Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial

Abstract

Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant (A) 5-years tamoxifen, (B) 5-years letrozole, (C) 2-years tamoxifen followed by 3-years letrozole, or (D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) vs. tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores=0.28, P=0.04, 95% CI: 0.02, 0.54, Cohen's D=0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen.

Fig 1

Treatment Schema for the BIG 1-98 trial Cognitive Function Substudy. Patients were assessed at the fifth year, toward the end of endocrine treatment and again at year 6, one year later. A total of 120 patients are included in the substudy analysis. [Color figure may be printed in grayscale.]

Fig 2

Estimated difference in means of the z-scores; negative values indicate cognitive function below age-adjusted norms. The p-values and 95% CIs of the treatment effects on tasks are based on the two-way ANOVA controlling for the effect of language. The percentages indicate the proportion of patients with “impaired” scores in the respective tasks (score >1.96 SD below the age-adjusted norm).

Fig 3

Estimated difference in means of the z-scores comparing letrozole vs. tamoxifen for the primary analysis population and monotherapy arms only (A), and comparing the monotherapy vs. sequential arms for the patients in the tamoxifen and letrozole groups (B). The p-values and 95% CIs of the treatment effects on tasks are based on the two-way ANOVA controlling for the effect of language.