Abstract
Objective: We aimed to characterize local brain network connectivity in long-term breast cancer survivors compared to newly diagnosed patients.Methods: Functional magnetic resonance imaging (fMRI) and subjective cognitive and psychological function data were obtained from a group of 76 newly diagnosed, pre-treatment female patients with breast cancer (mean age 57 ± 7 years) and a separate group of 80, post-treatment, female breast cancer survivors (mean age 58 ± 8; mean time since treatment 44 ± 43 months). The network-based statistic (NBS) was used to compare connectivity of local brain edges between groups. Hubs were defined as nodes with connectivity indices one standard deviation or more above network mean and were further classified as provincial (higher intra-subnetwork connectivity) or connector (higher inter-subnetwork connectivity) using the participation coefficient. We determined the hub status of nodes encompassing significantly different edges and correlated the centralities of edges with behavioral measures.Results: The post-treatment group demonstrated significantly lower subjective cognitive function (W = 3,856, p = 0.004) but there were no group differences in psychological distress (W = 2,866, p = 0.627). NBS indicated significantly altered connectivity (p < 0.042, corrected) in the post-treatment group compared to the pre-treatment group largely in temporal, frontal-temporal and temporal-parietal areas. The majority of the regions projecting these connections (78%) met criteria for hub status and significantly less of these hubs were connectors in the post-treatment group (z = 1.85, p = 0.031). Subjective cognitive function and psychological distress were correlated with largely non-overlapping edges in the post-treatment group (p < 0.05).Conclusion: Widespread functional network alterations are evident in long-term survivors of breast cancer compared to newly diagnosed patients. We also demonstrated that there are both overlapping and unique brain network signatures for subjective cognitive function vs. psychological distress.
Highlights
Cancer and its treatments are associated with risk for cognitive dysfunction, most commonly in the domains of executive functioning, memory, attention, and processing speed [1, 2]
The POST-TX group demonstrated significantly greater executive dysfunction as measured by the Behavioral rating inventory of executive function adult (BRIEF-A) (W = 3,856, p = 0.004) but the groups did not differ in terms of Clinical assessment of depression (CAD) scores (W = 2,866, p = 0.627, Table 1)
The t statistics for these edges ranged from 3.11 to 4.22 (p < 0.042, family-wise error (FWE) corrected, Table 2)
Summary
Cancer and its treatments are associated with risk for cognitive dysfunction, most commonly in the domains of executive functioning, memory, attention, and processing speed [1, 2]. Neuroimaging studies suggest that cancer-related cognitive impairment (CRCI) results from injury to brain structure and function. Other groups have subsequently observed similar findings [10,11,12,13,14,15,16,17,18,19,20]. Most of these studies, including our own, have focused largely on global brain network characteristics and/or local connectivity among a limited number of discrete regions. Examination of all potential differences among local brain network connections is agnostic and requires larger samples but can provide a broader profile of potential biomarker features for modeling applications
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