Amy A. Kirkham

Feasibility of a Lifestyle Intervention on Body Weight and Serum Biomarkers in Breast Cancer Survivors with Overweight and Obesity

Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre-post test design, conducted from November 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle intervention modeled on the Diabetes Prevention Program in early stage breast cancer survivors (N=14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were completed at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were postmenopausal women aged 54.6±8.3 years with obesity (body mass index 30.1±3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8±5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8±1.2 kg at 36 weeks. In exploratory analysis, participants who lost >7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Prevention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs.

Exercise Prevention of Cardiovascular Disease in Breast Cancer Survivors

Thanks to increasingly effective treatment, breast cancer mortality rates have significantly declined over the past few decades. Following the increase in life expectancy of women diagnosed with breast cancer, it has been recognized that these women are at an elevated risk for cardiovascular disease due in part to the cardiotoxic side effects of treatment. This paper reviews evidence for the role of exercise in prevention of cardiovascular toxicity associated with chemotherapy used in breast cancer, and in modifying cardiovascular risk factors in breast cancer survivors. There is growing evidence indicating that the primary mechanism for this protective effect appears to be improved antioxidant capacity in the heart and vasculature and subsequent reduction of treatment-related oxidative stress in these structures. Further clinical research is needed to determine whether exercise is a feasible and effective nonpharmacological treatment to reduce cardiovascular morbidity and mortality in breast cancer survivors, to identify the cancer therapies for which it is effective, and to determine the optimal exercise dose. Safe and noninvasive measures that are sensitive to changes in cardiovascular function are required to answer these questions in patient populations. Cardiac strain, endothelial function, and cardiac biomarkers are suggested outcome measures for clinical research in this field.

Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review

QUESTION What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data? DESIGN Systematic review with meta-analysis. PARTICIPANTS Women diagnosed with breast cancer who were before, during or after treatment. OUTCOME MEASURES Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12-minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test. RESULTS Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment. CONCLUSION Aerobic capacity and upper extremity strength in women diagnosed with breast cancer are generally lower than population norms. Assessment of values for lower extremity strength is less conclusive. As more research is published, expected values for sub-groups by age, treatment, and co-morbidities should be developed. [Neil-Sztramko SE, Kirkham AA, Hung SH, Niksirat N, Nishikawa K Campbell KL (2014) Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review.Journal of Physiotherapy60: 189-200].

Lateral trunk lean gait modification increases the energy cost of treadmill walking in those with knee osteoarthritis.

OBJECTIVE To compare the energy expenditure of increased lateral trunk lean walking - a suggested method of reducing medial compartment knee joint load - compared to normal walking in a population of older adults with medial knee osteoarthritis (OA). METHOD Participants completed two randomly-presented treadmill walking conditions: 15 min of normal walking or walking with ten degrees of peak lateral trunk lean. Lateral trunk lean angle was displayed in front of the participant in real-time during treadmill conditions. Energy expenditure (VO2 and METs), heart rate (HR), peak lateral trunk lean angle, knee pain and perceived exertion were measured and differences between conditions were compared using paired t-tests. RESULTS Twelve participants (five males, mean (standard deviation (SD)) age 64.1 (9.4) years, body mass index (BMI) 28.3 (4.9) kg/m²) participated. All measures were significantly elevated in the lateral trunk lean condition (P < 0.008), except for knee pain (P = 0.22). Oxygen consumption (VO2) was, on average 9.5% (95% CI 4.2-14.7%) higher, and HR was on average 5.3 beats per minute (95% CI 1.7-9.0 bpm) higher during increased lateral trunk lean walking. CONCLUSION Increased lateral trunk lean walking on a treadmill resulted in significantly higher levels of steady-state energy expenditure, HR, and perceived exertion, but no difference in knee pain. While increased lateral trunk lean has been shown to reduce biomechanical measures of joint loading relevant to OA progression, it should be prescribed with caution given the potential increase in energy expenditure experienced when it is employed.

Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors

Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof‐of‐concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors.

The utility of cardiac stress testing for detection of cardiovascular disease in breast cancer survivors: a systematic review.

Background Heart function tests performed with myocardial stress, or “cardiac stress tests”, may be beneficial for detection of cardiovascular disease. Women who have been diagnosed with breast cancer are more likely to develop cardiovascular diseases than the general population, in part due to the direct toxic effects of cancer treatment on the cardiovascular system. The aim of this review was to determine the utility of cardiac stress tests for the detection of cardiovascular disease after cardiotoxic breast cancer treatment. Design Systematic review. Methods Medline and Embase were searched for studies utilizing heart function tests in breast cancer survivors. Studies utilizing a cardiac stress test and a heart function test performed at rest were included to determine whether stress provided added benefit to identifying cardiac abnormalities that were undetected at rest within each study. Results Fourteen studies were identified. Overall, there was a benefit to utilizing stress tests over tests at rest in identifying evidence of cardiovascular disease in five studies, a possible benefit in five studies, and no benefit in four studies. The most common type of stress test was myocardial perfusion imaging, where reversible perfusion defects were detected under stress in individuals who had no defects at rest, in five of seven studies of long-term follow-up. Two studies demonstrated the benefit of stress echocardiography over resting echocardiography for detecting left ventricular dysfunction in anthracycline-treated breast cancer survivors. There was no benefit of stress cardiac magnetic resonance imaging in one study. Two studies showed a potential benefit of stress electrocardiography, whereas three others did not. Conclusion The use of cardiac stress with myocardial perfusion imaging and echocardiography may provide added benefit to tests performed at rest for detection of cardiovascular disease in breast cancer survivors, and merits further research.

Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT

BACKGROUND Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. METHODS Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. RESULTS Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (p<0.01) decreased, and ejection fraction (p=0.02) and systolic strain rate (p<0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p<0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. CONCLUSION The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.

Utility of Equations to Estimate Peak Oxygen Uptake and Work Rate From a 6-Minute Walk Test in Patients With COPD in a Clinical Setting.

PURPOSE: To determine the utility of equations that use the 6-minute walk test (6MWT) results to estimate peak oxygen uptake ( o2) and peak work rate with chronic obstructive pulmonary disease (COPD) patients in a clinical setting. METHODS: This study included a systematic review to identify published equations estimating peak o2 and peak work rate in watts in COPD patients and a retrospective chart review of data from a hospital-based pulmonary rehabilitation program. The following variables were abstracted from the records of 42 consecutively enrolled COPD patients: measured peak o2 and peak work rate achieved during a cycle ergometer cardiopulmonary exercise test, 6MWT distance, age, sex, weight, height, forced expiratory volume in 1 second, forced vital capacity, and lung diffusion capacity. Estimated peak o2 and peak work rate were estimated from 6MWT distance using published equations. The error associated with using estimated peak o2 or peak work to prescribe aerobic exercise intensities of 60% and 80% was calculated. RESULTS: Eleven equations from 6 studies were identified. Agreement between estimated and measured values was poor to moderate (intraclass correlation coefficients = 0.11-0.63). The error associated with using estimated peak o2 or peak work rate to prescribe exercise intensities of 60% and 80% of measured values ranged from mean differences of 12 to 35 and 16 to 47 percentage points, respectively. CONCLUSIONS: There is poor to moderate agreement between measured peak o2 and peak work rate and estimations from equations that use 6MWT distance, and the use of the estimated values for prescription of aerobic exercise intensity would result in large error. Equations estimating peak o2 and peak work rate are of low utility for prescribing exercise intensity in pulmonary rehabilitation programs.

Comparison of aerobic exercise intensity prescription methods in breast cancer.

INTRODUCTION Exercise plays an important role in cancer rehabilitation, but a precise prescription of exercise intensity is required to maximize the benefits of this intervention. It is unknown whether different methods of prescribing aerobic exercise intensity achieve the same intensity. Breast cancer treatments may alter exercise response and thereby may affect the accuracy of these methods. PURPOSE The purpose of this study was to compare the accuracy and achieved intensity of four common methods of prescribing exercise intensity within and between breast cancer patients recently finished chemotherapy (n = 10), survivors finished treatment (n = 10), and healthy controls (n = 10). METHODS The methods compared were as follows: the American College of Sports Medicines metabolic equation for treadmill walking (METW), heart rate reserve (HRR), direct heart rate (DIRECT HR), and RPE. The methods were used to prescribe 60% oxygen consumption reserve (VO2R) in four randomly assigned 10-min periods of treadmill walking with expired gas collection to evaluate 1) achieved intensity (measured % VO2R) and 2) accuracy (defined as: [60% VO2R-achieved intensity]). RESULTS The accuracy of the methods was not equivalent across groups (P = 0.04). HRR and METW did not differ across groups and were most accurate in patients. HRR, METW, and DIRECT HR were all more accurate than RPE in survivors (P ≤ 0.01). RPE was the least accurate in all groups. The accuracy of DIRECT HR was much lower in patients than that in survivors and controls (P ≤ 0.01). CONCLUSIONS The four methods of exercise intensity prescription varied in accuracy in prescribing 60% VO2R and did not achieve equivalent exercise intensities within breast cancer patients, survivors, and healthy controls. HRR and METW were the most accurate methods for exercise intensity prescription in breast cancer patients and survivors.