was treatment-related symptoms; 3) despite low and variable adherence, women who enrolled in an exercise training program during anthracycline chemotherapy for breast cancer did not experience a clinically relevant deterioration of echocardiography-derived systolic global longitudinal strain or strain rate, which are both established predictive markers of cardiotoxicity; 4) global longitudinal strain has excellent intra-observer reliability and is consistently measurable in breast cancer patients, making it an excellent option for an outcome measure to assess cardio-protection; 5) performance of a single vigorous intensity aerobic exercise bout performed 24 hours prior to anthracycline treatment attenuates the acute NT-proBNP myocardial injury marker response to the first treatment, and alters hemodynamic regulation and cardiac structure after completion of treatment, but has no effect on longitudinal strain or strain rate or treatment symptoms. Overall this dissertation provides proof-of-principal for exercise cardio-protection, and contributes novel findings regarding exercise prescription and outcome measure assessment for future exercise cardio-protection studies during anthracycline treatment for breast cancer.
There is growing evidence that shift workers are at increased risk of cancer and a number of chronic diseases. As the prevalence of shift work is unlikely to decrease, an understanding of the factors that contribute to, and strategies that can be used to mitigate this risk are needed. Physical activity is known to improve health, and reduce chronic disease risk. However, evidence suggests that women shift workers may be less likely than other women to be sufficiently physically active. This dissertation aims to examine the effect that physical activity may have on improving health and reducing breast cancer risk in shift workers, by employing a variety of research methodologies. The first study is a systematic review of the literature on interventions aimed at improving the health of shift workers. This was conducted to understand what strategies have been most effective, as well as to identify gaps in the literature. The second study used cross- sectional data from the Canadian Health Measures Survey to understand patterns of physical activity and sedentary time in shift workers compared to day workers, as well as objective measures of physical fitness and obesity. The third and fourth studies aimed to understand women shift workers’ perspectives on physical activity, particularly barriers to and preferences for physical activity programming, using quantitative and qualitative research methods respectively. Findings from these four studies led to the development of a distance-based physical activity intervention, consisting of behavioural counselling sessions, and use of an activity tracker to encourage participants to meet Canada’s physical activity guidelines of 150 minutes per week of moderate-vigorous physical activity. This intervention was found to be feasible to implement in women shift workers, with preliminary evidence of efficacy. In summary, these studies highlight the important role that physical activity may play in improving health and reducing breast cancer risk in women shift workers. The intervention developed lays the groundwork for future randomized-controlled trials to determine the magnitude of the effect that regular physical activity may have on shift workers’ risk of breast cancer and other chronic diseases.
Taxane-based chemotherapy is frequently administered to treat breast cancer. However, side effects of taxanes include chemotherapy-induced peripheral neuropathy (CIPN) and cardiovascular complications, which negatively impact patient quality of life and long-term health. Exercise can significantly reduce cancer treatment side effects. However, information on exercise’s influence on taxane-specific side effects is limited. The primary aim of this dissertation was to evaluate the effect of exercise on taxane side effects, including CIPN and cardiovascular outcomes, in women with breast cancer. METHODS: Women with early-stage breast cancer were randomized to thrice-weekly exercise (EX) or usual care (UC) during taxane chemotherapy (4 cycles, 2-3 weeks apart). Patient-reported CIPN symptoms and quality of life (EORTC QLQ-C30 + CIPN20 subscale), clinical CIPN tests (vibration sensation and pinprick), patient-reported pain (Brief Pain Inventory) and cardiovascular outcomes, including heart rate and blood pressure at rest, and during and after submaximal exercise testing, were evaluated at baseline (pre-taxane chemotherapy) and end of chemotherapy. CIPN symptoms and quality of life were also evaluated at 0-3 days pre-chemotherapy cycle 4. RESULTS: Twenty-four women enrolled (EX: n=11, UC: n=13). Patient-reported CIPN symptoms were significantly worse by the end of chemotherapy in both groups for sensory (p
Background: Following chemotherapy, it is estimated that up to 95% of all cancer patients report cognitive changes such as complaints with memory and difficulty concentrating. This condition is referred to as chemotherapy-associated cognitive dysfunction or “chemo brain”. In addition, deficits in physical function are observed among those undergoing cancer treatment, as well as, long-term cancer survivors. While a decrease in physical activity participation has been shown among colorectal cancer patients over the course of chemotherapy, to date, changes in functional mobility over the course of chemotherapy has not been assessed in colon cancer patients using objective validated mobility tests. Furthermore, the association of cognitive and functional mobility dysfunction has not been explored. Purpose: To examine the effect of chemotherapy treatment on cognitive function, functional mobility and physical activity from baseline, to 6 months (end of chemotherapy) in individual being treated for colon cancer. Methods: At baseline and end of chemotherapy, participant completed a neuropsychological test battery, which included the Stroop, Hopkins Verbal Learning Test-Revised (HVLT-R), and Trail Making A & B (TMT A&B), a 6-minute walk test (6MWT), a measure of physical function, and a functional mobility testing battery, which included timed up and go (TUG) and gait speed. Demographic information and self-reported physical activity, using the International Physical Activity Questionnaire (IPAQ), were also collected at these time points. For the analysis of neuropsychological and mobility test scores, the paired t-test was used to test for the differences and assess the change in the mean scores from the baseline to 6-months. Results: No significant changes were noted in the HVLT-R, Stroop, and TMT-A and -B mean scores after completion of chemotherapy compared to baseline. Compared to baseline, no significant changes were observed for 6MWT, TUG, GS, or leisure-time physical activity after completion of chemotherapy. Conclusions: There were no significant changes in chemotherapy-associated cognitive, physical function, or functional mobility noted from baseline to the end of chemotherapy. In addition, physical activity levels and average time spent sitting did no change significantly. No definitive statements can be provided since the results are based on a small sample size.
INTRODUCTION: Physical activity (PA) levels in children who have completed treatment for acute lymphoblastic leukemia (ALL) have been shown to be lower than their healthy peers. Obesity and related health concerns have been recognized as long-term side-effect of cancer treatment. Motor performance and physical function have been shown to be lower in these children compared with children who have not had a cancer diagnosis. Whether or not these two physical factors are related to PA levels in these children is unknown. PURPOSE: To determine if motor performance and physical function are associated with PA in children who have completed treatment for ALL. METHODS: PA was measured using the Physical Activity Questionnaire for Older Children (PAQ-C); motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT-2 SF); and physical function was measured using the Six-Minute Walk Test (6MWT). RESULTS: Thirteen participants were recruited. PAQ-C scores were not related to standardized scores from the BOT-2 SF (Spearman’s rho, rs = 0.282, p = 0.35) and 6-minute walk distance (6MWD) (rs = -0.429, p = 0.14) and 6MWD Standard Deviation Score (SDS) (rs = -0.094, p = 0.76). Only 1/13 participants performed below average in the BOT-2 SF, and 11/13 participants walked shorter distances compared with published data from healthy children in the 6MWT (mean 6MWD SDS: -1.62). Body mass index SDS were significantly associated with measured 6MWD (rs = 0.602, p = 0.03) and 6MWD SDS (rs = -0.691 p = 0.01). CONCLUSION: PA was not associated with motor performance or physical function. Physical function was poorer compared with healthy children in 11/13 participants. Healthcare professionals can focus on improving physical function and improving weight management to help reduce risk of obesity and associated health consequences in children who have completed treatment for ALL. Future research should include a larger sample size and include psychosocial factors, such as self-efficacy and parental influence, in exploring factors related to PA childhood ALL survivors.
Fatigue is one of the most commonly reported side effects during treatment for breast cancer, andfor some individuals can continue for an extended period following treatment completion.Cancer-related fatigue is multi-factorial in nature, and one hypothesized mechanism of bothdevelopment and persistence of cancer-related fatigue following treatment is cardiorespiratoryand muscular deconditioning. The purpose of this study is to compare lactate threshold, VO₂peak and central vs. peripheral causes of muscular fatigue in breast cancer survivors withpersistent cancer-related fatigue (FG) and the control group (CG), breast cancer survivorswithout persistent cancer-related fatigue following treatment for breast cancer. METHODS:During first testing visit, power output at lactate threshold, lactate threshold as a percentageof peak power output, and absolute and relative VO₂ peak were determined using a gradedincremental maximal exercise test on a cycle ergometer. During the second testing visit centraland peripheral muscle fatigue following a sustained contraction of the right quadriceps wereassessed using the twitch interpolation technique and measurement of voluntary activation,control twitch, maximum voluntary contraction and endurance time. RESULTS: There were nosignificant differences in age, body weight, or time since completion of treatment betweengroups. There were no significant differences between groups in power output at lactatethreshold (FG 60.7±17.0 vs. CG 73.3±22.2 W, p=0.14), lactate threshold as a percentage of peakpower output (FG 46.8±8.6 vs. CG 55.0±14.7%, p=0.11), peak power output (FG132.12±38.2vs. CG 140.6±5.9 W, p=0.66), absolute VO2 peak (FG 1.51±0.39 vs. CG 1.74±0.38 L/min,p=0.19), or relative VO2 peak (FG 22.4±4.9 vs. CG 23.6±7.1 ml/kg/min, p=0.62). Results didapproach significance for power output at lactate threshold (p=0.10) and absolute VO₂ peak(p=0.08) when adjusted for age. Central fatigue was responsible for muscular fatigue in theivcontrol group, while muscular fatigue in the cancer-related fatigue group was more due toperipheral mechanisms. CONCLUSION: While no statistically significant differences werefound between groups, results suggest that deconditioning may play a role in cancer-relatedfatigue. Future research into the use of exercise training as a tool to improve deconditioning andthereby reduce this proposed aspect of cancer-related fatigue is warranted.