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Clinical Studies

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

British Journal of Cancer volume 132, pages 180–187 (2025)Cite this article

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Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

Highlights

  • Tamoxifen is associated with worse processing speed, verbal memory, executive function, and motor functioning.

  • The prevalence of cognitive impairment is twice as high in women taking tamoxifen than in controls without cancer.

  • Effects of tamoxifen and its metabolite endoxifen seem to be exposure dependent, especially in younger women.

  • Self-reported cognitive difficulties are associated with tamoxifen-related side effects, anxiety, depression, and fatigue.

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Fig. 1: Cognitive test performance.
Fig. 2: Tamoxifen exposure and cognitive function.

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Data availability

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

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Funding

The TOTAM-study was supported by an unrestricted MRACE grant (Erasmus MC, The Netherlands) [grant number 2017-108].

Author information

Author notes

  1. These authors contributed equally: Maryse J. Luijendijk, Sanne M. Buijs.

  2. These authors jointly supervised this work: Sanne B. Schagen, Ron H.J. Mathijssen.

Authors and Affiliations

  1. Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Maryse J. Luijendijk & Sanne B. Schagen

  2. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands

    Sanne M. Buijs, Agnes Jager, Stijn L. W. Koolen & Ron H. J. Mathijssen

  3. Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands

    Stijn L. W. Koolen

  4. Department of Medical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands

    Elsken van der Wall

  5. Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands

    Sanne B. Schagen

Authors
  1. Maryse J. Luijendijk
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  2. Sanne M. Buijs
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Contributions

ML, SB, AJ, SK, EW, SS and RM designed the research. ML, SB and RM acquired data. ML, SB and SS analysed the data. ML and SB wrote the manuscript. All authors revised the manuscript and approved the final version.

Corresponding author

Correspondence to Maryse J. Luijendijk.

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Competing interests

The authors declare no conflict of interest.

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee of the Erasmus Medical Center (MEC 2017-548) and was performed according the Declaration of Helsinki. All patients provided written informed consent.

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Luijendijk, M.J., Buijs, S.M., Jager, A. et al. Effects of tamoxifen on cognitive function in patients with primary breast cancer. Br J Cancer 132, 180–187 (2025). https://doi.org/10.1038/s41416-024-02914-1

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