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

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.

Fig. 1

Between-group interaction analyses of regional gray matter density declines in a chemotherapy-treated breast cancer patients relative to healthy controls from baseline to 1 month after chemotherapy; b breast cancer patients who did not receive chemotherapy relative to healthy controls over the same interval; and c chemotherapy-treated breast cancer patients relative to healthy controls from baseline to 1 year after chemotherapy (P_crit < .001, k = 1,400, see Table 3 for region descriptions)

Fig. 2

Regional gray matter density declines in chemotherapy-treated breast cancer patients from baseline to 1 month after chemotherapy (P_crit < .001, k = 1,400, see Table 3 for region descriptions)

Fig. 3

Regional gray matter density changes over time in chemotherapy-treated breast cancer patients. Decline was apparent in these regions from baseline to 1 month after chemotherapy with a recovery 1 year later or b persistent decline 1 year later (P_crit < .001, k = 1,400, see Table 3 for region descriptions)