Abstract Background: Whether treatment with aromatase inhibitors (AI) may be associated with the development of cognitive or other mental impairments is under debate. Few studies have carefully assessed AI-associated changes in cognitive function, and none have assessed differences between the three third-generation AIs – anastrozole, letrozole, and exemestane. We initiated a prospective clinical trial to compare baseline and 1-year change in neurophysiological testing in women initiating adjuvant AI.Patients and Methods: Women with a hormone receptor-positive stage 0-III breast cancer who were about to begin AI treatment were eligible for enrollment. We compared intra-individual neurophysiological testing results at baseline (Session I) and following one year of AI (Session II). Cognitive/behavioral assessment included standardized tests sensitive to 8 neuropsychological domains: General Intelligence, Attention, Perceptual-motor Performance, Working Memory, Visual Long-term Memory, Verbal Long-term Memory, Language, and Executive Functioning. Scoring was based upon age- and education-adjusted normative data. In addition, participants completed several subjective reports of cognitive, physical, and emotional functioning.Results: To date, 53 subjects enrolled in Session I, and 30 completed Session II. Analysis of the 30 women who completed both sessions revealed statistically significant differences (with the significance level set at p=0.05, test-wise), including: impairment from Session I to Session II on the PASAT Trial I (p=0.005) and improvement from Session I to Session II on the following tests: FAS Total (p<0.001); Animal Naming (p=0.025); RAVLT I-V, B, Delay, and Immediate (p<0.001 for all); RAVLT 5-1 (p=0.017); RAVLT % (p=0.022); Logical Memory I (p=0.005) and II (p<0.001); WMS-Faces I & II (p<0.001 for both); WAIS-Picture Completion (p=0.027); and WAIS-Vocabulary (p<0.001).Discussion: Only a few studies have examined the effect of AI treatment on cognitive functioning. Findings from the present study suggest that, following the administration of AI for 1 year, women as a group appear to exhibit impairments in attention (as evidenced by PASAT performance) and possibly in executive functioning. However, there was also improved performance in the areas of language, verbal long-term memory, and visual long-term memory. These preliminary results suggest a need to be sensitive to the possibility that AI treatment may have mixed effects on cognitive and related behavioral functions. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4084.
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