1. Conclusions- Discussion
Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal breast cancer patients: results from the Dutch TEAM trial
CMT Schilder1, C Seynaeve2, W Boogerd1, LVAM Beex3, CJH van de Velde4, JWR Nortier4, CM Gundy1, HM Huizenga5, SC Linn1, FSAM van Dam1, SB Schagen Netherlands Cancer Institute, Amsterdam; 2 Erasmus Medical Center, Rotterdam, 3 Radboud University Medical Center, Nijmegen, 4 Leiden University Medical Center, Leiden; 5 University of Amsterdam, Faculty of Psychology, Amsterdam, the Netherlands
Poster 1133
Introduction
Methods - continued
Cognitive tests
A comprehensive test battery, existing of 18 test indices, was designed to assess 8 cognitive domains (table 1):
Table 1
Results
Participant characteristics
Table 2
Results – continued
With respect to possible age differences on outcome:
In the group ≤65 years, tamoxifen users (n=30) performed significantly worse than healthy controls (n=60) on ‘executive functioning’ (P=.014, Cohens d=.54).
In the group >65 years:
- tamoxifen users (n= 50) performed worse than healthy controls (n=60) on ‘verbal memory’ (P=.003, Cohens d=.58) and ‘information processing speed’ (P=.03, Cohens d=.44).
- tamoxifen users performed worse than exemestane users (n=64) on ‘information processing speed’ (P=.005, Cohens d = .54).
Adjuvant endocrine therapy is widely prescribed for patients with hormone-sensitive breast cancer (BC) and contributes to an improved survival.
For postmenopausal BC patients, treatment with an aromatase inhibitor (AI) is an option as an upfront treatment or after treatment with tamoxifen, a selective estrogen receptor modulator (SERM).1
Given the evidence for relationships between estrogens and cognition provided by preclinical and neuropsychological studies2, effects of endocrine therapy on cognition are theoretically plausible.
Because mechanisms of action of SERMs and AIs are different, effects on cognition might also be different.2,3
We studied the effects of endocrine treatment on cognitive functioning in patients who participated in the Dutch part of the TEAM (Tamoxifen Exemestane Adjuvant Multicenter) trial, investigating 5 years of exemestane (AI) and 2.5 years of tamoxifen followed by 2.5 years of exemestane in post-menopausal, hormone sensitive BC.
*According to the Dutch version of the National Adult Reading Test
** Post-hoc tests: tamoxifen versus controls: P=.03; exemestane versus controls: P=.04;
tamoxifen versus exemestane: P=.71.
Cognitive test results (after 1 yr; adjusted for T1 scores/covariates):
No significant differences between Exemestane users and healthy controls on any cognitive domain (table 3).
Tamoxifen users performed worse than healthy controls on verbal memory (P=.006, Cohens d = .40) and executive functioning (P=.004, Cohens d = .41), and worse than exemestane users on information processing speed (P=.02, Cohens d = .36) (table 3).
No differences between groups with respect to visual memory, working memory, verbal fluency, reaction speed and motor speed.
Table 3
Conclusions- Discussion
Our results suggest that one year of adjuvant exemestane treatment is advantageous compared to one year of adjuvant tamoxifen treatment with respect to cognitive functioning in postmenopausal BC patients.
The analyses of the younger (≤65 years) and older (>65 years) women separately suggest that the cognitive effects of tamoxifen might be dependent on age.
More research is needed:
- to define the mechanism(s) of action of tamoxifen in the brain.
- to determine, for both tamoxifen and exemestane, the cognitive effects of a longer duration of treatment.
- to determine whether the absence of cognitive effects of exemestane is a specific property of exemestane, or a property of all AIs.
Objectives
To evaluate, prospectively, the effects of both tamoxifen and exemestane on cognitive functioning.
To compare the effects on cognitive functioning between tamoxifen and exemestane.
Statistical methods
Cognitive test scores at T1 and T2 were converted to standardized Z-scores based on the mean and standard deviation of the healthy control group.
The 8 outcome variables were expressed as the mean Z-score of tests that made up the particular cognitive domain (table 1).
Group comparisons of the 8 cognitive domains were made by ANCOVA’s: T2 scores were compared using T1 scores, anxiety/depression (Hopkins Symptom Checklist), fatigue (EORTC-QLQ-C30 fatigue scale) and menopausal symptoms (FACT-B ES) as covariates.
To investigate possible age differences with respect to the cognitive effects2, we repeated the ANCOVA procedure in two subgroups separately: (1) women aged ≤ 65 years and (2) women > 65 years.
Methods
Study population and procedure
Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in BC patients not receiving chemotherapy.
A healthy control group underwent the same assessments with a similar time interval of 1 year.
References
1. Buzdar AU, Coombes RC et al: Summary of aromatase inhibitor clinical trials in
postmenopausal women with early breast cancer. Cancer 112: , 2008
2. Sherwin BB, Henry JF: Brain aging modulates the neuroprotective effects of estrogen on
selective aspects of cognition in women: a critical review. Front Neuroendocrinol 29:88-113,
2008
3. Bender CM, Sereika SM et al: Memory impairments with adjuvant anastrozole versus
tamoxifen in women with early-stage breast cancer. Menopause 14: , 2007
4. Jenkins VA, Ambroisine LM et al: Effects of anastrozole on cognitive performance in
postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet
Oncol 9: , 2008
* Cognitive domain scores are expressed as Z-scores (see Statistical methods-section).
Values in this table represent the distance to the mean score of the healthy control group expressed in terms of SD’s (Mean Z-scores of the healthy control group are 0, SD’s are 1).
** P-value for ANCOVA of cognitive domain scores at T2, adjusted for cognitive domain scores at T1, anxiety/depression, fatigue and menopausal symptoms.
TAM = tamoxifen users, EXE = exemestane users, CON = healthy controls.
This original work was supported by an independent research grant from Pfizer