Abstract
Introduction: Fatigue and cognitive dysfunction commonly co-occur in breast cancer patients and survivors. However, the underlying neural mechanism is not clear. We performed a systematic review of studies that used neuroimaging methods to investigate structural and functional changes in the brain associated with fatigue in breast cancer patients and survivors.Methods: We searched PubMed, Scopus, EmBase, and Cochrane CENTRAL from January 2009 to May 2021 for studies that reported brain neuroimaging findings in relationship to fatigue in breast cancer patients or survivors. Neuroimaging methods included magnetic resonance imaging (MRI), positron emission tomography (PET), and electroencephalogram (EEG). We summarized structural and functional neuroimaging changes associated with fatigue.Results: Of the 176 articles retrieved, ten MRI studies reported neuroimaging findings in relationship to fatigue. Together these studies compared 385 breast cancer patients or survivors to 205 controls. Fatigue was associated with reduced white matter integrity and increased glutamate in the insula but changes in gray matter volume were not associated with fatigue score. Nine of the ten studies found significant associations between fatigue and functional changes in the frontoparietal cortex. In response to memory and planning tasks, fatigue was associated with increased activations in several regions of the frontoparietal cortex, however, overall performance on tasks was not reduced. Fatigue was also associated with extensive changes in the connectivity of brain networks that filter endogenous signals (salience network), internal attention (default mode network), and external attention (dorsal attention network). Subcortical regions associated with fatigue included insula (interoception), superior colliculus (sleep regulation), and thalamus (alertness). Functional brain changes before initiation of chemotherapy were a better predictor of post-treatment fatigue than chemotherapy itself.Conclusions: Fatigue in breast cancer is associated with widespread functional changes of brain regions and networks that affect executive function including memory, planning, internal and external attention. Observed changes likely represent a compensatory mechanism through which breast cancer patients and survivors try to maintain adequate executive function. Breast cancer patients scheduled to undergo chemotherapy are at high risk for developing fatigue even before the start of treatment.
Highlights
Fatigue and cognitive dysfunction commonly co-occur in breast cancer patients and survivors
One study that reported neuroimaging findings in breast cancer (BC) patients was removed because findings in relationship to fatigue were not reported (Vardy et al, 2019)
Cancerrelated fatigue (CRF) in BC patients and survivors is associated with few structural but extensive functional changes in cortical and subcortical regions and networks that process working memory, interoception, internal and external attention. Though it is unclear if the observed changes are the cause or the effect of CRF, they provide a neural basis for many of the cognitive symptoms and behaviors reported by BC patients and survivors with CRF including impaired memory, difficulty concentrating, hypervigilance of internal body signals, and reduced engagement with the external environment (AndersonHanley et al, 2003)
Summary
Fatigue and cognitive dysfunction commonly co-occur in breast cancer patients and survivors. Mental fatigue pertains to a variety of distressing cognitive symptoms including diminished concentration and attention, difficulty completing daily tasks, and perceived problems with short-term memory (Lin et al, 2009). This cluster of symptoms, which is often observed during chemotherapy, is colloquially referred to as “chemo brain” (Askren et al, 2014). Several studies have reported that patients with BC report fatigue and demonstrate worse cognitive performance on neuropsychological assessments even before the start of chemotherapy (Wefel and Schagen, 2012; Lange et al, 2014) These findings suggest that a central neurobiological mechanism likely contributes to CRF; the underlying neural mechanism is not known
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