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Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study

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Abstract

An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/− taxanes +/− endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/− taxanes +/− endocrine treatment (=BC + SYST; n = 26) compared to no systemic treatment (BC; n = 23) and no-cancer controls (NC; n = 30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/− endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/− endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC + SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.

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Acknowledgements

This study was funded by the Dutch Cancer Society (KWF 2009-4284). We thank Epie Boven, MD, PhD, Suzan van der Meij, MD, Vera Lustig, MD, and Monique Bos, MD, PhD, for their contributions to the patient recruitment. We are indebted to all patients and controls, as well as physicians and nurses of the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, VU University Medical Center, Flevoziekenhuis, Reinier de Graaf Gasthuis and Academic Medical Center, for providing patients for this study and the research assistants for helping collecting the data.

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Authors and Affiliations

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

    Sanne Menning, Michiel B. de Ruiter & Sanne B. Schagen

  2. Department of Radiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands

    Sanne Menning, Michiel B. de Ruiter & Liesbeth Reneman

  3. Department of Psychiatry, VU University Medical Center, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands

    Dick J. Veltman

  4. Department of Neuro-Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands

    Willem Boogerd

  5. Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands

    Hester S. A. Oldenburg

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  1. Sanne Menning
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  2. Michiel B. de Ruiter
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  7. Sanne B. Schagen
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Correspondence to Sanne B. Schagen.

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Funding

This study was funded by the Dutch Cancer Society (grant number KWF 2009–4284).

Conflict of interest

Author Menning declares that she has no conflict of interest. Author de Ruiter declares that he has no conflict of interest. Author Veltman declares that he has no conflict of interest. Author Boogerd declares that he has no conflict of interest. Author Oldenburg declares that she has no conflict of interest. Author Reneman declares that she has no conflict of interest. Author Schagen declares that she has no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Menning, S., de Ruiter, M.B., Veltman, D.J. et al. Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study. Brain Imaging and Behavior 12, 324–334 (2018). https://doi.org/10.1007/s11682-017-9695-x

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