Memory mayhem: Hormone therapy causing brain fog in patients with DCIS.

Abstract

575 Background: Long term hormonal therapy in ductal carcinoma in situ (DCIS) have been studied without consistent evidence to cause cognitive side effects. Here we evaluate the relation of using hormonal therapy (HT) in patients with DCIS with cognitive effects. Methods: TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients who had an ER positive DCIS. Two groups were made based on the receipt of hormone therapy (exemestane, tamoxifen, letrozole, anastrozole). Further, propensity score matching (PSM) was carried out to match age, sex, race, development of malignant neoplasm of breast, chemotherapy at any point. Outcomes of cognitive impairment were identified using ICD 10 CM codes R41.3, R41.0, F05, F02.81, and Alzheimer’s dementia was identified using ICD 10 CM code G30. Compare outcome analytic function was utilized to map the co-relation of HT with cognitive impairment. Results: 64,266 patients were identified with ER positive DCIS, of whom 63.18% (n=40,601) received HT. Patients who received HT were older (61.4 ± 12.3 vs. 61 ± 12.9, p<0.0001), and predominantly Caucasian (70% vs 65%, p<0.0001). On looking further into racial distribution of population, it was seen that Caucasians were predominant in both groups, followed by African Americans (12% vs. 11%, p=0.0016) and Unknown race (11% vs. 17%, p<0.0001), then Asians (4% vs. 4%, p=0.0675). Before PSM, it was seen that 7.55% (n= 2,818) patients had cognitive side effects compared to only 5.044% (n= 1,139) in group that did not receive HT (OR 1.537 (1.432,1.65), p<0.0001). Log-Rank Test for Kaplan-Meier curve was significant for the difference with hazard ratio 1.315, (1.227,1.409). A similar association was seen with Alzheimer’s dementia (0.735% vs. 0.547%, OR 1.346 (1.094,1.656), p= 0.0048) but Kaplan-Meier survival analysis did not show any significant difference between the groups. After PSM, both groups had 15,801 cases. The odds of developing cognitive impairment was higher in HT group (6.582% vs. 5.589%, OR 1.19, (1.082,1.309), p=0.0003). But Log-Rank Test for Kaplan-Meier curve did not show any significant difference (HR 1.047 (95% CI 0.954-1.149)). There was no significant difference for Alzheimer’s dementia development in either group (0.769% vs. 0.591%, 1.303 (0.994,1.709), p = 0.0548). Conclusions: Our study shows that HT significantly increases the odds of developing cognitive impairment. The limitation of the study is the duration of follow up. Usually, patients with DCIS live much longer and can have cognitive effects beyond the window of this study; hence a prospective long-term follow-up study is required to ascertain the relation of HT and cognitive side effects. Patients when starting the treatment should be counselled about the risk of developing cognitive side effects in future.