Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation

• Published in: Breast cancer research and treatment 2014-09, Vol.147 (2), p.445-455
• Main Authors: Askren, Mary K., Jung, Misook, Berman, Marc G., Zhang, Min, Therrien, Barbara, Peltier, Scott, Ossher, Lynn, Hayes, Daniel F., Reuter-Lorenz, Patricia A., Cimprich, Bernadine
• Format: Article
• Language: English
• Subjects: Biomarkers; Biomarkers - metabolism; Brain; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - psychology; Brief Report; Cancer; Cancer research; Cancer therapies; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Cognition & reasoning; Cognition - drug effects; Cognition disorders; Cognition Disorders - chemically induced; Cognition Disorders - diagnosis; Fatigue; Fatigue - chemically induced; Fatigue - diagnosis; Female; Hemoglobin; Humans; Investigations; Longitudinal Studies; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medicine; Medicine & Public Health; Memory, Short-Term - drug effects; Middle Aged; Neuropsychological Tests; NMR; Nuclear magnetic resonance; Oncology; Prospective Studies
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-014-3092-6

The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with ( n  = 28) or without chemotherapy ( n  = 37) and healthy controls ( n  = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.