Background: It is suspected that estrogen depletion resulting from treatment may contribute to cognitive compromise in patients with breast cancer. However, the evidence for estrogen effects on cognition is inconclusive, and the consequences of hormonal changes for cognitive function in patients with cancer rarely have been investigated. In this study, the authors investigated the effects of treatment-induced menopause and antiestrogen therapy with tamoxifen and aromatase inhibitors (AIs) on cognitive function.

Methods: Cognitive performance was assessed in 101 patients with breast cancer before the start of cancer therapy (T1), toward the end of neoadjuvant chemotherapy (T2), and 1 year after baseline (T3) using 12 cognitive tests. Menopause occurred in a subgroup of patients, and an overlapping subgroup started antiestrogen therapy with tamoxifen or AIs. Linear mixed-effects models that made it possible to determine effects at group levels and individual levels simultaneously were used for statistical analysis.

Results: At the group level, a significant favorable effect of induced menopause emerged in a test of executive function (P= .0035). Two additional group-level effects of induced menopause, both favorable, and 2 individual-level effects that were positive in some patients and negative in others were not significant when multiple testing was taken into account. No significant effects of tamoxifen or AIs on cognitive function were observed.

Conclusions: Hormonal changes did not appear to contribute to cognitive compromise in patients with breast cancer during the first year after diagnosis. Antiestrogen treatment with tamoxifen or AIs did not affect cognition, and the effects of induced menopause were more likely to be favorable. However, the possibility that some cognitive decline occurs in individual patients could not be excluded.