Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study.
Persistent cancer-related fatigue (PCRF) is one of the most troubling side-effects of breast cancer (BC) treatment. One explanatory model for PCRF is sickness behavior, which is a set of adaptive responses including sleepiness and depressed mood in reaction to an inflammatory trigger. Prior research has investigated differences in inflammatory cytokines between fatigued and non-fatigued BC survivors, but no study has examined differences in brain metabolites. Differences in inflammatory markers, and brain metabolites using proton magnetic resonance spectroscopy were evaluated within 16 fatigued and 13 non-fatigued BC survivors. Fatigued BC survivors had significantly higher ratios of two markers derived from brain metabolites; namely (a) creatine, normalized to total creatine (creatine + phosphocreatine (Cr/tCr)) ratio (P = 0.03) and (b) glutamate + glutamine (Glx) to N-acetyl-aspartate (NAA) ratio (P = 0.01) in the posterior insula compared to non-fatigued breast cancer survivor. Further, serum IL-6 was increased in fatigued women compared to non-fatigued women (P = 0.03), Using receiver operator curves (ROC) we determined that the posterior insula Glx/NAA ratio was the best predictor of fatigue with an overall area under the receiver operating characteristic curve (AUROC) of 79%, with a sensitivity of 81% and a specificity of 69%. However, posterior insula Glx/NAA, Cr/tCr and serum IL-6 were not significantly correlated with one another implying the possibility of independent biological mechanisms for PCRF rather than an interrelated mechanism as represented by the sickness behavior model. This study provides novel preliminary evidence of several distinct neurobiological changes in the posterior insula associated with PCRF in BC survivors. Future, longitudinal studies are needed to explore these distinct biological phenomena where changes through time in peripheral immune markers and brain metabolites are examined to determine if they correlate with changes in fatigue.
Department of Family Medicine, University of Michigan, 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA, szick@umich.edu.
Suzanna Maria
SM
Zick
Heather
H
Zwickey
Lisa
L
Wood
Bradley
B
Foerster
Tohfa
T
Khabir
Benjamin
B
Wright
Eric
E
Ichesco
Ananda
A
Sen
Richard Edmund
RE
Harris
D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001943:Breast Neoplasms / Q000150:complications* / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D005221:Fatigue / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D010725:Phosphocreatine / Q000378:metabolism; D010865:Pilot Projects; D011379:Prognosis; D066244:Proton Magnetic Resonance Spectroscopy; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D017741:Survivors
D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D010725:Phosphocreatine; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D003401:Creatine