Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

Introduction: Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Methods: Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Results: Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p=.046) and cognitive functioning (p<.02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p<.05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p=.03). This hyper-correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p=.005). Conclusions: Our findings could not be accounted for by psychological distress and suggest that non-CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.