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

Abstract Abstract #1133 Background Adjuvant hormonal therapies (HT) are frequently used in primary breast cancer (BC), yet few studies have examined their potential impact on cognition. Fundamental and human research indicate that estrogens play an important role in certain cognitive functions; therefore it is plausible that HT can affect cognition in BC patients (pts). Due to different mechanisms of action, distinctive effects between selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) are possible. Methods Neuropsychological examinations were used to study cognitive performance before the start of adjuvant HT (T1) and after one year of HT (T2) in postmenopausal BC pts not qualified to receive chemotherapy. Study pts participated in the Dutch part of the international TEAM-trial, a prospective randomized study investigating tamoxifen (SERM) versus exemestane (AI) as adjuvant therapy for hormone-sensitive BC. The study sample consisted of 80 tamoxifen users (mean age 68.7 yrs, range 51-84) and 99 exemestane users (mean age 68.3 yrs, range 50-82). A healthy control group (n=120, mean age 66.2 yrs; range 49-86) was assessed with a similar interval. Differences in performance at T2 on 8 cognitive domains were studied among the three groups by use of ANCOVA twice: (1) adjusting for performance at T1 and (2) with additional adjustment for the covariates anxiety/depression, fatigue and menopausal symptoms at T2. Results After one year of therapy, exemestane users did not perform significantly worse than healthy controls on any cognitive domain. Tamoxifen users performed worse than healthy controls on 'verbal memory' (P=.003, Cohen's d = .43) and 'executive functioning' (P=.005, Cohen's d = .40) and worse than exemestane users on 'information processing speed' (P=.019, Cohen's d = .36). Adjustment for covariates did not change these results. For 'visual memory', 'working memory', 'verbal fluency', 'reaction speed' and 'motor speed' no significant differences between groups were found. Discussion After one year of therapy, tamoxifen has a negative impact on certain cognitive functions, while exemestane does not negatively affect cognition in this population. Although the burden of these effects on the daily life of pts has yet to be determined, intact cognition is known to be an important precondition for independent living and wellbeing. Currently, the options of HT in BC are increasing and optimization of HT with respect to the choice, sequence and duration of treatments is given high research priority. Our results underscore the need to include cognitive effects of HT in long-term safety studies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1133.