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Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Cancer patients are concerned about treatment-related cognitive problems. We examined effects of antiestrogen hormonal therapy on brain imaging metrics in older women with breast cancer.

Methods

Women aged 60 + treated with hormonal therapy only and matched non-cancer controls (n = 29/group) completed MRI and objective and self-reported cognitive assessment at pre-treatment/enrollment and 12 months later. Gray matter was examined using voxel-based morphometry (VBM), FreeSurfer, and brain age calculations. Functional MRI (fMRI) assessed working memory-related activation. Analyses examined cross-sectional and longitudinal differences and tested associations between brain metrics, cognition, and days on hormonal therapy.

Results

The cancer group showed regional reductions over 12 months in frontal, temporal, and parietal gray matter on VBM, reduced FreeSurfer cortical thickness in prefrontal, parietal, and insular regions, and increased working memory-related fMRI activation in frontal, cingulate, and visual association cortex. Controls showed only reductions in fusiform gyrus on VBM and FreeSurfer temporal and parietal cortex thickness. Women with breast cancer showed higher estimated brain age and lower regional gray matter volume than controls at both time points. The cancer group showed a trend toward lower performance in attention, processing speed, and executive function at follow-up. There were no significant associations between brain imaging metrics and cognition or days on hormonal therapy.

Conclusion

Older women with breast cancer showed brain changes in the first year of hormonal therapy. Increased brain activation during working memory processing may be a sign of functional compensation for treatment-related structural changes. This hypothesis should be tested in larger samples over longer time periods.

ClinicalTrials.gov Identifier

NCT03451383.

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Data availability

The datasets generated and/or analyzed for the current study are not publicly available due to the ongoing nature of the study, but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors gratefully thank all the participants who graciously gave their time and effort to this work, and our research MRI technologists and neuroradiologist colleagues for their efforts to ensure the successful completion of the study. We also thank Michiel B. de Ruiter, PhD, for his assistance with brain age calculations and analysis. Finally, we wish to posthumously acknowledge the contributions of John D. West, MS to this research.

Funding

This research and the authors’ effort were supported by the National Institutes of Health, including National Cancer Institute Grants R35 CA197289, P30 CA008748, P30 CA082709, R01 CA129769, R01 CA244673, R01 CA172119, and K08 CA241337, and National Institute on Aging grants P30 AG010133, P30 AG072976, R01 AG068193, and R56 AG068086.

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Author notes

  1. Jeanne S. Mandelblatt and Andrew J. Saykin shared Co-senior authors.

  2. Brenna C. McDonald and Kathleen M. Van Dyk shared Co-first authors.

Authors and Affiliations

  1. Department of Radiology and Imaging Sciences, Indiana University School of Medicine and Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA

    Brenna C. McDonald, Rachael L. Deardorff, Jessica N. Bailey & Andrew J. Saykin

  2. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine and UCLA Jonnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA

    Kathleen Van Dyk & Judith E. Carroll

  3. Georgetown University and Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA

    Wanting Zhai & Jeanne S. Mandelblatt

  4. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    James C. Root & Tim A. Ahles

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  1. Brenna C. McDonald
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by BM, RD, JB, and WZ. The first draft of the manuscript was written by BM, KVD, and JM, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Brenna C. McDonald.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants under a protocol approved by the Indiana University Institutional Review Board (#1602851718, first approved July 27, 2016).

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McDonald, B.C., Van Dyk, K., Deardorff, R.L. et al. Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy. Breast Cancer Res Treat 194, 113–126 (2022). https://doi.org/10.1007/s10549-022-06597-1

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