Enhancing cognitive function in breast cancer survivors through community-based aerobic exercise training

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Project Summary Women aged 50+ years comprise 77% of breast cancer diagnoses and 93% of all breast cancer survivors (BCS). Unfortunately, the interaction between cancer treatment and normal aging often results in a number of health sequelae. Up to 75% of BCS suffer cognitive changes during treatment, and over 45% experience clinically significant cognitive decline pre- to post-treatment. An optimum treatment for cancer-related cognitive impairment (CRCI) is likely one integrating interventions known to improve cognition in similar populations, such as older adults. Our previous research supports the efficacy of moderate-intensity aerobic exercise training for improving cognitive function in older adults without cancer. This work suggests that cardiorespiratory fitness (i.e., peak VO2) and brain structural and functional integrity (e.g., white matter microstructure, resting state functional connectivity) may underlie exercise-induced changes in cognitive function. We recently applied an aging framework to gain preliminary information on the effects of physical activity on cognitive function in BCS. Our work in this area suggests that aerobic exercise training may similarly ameliorate cognitive decline due to cancer and that cancer-related fatigue may also represent a mechanism of exercise’s cognitive benefits in the context of cancer. Our preliminary data in aging and cancer, along with the well-documented benefits of exercise relative to proposed CRCI mechanisms (e.g., cardiorespiratory fitness, fatigue), provide a compelling argument in support of aerobic exercise training for improving cognitive function in BCS. While evidence toward efficacy in this area is growing, few large trials have been conducted and none, to our knowledge, with consideration of dissemination and implementation a priori. We propose a clinical trial in which post-menopausal BCS (3-24 months post primary adjuvant therapy) will be randomized to a community-based aerobic exercise program or attentional control. This study utilizes a Hybrid Type I effectiveness-implementation design to investigate clinical effectiveness while gathering information on implementation success associated with our novel, community- based approach. Our exercise protocol is based upon our previous studies with demonstrated efficacy in older adults, and our community-based approach is based upon our previous studies with demonstrated implementation success in BCS and post-menopausal women without cancer. The specific aims are: 1) Examine the effectiveness of a 6-month, community-based aerobic exercise program, compared to control, on indicators of cognitive function (i.e., cognitive performance, neuroimaging metrics of brain health, self-reported cognitive impairment) in post-menopausal BCS; and 2) Gather information on the intervention’s potential for scalability as defined by the RE-AIM framework (i.e., reach, effectiveness, adoption, implementation, maintenance). We will also explore intervention interactions with clinical variables (e.g., moderators: chemotherapy treatment regimen, obesity status) and potential pathways by which aerobic exercise, compared to control, influences cognitive function (i.e., mediators: neuroimaging outcomes, cardiorespiratory fitness, fatigue).