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


Authors: McDonald, B. C.; Van Dyk, K.; Deardorff, R. L.; Bailey, J. N.; Zhai, W.; Carroll, J. E.; Root, J. C.; Ahles, T. A.; Mandelblatt, J. S.; Saykin, A. J.
Article Title: Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy
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. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: clinical article; controlled study; aged; neuroimaging; nuclear magnetic resonance imaging; follow up; magnetic resonance imaging; breast cancer; diagnostic imaging; breast neoplasms; physiology; cancer hormone therapy; brain; breast tumor; tamoxifen; cognition; aging; cross-sectional study; cross-sectional studies; letrozole; attention; functional magnetic resonance imaging; anastrozole; age determination; frontal cortex; cingulate gyrus; insula; working memory; older women; prefrontal cortex; voxel based morphometry; temporal cortex; procedures; selective estrogen receptor modulator; estrogen receptor modulators; memory, short-term; short term memory; visual cortex; executive function; humans; human; female; article; parietal cortex; cortical thickness (brain); fusiform gyrus; multimodal mri; processing speed; antiestrogen hormonal therapy; gray matter volume
Journal Title: Breast Cancer Research and Treatment
Volume: 194
Issue: 1
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2022-07-01
Start Page: 113
End Page: 126
Language: English
DOI: 10.1007/s10549-022-06597-1
PUBMED: 35476252
PROVIDER: scopus
PMCID: PMC9255382
DOI/URL:
Notes: Article -- Export Date: 1 July 2022 -- Source: Scopus
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  1. Tim A Ahles
    183 Ahles
  2. James Charles Root
    113 Root