Effects of tamoxifen on cognitive function in patients with primary breast cancer

Tamoxifen may adversely affect cognitive function by interfering with estrogen action in the brain. Despite growing evidence for a relationship between tamoxifen and cognitive problems, findings remain inconclusive. While some tamoxifen-related side effects seem exposure-dependent with concentrations of tamoxifen or its main metabolite, endoxifen, this has never been investigated for cognitive function. We investigated cognitive function after two years of tamoxifen and its association with tamoxifen and endoxifen exposure.

135 women with breast cancer completed the Amsterdam Cognition Scan (ACS), an online neuropsychological test battery, after two years of tamoxifen. Test scores were converted to standardized Z-scores based on a matched 'no-cancer' control group. Tamoxifen and endoxifen concentrations and tamoxifen dose were regressed separately on cognitive functioning.

Patients reported mild cognitive complaints and had worse verbal learning, processing speed, executive functioning, and motor functioning compared to matched controls. After correcting for age, mean tamoxifen and endoxifen levels, as well as tamoxifen dose, were associated with worse performance on several cognitive domains.

Tamoxifen is adversely associated with objective as well as self-reported cognitive function, which may depend on the level of exposure to tamoxifen and endoxifen. Further research is warranted to confirm this hypothesis.