E Actinomycin IV biological activity therapy [33]. The substudy showed significant improvement in cognition after

E Actinomycin IV biological activity therapy [33]. The substudy showed significant improvement in cognition after cessation
E therapy [33]. The substudy showed significant improvement in cognition after cessation of therapy. The finding was consistent across all cognitive tasks and consistent in women taking either tamoxifen or letrozole at the 5-year time point. The observed effect size was moderate for the change in overall cognition. In this study, cognitive function was not assessed prior to the start of endocrine therapy, so it is not clear how cognition 1 year after cessation of therapy might have compared with baseline cognitive function prior to commencement of adjuvant endocrine therapy. Nevertheless, this study suggests that any effect that adjuvant endocrine therapy might have on cognition in postmenopausal women is at least partly reversible with cessation of endocrine therapy.Data from non-randomized comparisons ATACthat of those randomly assigned to tamoxifen or exemestane. After 1 year of use, exemestane was not statistically significantly associated with lower cognitive function in comparison with healthy controls, whereas 1 year of tamoxifen treatment was associated with worse performance in terms of verbal memory and executive function. The observed effect sizes were moderate for all affected cognitive domains. Three other non-randomized studies have examined the influence on cognitive function of tamoxifen compared with aromatase inhibitors [27,30,31]. Two studies found no statistically significant difference in overall cognitive function between patients taking tamoxifen versus aromatase inhibitors [30,31], but these studies were small and underpowered (Table 2). The third, a cross-sectional study of a small convenience sample of 31 postmenopausal women, suggested that learning and memory were worse in breast cancer patients treated for at least 3 months with anastrozole (n = 15) compared with tamoxifen (n = 16) [27]. However, the women who received tamoxifen in that study had been taking the endocrine therapy for significantly longer (mean of 23.8 months versus 14.3 months) and were significantly younger (mean of 48.2 years versus 57.4 years) than those who received anastrozole, and this may have confounded the results. Also, the cross-sectional design, with no pretreatment measures, makes it impossible to determine whether the results represent a change from pretreatment performance.In a pilot substudy of the randomized trial of Anastrozole, Tamoxifen Alone or Combined (ATAC) [26], the cognitive function of 94 breast cancer patients taking adjuvant tamoxifen or anastrozole (analyzed together) was compared with that of a convenience sample of 35 healthy untreated controls. None of the patients had had prior PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25636517 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 chemotherapy. Standard neuropsychological tests, which consisted of measures of processing speed, working memory, attention, visual memory, and verbal memory, were used. Women were tested after 12 to 60 months of adjuvant endocrine therapy (mean of 36 months). Those receiving adjuvant endocrine therapy performed less well on tests of verbal memory and processing speed compared with untreated controls. A comparison of the cognitive function of women taking anastrozole with that of women taking tamoxifen was not performed as the sample size was considered too small; thus, this study does not provide specific information on the impact of aromatase inhibitors on cognitive function.TEAMInterpretation and future research directions To date, the hypothesis that aromatase inhibitors might have an adverse impact on cognitive function and mi.