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  • Review Article
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Cognitive effects of endocrine therapy for breast cancer: keep calm and carry on?

Nature Reviews Clinical Oncology volume 12, pages 597–606 (2015)Cite this article

Subjects

Key Points

  • Preclinical and clinical data indicate that endocrine treatment for breast cancer might have an adverse effect on cognition

  • Many studies exploring the influence of endocrine therapy on cognition are underpowered and have flawed designs, precluding any definite conclusions on the existence and clinical impact of such effects

  • Studies with a pretreatment neuropsychological assessment are essential to determine the potential cognitive effects of endocrine treatment and to identify patients who might be at risk of treatment-associated cognitive decline

  • Current guidelines permit the choice between different endocrine regimens in the treatment of breast cancer; thus, potential treatment-selective cognitive effects might influence treatment decision-making on an individualized basis

Abstract

The number of breast cancer survivors is gradually increasing and a subset of these patients experience long-term adverse effects of adjuvant systemic therapy, including cognitive decline. Surprisingly, relatively little is known about the long-term adverse effects of endocrine treatment on cognition. As 75% of all patients with breast cancer are eligible to receive hormonal treatment, understanding the potential neurocognitive adverse effects of such therapy is of utmost importance. Concerns about adverse cognitive effects of adjuvant endocrine therapy are timely, as recently updated guidelines recommend increasing the length of such therapy from 5 years to 10 years for a subset of patients. The decline of cognitive functions can have a detrimental impact on quality of life and might interfere with independent living. This Review discusses the tissue-selective side effects of endocrine therapies and specifically their impact on cognitive function, on the basis of clinical data; the neurobiological effects of endocrine therapies as observed in preclinical models are also discussed. We highlight the critical issues that need to be addressed in future preclinical and clinical studies in order to best assess the cognitive effects of endocrine treatment in patients with breast cancer.

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Figure 1: ER expression levels.
Figure 2: Endocrine therapies and tissue-selective effects.

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Acknowledgements

The authors thank Tesa Severson for critically reading the manuscript. The work of W.Z. is supported by an Alpe d'HuZes foundation/KWF Dutch Cancer Society Bas Mulder Award, A Sister's Hope and a Veni grant from The Netherlands Organization for Scientific Research (NWO). S.B.S. is supported by Dutch Cancer Society and Pink Ribbon grants, and S.C.L. by A Sister's Hope grant. S.C.L. is affiliated with the Department of Pathology, University Medical Center Utrecht.

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Authors and Affiliations

  1. Department of Molecular Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, Netherlands

    Wilbert Zwart & Sabine C. Linn

  2. Department of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, Netherlands

    Huub Terra & Sanne B. Schagen

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  1. Wilbert Zwart
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  2. Huub Terra
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H.T. researched the data under supervision of W.Z. and W.Z. and S.B.S. wrote the manuscript with input from H.T. and S.C.L.

Corresponding authors

Correspondence to Wilbert Zwart or Sanne B. Schagen.

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Overview of neuropsychological studies aimed to investigate the cognitive impact of endocrine therapies in breast cancer. (DOC 68 kb)

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Zwart, W., Terra, H., Linn, S. et al. Cognitive effects of endocrine therapy for breast cancer: keep calm and carry on?. Nat Rev Clin Oncol 12, 597–606 (2015). https://doi.org/10.1038/nrclinonc.2015.124

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