Abstract PO2-19-01: A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition?
Authors: Kumar Prashanth Ashok , McDowell Erinn , Bubb Amy , Huang Danning , Sperry Susan , Benjamin Sam , Sivapiragasam Abirami 
Published: May 2024

Abstract
Background: Estrogen (ER) and Progesterone (PR) receptors are rich in regions of the brain involved in cognitive functions, like the hippocampus and cerebral cortex. Animal models have shown that estradiol regulates neurocognition and plays an important role in the normal brain development. Hormone positive (HR+) breast cancers (BC) comprise 70% of the disease and the standard of care in the post-menopausal group is the use of Aromatase Inhibitors (AI) for at least 5 years. While “chemo brain” is a well-recognized term, neurocognitive changes from estrogen inhibition by AI have not been clearly defined. As neurocognition is multi-faceted, information on specific aspects affected by AI use is unclear. We hope to answer this through our trial. Design: The study is a single arm, self-controlled prospective observational cohort study in which, post-menopausal BC patients who are to be started on AIs will undergo a battery of neurocognitive tests just before starting AI, at 6 months and at 12 months after being on AI. The changes at 6 and 12 months will be compared to baseline. The tests will involve objective [Hopkins verbal learning test revised (HVLT), Controlled Oral Word Association Test from Multilingual Aphasia Examination, Trial Making Test A and B, and Recall and Recognition of Word List encoded from the HVLT] and subjective/patient-reported [The Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog)] components. Tests for anxiety [Generalized Anxiety Disorder (GAD)–7], depression [Patient Health Questionnaire (PHQ)-9] and working memory (Working Memory Tasks from the Wechsler Adult Intelligence Scale) will also be assessed. While the objective tests involve providing patients with specific instructions and asking them to complete the tasks, the FACT Cog questionnaire uses a self-reported 37-item questionnaire enabling assessment of their perceived symptoms. The tests have been summarized in the table. Eligibility criteria: ER/PR+ post-menopausal BC and DCIS patients who are English speaking and are planning to start AIs will be included. Patients who have received hormonal therapy or chemotherapy in the past, those who are scheduled to receive chemotherapy, those who have undergone Whole brain Radiation therapy (RT), those with a premenopausal status, and those having comorbid conditions that could affect cognitive functioning (like any form of dementia or brain metastasis) will be excluded. Specific aims: Our aim is to see if there are progressive neurocognitive changes compared to an age-appropriate baseline and to see if changes to both objective and perceived cognitive changes occur over the course of AI use, in post-menopausal HR+ BC patients. Statistical methods: The T-test and McNemer test will be used. The normal values provided from the test may be used as a standard to justify normal or abnormal values from the collected data. Therefore, a percentage of normal (or abnormal) subjects in each time point can be derived and compared using the McNemar's test. Present accrual and target accrual: 4 patients have been accrued as of June 2023 with a target accrual of 80 patients [80% power to detect a significant change, at a p of 0.05]. Contact information for people with a specific interest in the trial: Dr Abirami Sivapiragasam (abisiva2019@yahoo.com), Dr Sam Benjamin (benjamis@upstate.edu), Dr Prashanth Ashok Kumar (ashokkup@upstate.edu), Amy Bubb (bubbam@upstate.edu).
Summary of the neurocognitive tests employed in the trial.
Citation Format: Prashanth Ashok Kumar, Erinn McDowell, Amy Bubb, Danning Huang, Susan Sperry, Sam Benjamin, Abirami Sivapiragasam. A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-01.