DISCUSSION
Cancer, cognitive decline, early‐stage breast cancer, breast cancer
CANCER, BRAIN TUMOR, BREAST CANCER
We have demonstrated the feasibility, tolerability, and acceptability of memantine in patients with early‐stage breast cancer undergoing chemotherapy. While we did not demonstrate efficacy in this single‐arm trial, a high proportion of participants demonstrated stable or improved cognition, supporting future study of memantine in an adequately powered, controlled trial.There are limited data regarding the feasibility of pharmacological interventions for CRCI. However, in a trial of the stimulant methylphenidate administered during chemotherapy for breast cancer, researchers failed to reach target accrual.We are among the first to address a major research gap in interventions to prevent cognitive decline during chemotherapy. Specifically, most CRCI interventions have been tested years after completion of primary therapy. While there are many potential reasons for the lack of prevention studies, feasibility is likely among them. For example, a pilot study of the acetylcholinesterase inhibitor donepezil tested during radiation and chemotherapy in brain tumor patients closed prematurely.The safety and tolerability of medications for CRCI, especially when administered during active treatment, is a critical issue. For example, approximately 15 years ago, several small studies of erythropoietin demonstrated mixed effects for CRCI,In this early phase study with focus on feasibility, we have contextualized the observed cognitive changes in our cohort to those in observational studies reporting cognitive change during breast cancer chemotherapy. There are several major challenges in comparing data to prior studies, including that most have been small studies, with heterogeneity in measures used to quantify CRCI, and variable approaches to account for the fact that scores on repeated cognitive testing are inflated by enhanced familiarity with the test (i.e., practice effects). Given these issues, we compared the change in our primary outcome (DMS % correct at 12 s delay) to that in the observational study by Janelsins and colleagues–the largest in breast cancer (It is also important to acknowledge that many patients with breast cancer do not experience cognitive decline during chemotherapy. In this study, we focused on the proportion of who experienced clinically meaningful changes in cognition. While prevalence estimates of the proportion of patients who decline in objectively measured cognition varies between ~15% and 50%,In our study, we objectively evaluated cognitive change using a traditional, neuropsychological battery of measures recommended by the International Cognition and Cancer Task ForceWe also found promising early data as it relates to patient‐reported cognitive function. In Janelsins's cohort study, 45% of patients reported clinically significant decline.