Intrinsic brain activity changes associated with adjuvant chemotherapy in older women with breast cancer: a pilot longitudinal study

Abstract

Purpose: Older cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer.

Methods: Chemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60-82 years) with stage I-III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity, were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed.

Results: In the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected = 0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected = 0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance.

Conclusions: Our study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer.

Fig. 1

Alterations in the amplitude of low-frequency fluctuation (ALFF) in the chemotherapy group from pre- (time point 1, TP1) to post-chemotherapy (time point 2, TP2). The highlighted area is a single cluster showing a statistically significant increase in ALFF from TP1 to TP2 (p-corrected < 0.05). This cluster includes parts of the right subcallosal gyrus (8, 16, −16), left subcallosal gyrus (−8, 14, −14) and right anterior cingulate gyrus (4, 22, −8; Brodmann 32). The color bar in the right lower panel indicates the scale of the t statistics for the within-group comparison of ALFF between the TP1 and TP2.

Fig. 2

Alteration of fractional amplitude of low-frequency fluctuation (fALFF) in the chemotherapy group from pre- (time point 1, TP1) to post-chemotherapy (time point 2, TP2). One cluster (indicated in yellow) in the left precuneus (0, −56, 44) shows a statistically significant decrease in fALFF from TP1 to TP2 (p-corrected < 0.05). The blue crosshair indicates the cluster peak (0, −56, 44) in each plane. The color bar in the right lower panel indicates the scale of the t statistics for the within-group comparison of fALFF between TP1 and TP2.

Fig. 3

Spearman correlation and the associated p-values between the changes in ALFF and changes in Pattern Comparison Processing Speed test scores from pre- to post-chemotherapy for the chemotherapy (CT) group (left) and the healthy control (HC) group (right). Linear regression was performed to obtain the fitting curve. Note: pat_compare_proc: Pattern Comparison Processing Speed