Background: Approximately 75% of women with BC have hormone receptor-positive (HR+) disease and are treated with anti-estrogen endocrine therapy (ET) in the adjuvant setting. Consistent with estrogens' well-established roles in neuroprotection and cognitive functioning, accumulating evidence suggests ET has adverse effects on cognition. However, there is a paucity of data regarding the cognitive effects of ET in older women, despite the fact that they are at greater risk of BC, HR+ disease, and cognitive impairment than their younger counterparts. Purpose: We conducted a prospective study to examine the cognitive effects of ET in older BC patients with a specific focus on verbal memory, the cognitive domain known to be most sensitive to the effects of estrogen deprivation. Methods: Forty-two chemotherapy-naïve non-demented HR+ BC patients aged 60+ underwent neuropsychological assessment before starting ET, and again after one year of treatment. This within-subjects design allowed us to control for pre-treatment effects of BC on cognition. The neuropsychological battery consisted of standardized measures assessing cognitive functioning across six domains: verbal memory, visual memory, processing speed, executive function, language function, and perceptual reasoning. Raw neuropsychological test scores were converted to age-adjusted z-scores to control for the effects of age on cognition. Change in mean-level performance from pre-treatment to post-treatment within each domain was examined using paired t-tests. Results: Participants exhibited significant decline from baseline pre-treatment performance in verbal memory over the year (t = 2.60, p = 0.01). This corresponds to a small to moderate effect size (d = 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). Conclusions & Implications: Our findings suggest specific adverse effects of ET on verbal memory, which is consistent with previous evidence that performance on verbal memory measures is highly sensitive to the effects of estrogen deprivation. This finding is of considerable clinical relevance given that multiple large-scale studies have found performance within this domain to be an early predictor of cognitive impairment and dementia. Moreover, that significant verbal memory decline occurred after just one year of treatment is particularly concerning given that patients are currently treated with these agents for at least five years, with extended treatment durations of up to 10 years becoming increasingly common. In light of the frequency with which ET is prescribed to older women, it is critical that the potential longer-term effects of ET on cognitive functioning are examined in future larger-scale studies. Our findings should be interpreted with caution because we did not include untreated HR+ BC controls, which are not feasible to recruit given current prescribing guidelines.

Citation Format: Emily A. Underwood, Kathleen I. Pritchard, Katarzyna Jerzak, Gerald Lebovic, Christine Elser, Paula Rochon, Mary C. Tierney. Cognitive sequelae of adjuvant endocrine therapy in older women treated for early-stage breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 601.