PROJECT SUMMARY/ABSTRACT The goal of this project is to determine the efficacy of computerized cognitive training for breast cancer survivors (BCS) suffering from cancer-related cognitive impairment (CRCI). For millions of cancer survivors, CRCI is a prevalent, severe, and persistent problem that negatively impacts work outcomes (work ability and productivity), health perception, and health-related quality of life. Evidence suggests that up to 75% of the more than 3.8 million BCS in the U.S. will experience cognitive changes that may persist for years after treatment ends. Unfortunately, the scientific basis for managing these cognitive changes in cancer survivors is extremely limited. Available evidence from pilot studies, including our own work, suggests that computerized cognitive training, which is based on the principles of neuroplasticity (ability of brain neurons to re-organize and form new neural networks), may be a viable treatment option. However, previous trials to date have been limited by lack of attention-controlled designs, small samples, and limited follow-up. Therefore, to overcome limitations of past studies and build on our pilot results, the purpose of this 2-group, double-masked, randomized controlled trial is to conduct the first full-scale efficacy trial to compare computerized cognitive training (BrainHQ) to computerized active attention control (Sudoku, crossword, word find, etc.) in BCS. Specific aims are to: (1) test the efficacy of computerized cognitive training on improving perceived cognitive function immediately post- intervention and over time, compared to active attention control; (2) test the efficacy of computerized cognitive training on cognitive performance over time compared to attention control; and (3) explore transfer effects on real-world, everyday outcomes including work-related outcomes and health-related quality of life over time compared to active attention control. This proposal has been peer-reviewed and endorsed by the NRG Oncology Research Base of the NCI Community Oncology Research Program (NCI NCORP) and the NCI Division of Cancer Prevention has approved NRG Oncology to conduct the trial at their affiliated sites. A total of 386 eligible BCS will be identified and consented through the NCI NCORP and NCI National Clinical Trials Network (NCTN) sites, composed of over 2,000 participating locations including community and minority clinical oncology sites. Outcomes will be collected at four time points: baseline, prior to intervention (T1), immediately post-intervention (T2), 3 months (T3), and 6 months (T4) post-intervention. Data will be analyzed using linear mixed models for repeated measures. The current proposal responds directly to the NCI Notice of Special Interest to test interventions designed to address the adverse aging-related effects of cancer and cancer treatments, builds on our previous pilot studies while also making methodological improvements, and leverages access to all NCORP sites. Therefore, this will be the first full-scale study to test computerized cognitive training in cancer survivors with CRCI and provide empirical evidence for clinicians’ recommendations and survivors’ treatment selections for managing cognitive impairment.

PROJECT NARRATIVE This double-masked randomized controlled trial will leverage the NCI National Community Oncology Research Program (NCI NCORP) and NCI National Clinical Trials Network (NCTN) sites to conduct the first national, full- scale test of a computerized cognitive training program (BrainHQ) against a computerized active attention control program to improve self-reported (perceived) and objective (performance) cognitive functioning as well as examine its impact on other real-world, everyday outcomes in breast cancer survivors with cancer and cancer treatment-related cognitive impairment. Positive or negative findings about this easily accessible therapeutic treatment option will help provide evidence to guide clinicians’ recommendations and survivors’ treatment selections for managing this prevalent, persistent, disruptive, and often debilitating problem.