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Observational Study
. 2022 Jul;194(1):113-126.
doi: 10.1007/s10549-022-06597-1. Epub 2022 Apr 27.

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

Brenna C McDonald #  1 , Kathleen Van Dyk #  2 , Rachael L Deardorff  3 , Jessica N Bailey  3 , Wanting Zhai  4 , Judith E Carroll  2 , James C Root  5 , Tim A Ahles  5 , Jeanne S Mandelblatt #  4 , Andrew J Saykin #  3
Affiliations
Observational Study

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

Brenna C McDonald et al. Breast Cancer Res Treat. 2022 Jul.

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.

Gov identifier: NCT03451383.

Keywords: Antiestrogen hormonal therapy; Breast cancer; Cognition; Multimodal MRI; Neuroimaging; Older women.

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Conflict of interest statement

Statements & Declarations

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

Figures

Fig. 1
Fig. 1
Voxel-based morphometry (VBM): Lower gray matter volume in older women with breast cancer treated with hormonal therapy relative to non-cancer controls at A) pre-treatment baseline and B) 12-month follow-up (Overall FWE-corrected p<0.05, Cluster-level puncorrected<0.05)
Fig. 2
Fig. 2
Voxel-based morphometry (VBM): Reduced gray matter volume from pre-treatment baseline to 12-month follow-up in A) Older women with breast cancer treated with hormonal therapy and B) Non-cancer controls (Overall FWE-corrected p<0.05, Cluster-level puncorrected<0.05)
Fig. 3
Fig. 3
Higher working memory-related functional MRI activation (2-Back>0-Back) in older women with breast cancer treated with hormonal therapy relative to non-cancer controls at 12-month follow-up (Overall p<0.001, Cluster-level puncorrected<0.05)
Fig. 4
Fig. 4
Increased working memory-related functional MRI activation (2-Back>0-Back) from pre-treatment baseline to 12-month follow-up in older women with breast cancer treated with hormonal therapy (Overall p<0.001, Cluster-level puncorrected<0.05)
See this image and copyright information in PMC

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