title: A feasibility study exploring the role of pre-operative assessment when examining the mechanism of 'chemo-brain' in breast cancer patients.
abstract: BACKGROUND
  Women receiving chemotherapy treatment for breast cancer may experience problems with their memory and attention (cognition), which is distressing and interferes with quality of life. It is unclear what causes or contributes to the problems they report: psychological distress, fatigue, coping style, or specific biological changes for example to pro inflammatory cytokines. Research shows however, that approximately a third of women with breast cancer perform poorly on tests of cognition before commencing chemotherapy. We aimed to examine the acceptability and relevance of pre-surgical assessments (bloods, brain imaging, cognitive tests and self-report questionnaires) when investigating the phenomenon of 'chemo-brain' and investigate whether inflammatory markers mediate chemotherapy-induced neuropsychological impairments in women treated for breast cancer.
  
  
  METHODS
  Women with early stage breast cancer completed neuropsychological and quality of life assessments at T1 (pre-surgery), T2 (post-surgery before chemotherapy) and T3 (6 months later). Blood cytokine levels were measured at the same time points and brain imaging was performed at T1 and T3.
  
  
  RESULTS
  In total, 14/58 women participated (8 chemotherapy, 6 non-chemotherapy). Prior to the start of chemotherapy a decline in cognitive performance compared to baseline was observed in one participant. At T3 women who received chemotherapy reported poorer quality of life and greater fatigue. Increases in soluble tumour necrosis factor receptor II (sTNFRII), interleukin-6, interleukin-10 and vascular endothelial growth factor occurred post chemotherapy only. Levels of sTNFRII were inversely correlated with grey matter volume (GMV) of the right posterior insula in both groups. At T3, the chemotherapy group displayed a greater reduction in GMV in the subgenual and dorsal anterior cingulate, and the inferior temporal gyrus.
  
  
  CONCLUSIONS
  Pre-operative recruitment to the study was challenging; however, the lack of significant changes in blood cytokine levels and neuropsychological tests at T2 implies that post surgery may be a valid baseline assessment, but this needs further investigation in a larger study. The preliminary results support the hypothesis that chemotherapy induced fatigue is mediated by a change in peripheral cytokine levels which could explain some symptoms of 'chemo brain' experienced by patients.
authors.affiliation: Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Jenkins
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Ryan
authors.initials: R
authors.lastname: Thwaites
authors.affiliation: Clinical Imaging Sciences Centre (CISC), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sacre
authors.affiliation: Clinical Imaging Sciences Centre (CISC), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Harrison
authors.affiliation: Clinical Imaging Sciences Centre (CISC), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Hefina
authors.initials: H
authors.lastname: Whiteley-Jones
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Mullen
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Giselle
authors.initials: G
authors.lastname: Chamberlain
authors.affiliation: Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Davies
authors.affiliation: Brighton and Sussex University Hospitals NHS Trust, Brighton, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Zammit
authors.affiliation: Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Matthews
authors.affiliation: Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Harder
keywords: Brain imaging; Breast cancer; Cognitive function; Cytokines; Fatigue; Quality of life