Project Summary/Abstract The long-term goal of this research is to reduce the functional impact of cognitive impairment and improve quality-of-life in women treated for breast cancer with cancer-related cognitive impairment (CRCI). The prevalence of CRCI following breast cancer is high and can persist chronically after treatment has ended. Breast cancer survivors often self-report cognitive deficits, primarily in executive functioning (planning, problem solving, multitasking), memory, and processing speed. These cognitive impairments can have substantial impacts on everyday life including work, community involvement, driving, and financial management. Neuroimaging studies suggest this may be due to altered activity in frontoparietal cognitive circuits. Metacognitive strategy training (MCST), in which participants are taught a general cognitive strategy that can be applied in known and novel contexts to devise task specific strategies to successfully engage in an activity, may provide a solution. Our overall research hypothesis is that MCST (1) will be feasible and (2) will improve behavioral indices of cognitive performance in women with CRCI which are associated with improved neural activation and functional connectivity in frontoparietal neural circuitry. This project aims to examine the feasibility of MCST and its impact in women treated for breast cancer on (1) cognitive performance, (2) frontoparietal resting-state functional connectivity, and (3) task-based BOLD activation and task-state functional connectivity in cognitive control circuitry. Participants (n=50) will be randomized to a MCST group (ten, 45-minute sessions over 10 weeks) or an inactive control group. Outcomes will be assessed at pre- and post-intervention. Feasibility outcomes will be analyzed using descriptive statistics reported with 95% confidence intervals. Treatment outcomes will be analyzed with an analysis of covariance (ANCOVA) to compare post-intervention outcomes between groups controlling for pre-test values. Cohen's d effect size with 95% confidence intervals will be reported. Neural outcomes will be examined as mediators of the treatment group effect on cognitive outcomes with a series of path analyses. Completion of this study is likely to result in a clinically feasible intervention to improve cognition and activity performance in individuals with CRCI that is prepared for efficacy testing. The proposed study is consistent with the research priorities of NCI's Division of Cancer Prevention, the Cancer MoonshotSM program, and PAR-22-216 which are to support research related to (1) chronic symptom management for improved quality of life and reduced cancer burden and (2) fostering greater collaboration between disciplines necessary to improve complex behavioral symptoms.

Project Narrative Breast cancer survivors self-report many cognitive deficits, primarily in executive function (planning, problem solving, multitasking), after cancer treatment (i.e. cancer-related cognitive impairments (CRCI). Despite the substantial impact of CRCI, rehabilitation for CRCI is minimal and knowledge to support intervention is lacking. This proposal evaluates if a novel metacognitive strategy training intervention, that targets engagement in activity, is feasible and can improve daily life cognitive performance with associated improvements in activation of neural circuitry underlying executive function.