Effects of tamoxifen and exemestane on cognitive function in postmenopausal patients with breast cancer.

BACKGROUND: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast cancer patients. METHODS: Patients from the Tamoxifen and Exemestane Adjuvant Multinational trial received 5 years exemestane (exemestane group, n = 114) or 2.5 years tamoxifen followed by 2.5 years exemestane (sequential group, n = 92). Neuropsychological performance was assessed pre-endocrine therapy, after 1 year (ST follow-up) and at 5 years (LT follow-up). A control group of healthy participants (n = 120) were assessed with parallel intervals. With random effects modeling we evaluated cognitive changes from baseline to ST and LT follow-up. Statistical tests were 2-sided. RESULTS: After controlling for age, intelligence quotient, attrition, menopausal symptoms, anxiety and/or depression, and/or fatigue, the sequential group showed ST and LT decline compared with control participants on verbal memory (effect size [ES] = 0.26, P = .01; ES = 0.34, P = .003) and executive function (ES = 0.27, P = .007; ES = 0.38, P = .002). Compared with the exemestane group, the sequential group demonstrated ST decline on information processing speed (ES = 0.33, P = .01) and executive function (ES = 0.32, P = .01) and LT decline on verbal memory (ES = 0.33, P = .02). The exemestane group showed no cognitive decline compared with control participants. CONCLUSION: Cognitive adverse effects of tamoxifen alone and after switching to exemestane were observed, suggestive of a carryover effect of tamoxifen. Our results underline the need for well-controlled, prospective trials studying cognitive effects of endocrine therapy.

Relationships between educational achievement, intelligence, and perfectionism in adolescents with eating disorders.

OBJECTIVE: High performance at school is associated with the risk of eating disorders (EDs), and perfectionism is proposed as an explanatory factor for this association. This study aims to evaluate (a) potential discrepancies between the measured IQ of adolescents with EDs and the IQ that is expected given their educational track, and (b) to what extent perfectionism was associated with educational achievement independent from IQ. METHOD: WISC-III Verbal IQ, Performance IQ, and Full Scale IQ of 386 adolescent ED patients were compared with population norms for their educational track, using one-sample t tests. The association between self-oriented perfectionism (Eating Disorder Inventory-2) and educational achievement, adjusted for IQ, was determined with sequential ordinal regression analyses. RESULTS: Over 50% of the patients received pre-university education, the most complex educational track. For patients receiving education in the second most complex track, IQ-scores were lower than normative data for that track. For patients receiving pre-university education, the verbal IQ was lower than the norm for that track. Self-oriented perfectionism was associated with educational achievement independent from intelligence. DISCUSSION: This study suggests that high educational achievement is common in adolescents with EDs. Particularly for patients who receive education in the most complex tracks the demands at school may be higher than they can handle, based on their IQ. Self-oriented perfectionism contributed to educational achievement independent from IQ. Our results indicate that treatment for EDs should include awareness for the possibility of a too high target level of patients at school and perfectionism.

Intellectual functioning of adolescent and adult patients with eating disorders.

OBJECTIVE: Intelligence is a known vulnerability marker in various psychiatric disorders. In eating disorders (ED) intelligence has not been studied thoroughly. Small-scale studies indicate that intelligence levels might be above general population norms, but larger scale studies are lacking. The aim of this study was to determine intellectual functioning in ED patients and associations with severity of the disorder. METHODS: Wechsler's Full scale IQ (FSIQ), Verbal IQ (VIQ) and Performance IQ (PIQ) of 703 adolescent and adult ED patients were compared with population norms. Exploratory analyzes were performed on associations between IQ and both somatic severity (BMI and duration of the disorder) and psychological/behavioral severity (Eating Disorder Inventory [EDI-II] ratings) of the ED. RESULTS: Mean IQ's were significantly higher than population means and effect-sizes were small-to-medium (d = .28, .16 and .23 for VIQ, PIQ, and FSIQ). No linear associations between IQ and BMI were found, but the most severely underweight adult anorexia nervosa (AN) patients (BMI ≤ 15) had higher VIQ (107.7) than the other adult AN patients (VIQ 102.1). In adult AN patients PIQ was associated with psychological/behavioral severity of the ED. DISCUSSION: Our findings suggest that, in contrast with other severe mental disorders where low intelligence is a risk factor, higher than average intelligence might increase the vulnerability to develop an ED. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:481-489).

Cognitive functioning during long-term tamoxifen treatment in postmenopausal women with breast cancer.

OBJECTIVE: Endocrine therapy is widely used-often for many years-in women with breast cancer. Yet little is known about cognitive functioning after long-term use of tamoxifen. We examine cognitive sequelae, approximately 3 years after diagnosis, in postmenopausal women with breast cancer who were treated with adjuvant tamoxifen. METHODS: Data from participants who underwent surgical operation with or without radiotherapy, participants who received adjuvant tamoxifen, and healthy controls were collected. Neuropsychological tests were administered, and participants completed questionnaires on health-related quality of life (Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality-of-Life Questionnaire), menopausal symptoms (Functional Assessment of Cancer Therapy-Breast endocrine symptom subscale), and anxiety and depression (Hopkins Symptom Checklist). RESULTS: In total, 107 women participated (adjuvant tamoxifen group, n = 20; surgical operation/radiotherapy group, n = 43; healthy control group, n = 44). Women in the adjuvant tamoxifen group had received tamoxifen for a mean (SD) of 31.5 (18.6) months (range, 15-79 mo) and performed worse on verbal memory than the surgical operation/radiotherapy group (P < 0.05) and the healthy control group (P < 0.05). Participants in the adjuvant tamoxifen group performed worse on measures of fluency than healthy controls (P < 0.05). Furthermore, women in the adjuvant tamoxifen group reported worse cognitive functioning (P < 0.05) than women in the surgical operation/radiotherapy group or the healthy control group. CONCLUSIONS: Our results provide insights into cognitive functioning in women who receive long-term adjuvant tamoxifen treatment. By adding the surgical operation/radiotherapy group, we could control for the mental and physical influences of the diagnosis and treatment of breast cancer. Cognitive domains that rely on verbal abilities (verbal memory and fluency) seem to be at risk for deterioration after treatment with tamoxifen.

Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial.

PURPOSE: To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer (BC). PATIENTS AND METHODS: Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch postmenopausal patients with BC, who did not receive chemotherapy. Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC. RESULTS: Participants included 80 tamoxifen users (mean age, 68.7 years; range 51 to 84), 99 exemestane users (mean age, 68.3 years; range, 50 to 82), and 120 healthy controls (mean age, 66.2 years; range, 49 to 86). At T2, after adjustment for T1 performance, exemestane users did not perform statistically significantly worse than healthy controls on any cognitive domain. In contrast, tamoxifen users performed statistically significantly worse than healthy controls on verbal memory (P < .01; Cohen's d = .43) and executive functioning (P = .01; Cohen's d = .40), and statistically significantly worse than exemestane users on information processing speed (P = .02; Cohen's d = .36). With respect to visual memory, working memory, verbal fluency, reaction speed, and motor speed, no significant differences between the three groups were found. CONCLUSION: After 1 year of adjuvant therapy, tamoxifen use is associated with statistically significant lower functioning in verbal memory and executive functioning, whereas exemestane use is not associated with statistically significant lower cognitive functioning in postmenopausal patients with BC. Our results accentuate the need to include assessments of cognitive effects of adjuvant endocrine treatment in long-term safety studies.

The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

OBJECTIVE: Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment. METHODS: Two hundred and five postmenopausal breast cancer patients underwent a battery of neuropsychological tests before the start of endocrine therapy, 124 healthy subjects underwent the same tests. Proportions of cognitive impaired patients were calculated for each of four criteria for cognitive impairment, using (1) study-specific healthy controls and (2) published norms of healthy controls as reference groups. RESULTS: The prevalence of cognitive impairment varied greatly with the strictness of the criterion, as expected, but also was dependent on the reference group used. Cognitive impairment, relative to published norms, ranged from 1% for the strictest to 36.6% for the less strict criterion, cognitive impairment relative to study-specific healthy controls, ranged from 13.7 to 45.4% for the same criteria. CONCLUSION: This study highlights contrasting proportions of cognitive impairment by using different criteria for cognitive impairment and different reference groups. (Dis)advantages of the methods using a criterion for cognitive impairment, and of the use of published norms versus a study-specific reference group are discussed.

Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study.

BACKGROUND: Previous studies have indicated that a subset of cancer patients treated with chemotherapy show cognitive deficits and/or experience cognitive complaints, whereas literature about the influence of hormonal therapies on cognition is sparse. Because of the accumulating knowledge about the importance of estrogen for cognitive functioning, there is growing concern about adjuvant hormonal therapy for breast cancer (BC) affecting cognition. We examined the cognitive functioning of postmenopausal BC patients who were, following doxorubicin/cyclophosphamide (AC) chemotherapy, randomized to tamoxifen or exemestane, and compared their performance with that of non-cancer controls. MATERIALS AND METHODS: Thirty BC patients using tamoxifen and 50 patients using exemestane underwent interviews, questionnaires and cognitive tests, on average two years after completion of AC chemotherapy. Forty eight healthy controls were tested with similar measures. RESULTS: Memory complaints were reported by 28% of AC/tamoxifen users, 24% of AC/exemestane users and 6% of healthy controls (p=0.02). Cognitive testing revealed no statistically significant differences between tamoxifen and exemestane users, but suggested that tamoxifen use is possibly related to worse verbal functioning, while exemestane use is possibly related to slower manual motor speed. Both patient groups performed significantly worse than healthy controls on verbal fluency and information processing speed. DISCUSSION: Our findings show that sequential treatment of AC-chemotherapy and hormonal therapy in postmenopausal, primary BC is associated with lower test scores for certain cognitive functions, and provide indications for possibly distinctive associations for different types of hormonal treatment. Future research with larger groups is recommended to obtain a more definite picture.