Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review

Abstract

Breast cancer treatment can induce alterations in blood- and neuroimaging-based markers. However, an overview of the predictive value of these markers for cognition is lacking for breast cancer survivors. This systematic review summarized studies of the last decade, using the PubMed database, evaluating blood markers, and the association between blood- or structural neuroimaging markers and cognition across the chemotherapy trajectory for primary breast cancer, following PRISMA guidelines. Forty-four studies were included. Differences were observed in all blood marker categories, from on-therapy until years post-chemotherapy. Associations were found between cognitive functioning and (1) blood markers (mainly inflammation-related) during, shortly-, or years post-chemotherapy and (2) white and gray matter metrics in frontal, temporal and parietal brain regions months up until years post-chemotherapy. Preliminary evidence exists for epigenetic and metabolic changes being associated with cognition, only after chemotherapy. This review demonstrated time-dependent associations between specific blood-based and structural neuroimaging markers with cognitive impairment in patients with breast cancer. Future studies are encouraged to include both neuroimaging- and blood markers (e.g. of neuronal integrity, epigenetics and metabolism) to predict long-term cognitive effects of chemotherapy.

Keywords: Biological markers; Breast cancer; Chemotherapy; Cognitive impairment; Neuroimaging.

Fig. 1

PRISMA flow chart.

Fig. 2

Schematic overview of maximum percentage of patients scoring cognitive impaired or those reporting complaints; blood markers showing alterations over time and blood and neuroimaging markers showing associations with cognitive score or complaints, all for chemotherapy-treated patients. Note. Patients scoring cognitive impaired or reporting complaints were both defined based on (study-specific) norm scores of cross-sectional findings from studies included in this review [14,20,25,31,34,[37], [38], [39]]. Red = blood marker being altered at a given time point over the course of chemotherapy, blue = blood marker and/or neuroimaging metric showing an association with cognitive score at a given time point. White = no changes or association at a given time point. Fading of colors indicates transitioning to other time point, not strength of associations. Short-term = assessment within one week to four months post-chemotherapy. Long-term = assessment within six months to 20 years post-chemotherapy. DWI = diffusion weighted imaging, T₁W = anatomical T₁ weighted imaging, ¹H-MRS = proton magnetic resonance spectroscopy, ¹⁸F-FDG-PET = metabolic fluor-18 fluorodeoxyglucose positron emission tomography.