Investigating the effect of exercise on brain health in breast cancer patients

The aim of this study is to conduct a pilot study that investigates the effects of a supervised 8-week multimodal exercise intervention on cerebrovascular and cognitive function in female breast cancer patients. This will be determined objectively by assessing the following outcomes: (1) Cerebrovascular function, determined by measuring the cerebrovascular responsiveness (CVR) to both physiological (hypercapnia; 5% carbon dioxide) and psychological stimuli (cognitive battery) (2) Cognitive function, determined by a battery of individual cognitive tasks that are summated to reflect total cognitive capacity. Study design and ethical considerations An 8-week quasi-randomised, controlled-trial of female breast cancer patients (n=24) who will be assigned to either a multimodal exercise intervention or waitlist group (control) will be conducted collaboratively at the University of Southern Queensland (USQ) Toowoomba, The Fit Lab Toowoomba, and Queensland X-ray Toowoomba. Participants will visit USQ, The Fit Lab and Queensland X-ray prior to the commencement of the study, to establish baseline measurements. Participants will undergo anthropometric (body weight, height, hip, and waist circumference), functional capacity (60s sit-to-stand, 400m walk) and strength testing measurements under the supervision of an Accredited Exercise Physiologist at The Fit Lab. Dual-energy X-ray absorptiometry will be used to determine body composition measurements (lean and fat mass, bone mineral content and density) of the participants at Queensland X-Ray by an accredited technician. Participants will undergo cerebrovascular, cognitive, and cardiovascular measurements at USQ. Cognition will be measured via an iPad using the Trail Making Task Parts A and B, Spatial Span Test and the National Institute of Health (NIH) Toolbox. . Cerebrovascular measurements will be measured non-invasively using transcranial Doppler ultrasonography (TCD). These measurements include CVR to physiological (hypercapnia; 5% carbon dioxide) and cognitive stimuli. Hypercapnia will require participants to breath a gas containing 5% carbon dioxide and 21% oxygen in a balance of nitrogen gas for 3 minutes following breathing room air for 1 minute prior, via a two-way non-rebreathing valve whilst wearing a nose-clip. The CVR to cognitive stimuli will be assessed during individual cognitive tasks and summated to achieve a total composite CVR to cognitive stimuli. Finger photoplethysmography (human non-invasive blood pressure and haemodynamic monitor) will be used to measure cardiovascular function, with heart rate and arterial blood pressure being measured on a continuous beat-to-beat basis. Participants will complete a validated nutritional questionnaire to estimate energy intake over a typical 24 h period to ensure any changes observed in the primary outcomes are primarily due to the effects of exercise and not changes in nutritional behaviour. Additionally, participants will complete the Profile of Mood States (POMS) questionnaire to calculate total mood disturbance. All measurements, as well as the Yale Physical Activity Survey (YPAS) and POMS, will be repeated 1 week following the completion of the study at a similar time of day to their baseline measurements. Exercise intervention Participants allocated to the exercise group will participate in a supervised multimodal exercise program for up to three sessions per week for 8 weeks. The exercise intervention is an established program delivered externally by Accredited Exercise Physiologists at The Fit Lab. It has been adapted from previous research that has validated the safety of exercise interventions in patients with breast cancer (Cormie et al. 2013; Casla et al. 2015). Each session will comprise aerobic exercise and muscle strength training (i.e. multimodal exercise training) and last for approximately 60 min, including a 5 min warm-up and 5 min cool down. Aerobic exercise training will involve, for example, rowing, walking on a treadmill and riding a stationary bike. Examples of muscle strength exercises include chest press, lat pulldown and leg press. These would be expected to be performed at a moderate to vigorous intensity. The exercise session swill be conduction in person in groups of no more than 12 people. The exercise sessions will be self-paced, with progressive overload techniques put in place to ensure exercise capacity and muscle strength progression. An attendance sheet will be used to determine participant compliance to the intervention.