The cognitive effects of endocrine therapy in survivors of breast cancer: A prospective longitudinal study up to 6 years after treatment

Abstract

BACKGROUND: After treatment of primary breast cancer, endocrine therapy (ET) is prescribed for patients with hormone receptor-positive cancers. Despite ET recommendations of 5 to 10 years of treatment, to the authors' knowledge there is little prospective study of its impact on cognitive function over an extended period of time. ET has known pharmacologic effects on the brain. Cognitive side effects are a concern for many women, with mixed findings reported in various studies. The current prospective longitudinal study examined the neuropsychological effects of ET over time, up to 6 years after treatment. METHODS: A total of 189 survivors of early-stage breast cancer enrolled in the study prior to initiating ET if prescribed, and were followed at 6 months (175 patients), 12 months (173 patients), and for 3 to 6 years (102 patients) with self-report and neuropsychological assessments. Using linear mixed models, the authors examined whether neuropsychological performance or impairment rates differed over time based on whether or not ET was received. RESULTS: The authors did not find any effect of ET on neuropsychological performance or impairment at any time point among survivors who received it compared with women who did not. However, those who participated in the 3-year to 6-year year visit demonstrated better executive function at baseline. CONCLUSIONS: In the current observational cohort study, no detrimental effect of ET on cognitive function was identified in survivors of early-stage breast cancer receiving treatment with ET compared with those who were not. Cancer 2019;125:681-689.

Cognitive Functioning and Psychological Well-being in Breast Cancer Patients on Endocrine Therapy

“…There are mixed data on the cognitive effects of ET (Table IV). In the recently published prospective longitudinal Mind Body Study, Van Dyk et al (17) reported on the complex long-term effects of ET on neuropsychological functions (17). The analysis was based on both neuropsychological testing and self-reported data in 189 BC patients among which follow-up was extended to 3-6 years in 102 participants.…”

“…Across most domains, there was similar improvement in both groups during the years of follow-up. The significance of these results is justified by the large number of patients, long follow-up in more than half of the cases, complex methodology in various domains and careful statistical analysis; the design of the follow-up lowered practice effects (17). Nevertheless, the confounder effects of chemotherapy (about half of the patients in both groups received chemotherapy <3 months within entering the study), varying ET and menopausal status were not excluded.…”

“…Some studies included control groups of healthy individuals (5,13,14,15,24). BC patients non-treated with ET (5,12,14,15,17,40) or both of healthy controls and untreated BC patients (5,14,15). The study of healthy controls may compensate for physiological timely decline of cognitive functioning.…”

“…Another issue is study retention, i.e. the proportion and composition of cases having dropped out (11,17). Attrition may result in the selection of data and miss the most vulnerable cases; this phenomenon is more relevant in studies with long follow-up.…”

“…Similar consequences of endocrine therapy (ET) have been less intensively investigated. Some data suggest that these longterm therapies cause significant cognitive deficits as compared to surgery-only or healthy control cases (5,(12)(13)(14), while other studies show only minor (15,16) or no such effects (17). Since endocrine therapy varies according to age and risk status, it is even more difficult to distinquish between the effects of the various treatment regimens including tamoxifen or the aromatase inhibitors with or without GnRH analogs (15,18,19).…”