Exemestane Shows Scant Effect on Cognition


SAN ANTONIO — Adjuvant exemestane appears to have little effect on cognitive function in postmenopausal women with breast cancer, but women on adjuvant tamoxifen perform significantly worse than do healthy controls in several cognitive domains after 1 year of treatment, based on results of a substudy of the TEAM (Tamoxifen Exemestane Adjuvant Multicenter) trial.

After 1 year, researchers found that there were no significant differences in cognition between women who received adjuvant exemestane (Aromasin) and healthy controls after adjustment for baseline neurocognitive test scores and other covariates.

However, those women who received adjuvant tamoxifen performed significantly worse on verbal memory and executive functioning than did healthy controls. In addition, the tamoxifen groups also performed worse than exemestane users on information processing speed, Dr. Christina M. Schilder reported in a poster presentation at the San Antonio Breast Cancer Symposium.

“Our results suggest that 1 year of adjuvant exemestane treatment is advantageous, compared with 1 year of adjuvant tamoxifen treatment with respect to cognitive functioning in postmenopausal breast cancer patients,” wrote Dr. Schilder, of the Netherlands Cancer Institute in Amsterdam, and her colleagues.

Investigators in the TEAM trial compared the efficacy of 5 years of exemestane with 2.5 years of tamoxifen followed by 2.5 years of exemstane in postmenopausal women who had hormone-sensitive breast cancer. This subanalysis included Dutch patients involved in the study–80 women who were on tamoxifen and 99 who were on exemestane. They were compared with 120 healthy controls.

The study patients underwent neuropsychologic assessments at baseline and again after 1 year of adjuvant endocrine therapy. A healthy control group underwent the same assessments with a similar time interval.

The comprehensive test battery consisted of 18 test indices that were designed to assess eight cognitive domains including verbal, visual, and working memory; information processing speed; executive functioning; verbal fluency; and reaction speed.

Cognitive test scores at baseline and at 1 year were converted to standardized z scores, based on the mean and standard deviation of the healthy control group. The analyses were adjusted for anxiety, depression, fatigue, and menopausal symptoms.

Among women who were aged 65 years and younger, 30 tamoxifen users performed significantly worse on executive functioning than did 60 healthy controls.

Among women who were older than 65 years, 50 tamoxifen users performed worse on verbal memory and information processing than did than 60 healthy controls. Also in this age group, tamoxifen users performed worse on information processing speed than did exemestane users.

Further research is needed to determine cognitive effects of the drugs over a longer period of time and to establish whether exemestane's lack of an effect on cognition is a specific property of exemestane or whether it is a result of all aromatase inhibitors, the investigators noted.

Dr. Schilder reported that she has received grant support from Pfizer Inc., which manufactures Aromasin. The TEAM study is funded by Pfizer.

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