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Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study

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Abstract

Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging (MRI) studies of breast cancer patients after cancer treatment. Here we report the first prospective MRI study of women undergoing treatment for breast cancer, with or without chemotherapy, as well as healthy controls. We hypothesized that chemotherapy-associated changes in gray matter density would be detectable 1 month after treatment, with partial recovery 1 year later. Participants included breast cancer patients treated with (CTx+, N = 17) or without (CTx−, N = 12) chemotherapy and matched healthy controls (N = 18). MRI scans were acquired at baseline (after surgery but before radiation, chemotherapy, and/or anti-estrogen treatment), 1 month after completion of chemotherapy (M1), and 1 year later (Y1). Voxel-based morphometry (VBM) was used to evaluate gray matter density differences between groups and over time. There were no between-group gray matter differences at baseline. Group-by-time interactions showed declines from baseline to M1 in both cancer groups relative to controls. Within-group analyses indicated that at M1 relative to baseline the CTx+ group had decreased gray matter density in bilateral frontal, temporal, and cerebellar regions and right thalamus. Recovery was seen at Y1 in some regions, although persistent decreases were also apparent. No significant within-group changes were found in the CTx− or control groups. Findings were not attributable to recency of cancer surgery, disease stage, psychiatric symptoms, psychotropic medication use, or hormonal treatment status. This study is the first to use a prospective, longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time. These gray matter alterations appear primarily related to the effects of chemotherapy, rather than solely reflecting host factors, the cancer disease process, or effects of other cancer treatments.

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Acknowledgments

The authors thank Charlotte Furstenberg, Leigh Chesnut, Susan Horrigan, Carrie Kruck, Vivian Horovitch-Kelley, and Drs. Peter Kaufman, Gary Schwartz, and Alexander Mamourian for their assistance. We are very grateful to our participants for their time and effort; this research would not have been possible without their willingness to participate during a challenging time in their lives. This study was supported by the National Cancer Institute at the National Institutes of Health (grant numbers R01 CA101318, R01 CA087845, and R25 CA117865) and the Indiana Economic Development Corporation (grant number 87884)

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The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Center for Neuroimaging, Department of Radiology and Imaging Sciences and the Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, 950 W. Walnut St., R2 E124, Indianapolis, IN, 46202, USA

    Brenna C. McDonald, Susan K. Conroy, John D. West & Andrew J. Saykin

  2. Department of Psychiatry and the Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH, USA

    Brenna C. McDonald, Tim A. Ahles & Andrew J. Saykin

  3. Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Tim A. Ahles

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  1. Brenna C. McDonald
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  2. Susan K. Conroy
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Correspondence to Brenna C. McDonald or Andrew J. Saykin.

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McDonald, B.C., Conroy, S.K., Ahles, T.A. et al. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 123, 819–828 (2010). https://doi.org/10.1007/s10549-010-1088-4

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