title: Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II).
abstract: BACKGROUND
  Mild cognitive impairments have been recorded in cross-sectional studies of women with breast cancer receiving endocrine treatment. More comprehensive studies were warranted because aromatase inhibitors are being used increasingly in both chemoprevention and adjuvant settings. We report findings from the cognitive subprotocol of the International Breast Intervention Study (IBIS II), a double-blind placebo-controlled trial of anastrozole in postmenopausal women at high risk of developing breast cancer. We aimed to study and compare the effect of anastrozole versus placebo on memory and attention in these women.
  
  
  METHODS
  Between Jan 3, 2003, and Dec 21, 2005, participants were recruited into the cognitive subprotocol from five UK centres. Cognitive assessments were done before randomisation, at 6 months, and at 24 months. 227 of 249 women approached completed a comprehensive set of standardised cognitive tasks at baseline and were randomly assigned to receive anastrozole (1 mg/day for 5 years) or placebo. Psychological morbidity, endocrine symptoms, and self-reported cognitive complaints were also measured. The main outcomes were cognitive task scores at baseline, 6 months, and 24 months. Analyses were done by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31488319.
  
  
  RESULTS
  111 women were assigned to anastrozole and 116 women to placebo. At 6 months, ten women in each group were excluded from analysis, leaving a total of 207 of 227 (91%) women available for further assessments. At 24 months, 24 women were excluded from the anastrozole group and 32 from the placebo group, leaving 151 of 227 (67%) women. We did not note any significant differences between the groups for any of the cognitive tasks. By 6 months, 13 women in both groups reported changes to their memory and this had decreased to five women in the placebo group and three women in the anastrozole group by the 24-month assessment. Significantly more women in the anastrozole group complained of hot flushes at 24 months (23 of 76 [30%] vs 11 of 73 [15%], p=0.032, not corrected for multiple comparison), but this was the only difference in reported endocrine symptoms.
  
  
  CONCLUSIONS
  These findings show little or no impairment of cognitive performance with the use of anastrozole compared with placebo in postmenopausal women at high risk of developing breast cancer who were able to tolerate endocrine-related side-effects. Future studies assessing cognition should be done within randomised trials with baseline assessments to ascertain the true extent of the putative effects that treatments for breast cancer might have on memory and attention.
  
  
  BACKGROUND
  Cancer Research UK, London, UK (grant numbers C6280/A3162 and C6280/A6764).
authors.affiliation: Cancer Research UK Psychosocial Oncology Group, Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, UK.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Jenkins
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Ambroisine
authors.forename: Louise
authors.initials: L
authors.lastname: Atkins
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Fallowfield