Functional dysconnectivity in breast cancer patients undergoing hormone therapy

INTRODUCTION: Breast cancer patients undergoing adjuvant hormone therapy commonly report adverse effects that can lead to lower quality of life and treatment nonadherence. How hormone therapy, independent of other systemic therapies, may impact patient functioning is a relatively new area of research with few neuroimaging studies delineating the effects. Prior nonspecific neuropsychological findings and the multifaceted role of estrogen in the brain suggest potentially diffuse effects of hormone therapy. The current study examined intrinsic neural functional organization and cognitive correlates unique to breast cancer patients undergoing hormone therapy. METHOD: Resting state functional magnetic resonance imaging was acquired from 24 breast cancer patients undergoing hormone therapy and 32 healthy controls. Resting-state functional connectivity (rsFC) was calculated between brain regions. Fractional amplitude of low frequency fluctuations (fALFF) was computed within a rsFC-derived mask to describe the regional properties within sites of dysconnectivity. Objective measures of cognition were obtained using neuropsychological tests and correlated with rsFC. RESULTS: Patients demonstrated extensive dysconnectivity relative to controls, largely characterized by parietal-occipital hypoconnectivity. Reduced rsFC occurred primarily between regions with increased fALFF. A modest relationship between rsFC and visual working memory was observed in breast cancer patients but not in controls. CONCLUSIONS: This study is the first to examine whole-brain rsFC in breast cancer patients undergoing hormone therapy. We found robust hypoconnectivity in patients, which demonstrated modest relationships with cognition. Identifying the pattern by which breast cancer and hormone therapy affect brain networks may aid in the development of therapeutic options for patients experiencing negative effects of hormone therapy, thus improving quality of life for cancer survivors. Further, the detection of abnormal brain function may help characterize treatment-associated neural changes that are not captured by standard cognitive measures.