Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study (original) (raw)
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Breast Cancer Research and Treatment, 2011
Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signedrank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment.
Journal of Cancer Survivorship, 2008
Introduction The selective estrogen receptor modulator, Tamoxifen (TAM), is one of the most frequently prescribed drugs for the treatment of breast cancer; however, its effects on the cognition of users have not been adequately studied. Although TAM is an effective anti-estrogen that blocks tumour growth in the breast, it could also influence the activity of other target estrogen sites, including the brain. The exact nature of this interaction is unknown. Methods A cross-sectional design was used to compare cognitive task performance of two treatment groups: 1) women using TAM for the treatment of early breast cancer (n=23); and 2) age-matched, healthy women not using TAM (n=23). All participants were pre-menopausal, and recipients of chemotherapy were excluded from the study. Results It was found that TAM users scored significantly worse than controls on tasks of immediate and delayed visual memory, verbal fluency, immediate verbal memory, visuo-spatial ability, and processing speed. Discussions/Conclusions Although limited by the lack of baseline data and pre-morbid intelligence measures, the results of this exploratory study suggest that at least in premenopausal women, TAM may exert a widespread negative influence on cognitive abilities. Implications for Cancer Survivors Larger, randomized, prospective trials are required to confirm these results; however, TAM use in pre-menopausal breast cancer may be associated with cognitive difficulties. Knowledge and understanding of these complications will be important for professionals in communicating both the benefits and risks of TAM use in breast cancer survivors.
2010
Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) versus tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores =0.28, p=0.04, 95% CI:0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.
The effects of hormone therapy on cognition in breast cancer
The Journal of Steroid Biochemistry and Molecular Biology, 2003
The use of hormonal therapies for the treatment of breast cancer is common, yet few studies have examined the possible cognitive effects. Several regions of the brain, important in memory and cognition, are rich in oestrogen receptors. As a result, the long-term use of anti-oestrogens may have potential consequences for cognition. This project aims to establish whether significant cognitive deficit exists in women receiving hormone therapy for breast cancer and to develop a cognitive package that is sensitive to the potential effects of oestrogen deficiency on cognition. Cognitive assessments measured a range of memory and attention functions in patient and control groups to identify whether cognitive impairment, if apparent, occurs at a widespread or function specific level. Ninety-four patients from the anastrozole, tamoxifen and combined (ATAC) trial and 35 non-cancer controls were assessed. Groups did not differ significantly in age or estimated full-scale intelligence. The patient group did not differ from controls on measures of working memory, attention and visual memory but was significantly impaired compared to the control group on measures of verbal memory (P = 0.026) and processing speed (P = 0.032). Cognitive performance in the patient group was not significantly related to length of time on trial or measures of psychological morbidity. As more and more hormonal agents are used in clinical trials of both adjuvant and preventive settings it is of vital importance that any potentially deleterious effects on cognitive function are measured adequately. Preliminary results from this study suggest that anti-oestrogen therapy may cause a specific deficit in verbal memory that corroborates the links between oestrogen levels and verbal memory often reported in studies of the cognitive benefits of hormone replacement therapy.
Cognitive changes associated with endocrine therapy for breast cancer
Maturitas, 2010
Endocrine therapy in the setting of breast cancer has undoubtedly advanced clinical outcomes in this disease, but treatment with endocrine therapy is accompanied by a wide spectrum of side effects. It is of prime importance to understand and characterize these toxicities to facilitate clinical decision-making. Somewhat surprisingly, there is a relative paucity of data pertaining to cognitive changes associated with endocrine therapy. In this article we review cognitive associated with two classes of endocrine therapy: (1) selective estrogen receptor modulators (SERMs; tamoxifen and raloxifene) and (2) aromatase inhibitors (AIs; anastrozole, letrozole, and exemestane). Companion studies to the Multiple Outcome of Raloxifene Evaluation (MORE), the Study of Tamoxifen and Raloxifene (STAR) and National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trials provide relevant data to understand the effect of SERMs on cognition. In contrast, substudies of the Arimidex, Tamoxifen Alone or in Combination (ATAC), Tamoxifen and Exemestane Adjuvant Multinational (TEAM) and Breast International Group (BIG) 1-98 trials juxtapose cognitive effects of AIs against those of tamoxifen. These and other studies are examined herein to provide a comprehensive overview of the effect of endocrine therapy on cognition.
British journal of cancer, 2012
In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function w...
Psycho-oncology, 2011
Objective: This study aimed to evaluate self-reported cognitive functioning of postmenopausal breast cancer patients before and during endocrine treatment compared with healthy female controls, and to investigate associations between self-reported cognitive functioning, cognitive test performance and anxiety/depression, fatigue, and menopausal complaints. Methods: Self-reported cognitive functioning, anxiety/depression, fatigue, menopausal complaints, and cognitive tests performance were assessed before (T1) and after 1 year (T2) of adjuvant endocrine treatment in postmenopausal chemotherapy-naı¨ve breast cancer patients. Self-reported cognitive functioning was assessed by the cognitive failures questionnaire and interview questions concerning cognitive complaints. Patients participated in the TEAM-trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive breast cancer. Identical information was obtained from healthy postmenopausal volunteers. Results: Two measures for self-reported cognitive functioning provided the distinctive results. At T1 and T2, healthy controls reported a higher frequency of cognitive failures than patients; change over time did not differ between groups. The prevalence of cognitive complaints did not differ between the groups at T1, but change over time regarding attention/concentration complaints differed between groups, due to an increased prevalence in tamoxifen users. Selfreported cognitive functioning showed moderate associations with anxiety/depression, fatigue, and menopausal complaints. Cognitive test performance was not associated with self-reported cognitive functioning, but weakly with anxiety/depression and fatigue. Conclusion: Adjuvant therapy with tamoxifen and exemestane did not influence the selfreported frequency of cognitive failures. Increased attention/concentration complaints were observed in tamoxifen users, but not in exemestane users. This latter finding should be confirmed with better validated instruments.
Journal of Clinical Oncology, 2010
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 ...
Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment
Psycho-oncology, 2009
Objective: Studies in breast cancer patients indicate that chemotherapy may cause subtle cognitive disturbances in some women, but the course is unclear. The current study evaluated the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients 1 year following completion of treatment.Patients and methods: Breast cancer patients scheduled to receive adjuvant chemotherapy (n=53) completed comprehensive neuropsychological testing before commencing chemotherapy (T1), 1 month after completing chemotherapy (T2), and again 1 year later (T3). A control group of women receiving adjuvant hormonal therapy (n=40) was tested at comparable intervals. A standardized regression-based approach was used to identify cognitive decline, and incidence of decline was compared across treatment groups.Results: Whereas at T2, chemotherapy patients were more likely to show cognitive decline than hormonal patients, by T3, the frequency of reliable cognitive decline was the same in both groups (11 and 10%, respectively). However, those chemotherapy patients receiving hormonal therapy at T3 were inferior to the chemotherapy patients not receiving hormonal treatment on composite measures of processing speed and verbal memory.Conclusion: These data suggest that there is a subtle negative impact of chemotherapy on cognitive function in breast cancer patients shortly following completion of treatment, but that this resolves within 1 year. However, given that our control group comprises breast cancer patients receiving hormonal therapy, and indications that hormonal therapy may also adversely affect cognition, such conclusions must be considered tentative. Copyright © 2008 John Wiley & Sons, Ltd.