A feasibility study exploring the role of pre-operative assessment when examining the mechanism of 'chemo-brain' in breast cancer patients

Valerie Jenkins, Ryan Thwaites, Mara Cercignani, Sandra Sacre, Neil Harrison, Hefina Whiteley-Jones, Lisa Mullen, Giselle Chamberlain, Kevin Davies, Charles Zammit, Lucy Matthews, Helena Harder, Valerie Jenkins, Ryan Thwaites, Mara Cercignani, Sandra Sacre, Neil Harrison, Hefina Whiteley-Jones, Lisa Mullen, Giselle Chamberlain, Kevin Davies, Charles Zammit, Lucy Matthews, Helena Harder

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.

Keywords: Brain imaging; Breast cancer; Cognitive function; Cytokines; Fatigue; Quality of life.

Figures

Fig. 1
Fig. 1
Levels of circulating cytokines are altered by treatment with chemotherapy. Serum was collected from breast cancer patients being treated with chemotherapy (CT) and those not undergoing chemotherapy (NCT). Serum levels of a sTNFRII, b IL-6, c VEGF, d IL-10, e MCP-1 and f BDNF were measured. Data for eight CT patients and six NCT patients is shown as the mean ± SEM (*p < 0.05; **p < 0.01)
Fig. 2
Fig. 2
Grey matter volume results: two-way ANOVA. The areas of significant group-by-time interaction are highlighted, and overlaid onto a T1-weighted template image. a 2 clusters in the cingulate cortex; b the inferior temporal gyrus cluster
Fig. 3
Fig. 3
Grey matter volume results: correlations with cytokines. The solid coloured areas indicate the localisation of the significant correlation between grey matter volume and IL-6 (a) or sTNFRII (b). The clusters are overlaid onto a T1-weighted template image in standard space
Fig. 4
Fig. 4
Flow diagram of the pre-processing steps in standard voxel-based morphometry

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