Is Baseline Brain White Matter Microstructure Associated With Cognitive Decline After Chemotherapy for Breast Cancer?

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In a Dutch study reported in the Journal of Clinical Oncology, de Ruiter et al found that white matter microstructure at baseline was associated with cognitive decline after chemotherapy for breast cancer.

Study Details

The study included 49 patients with breast cancer who received anthracycline-based chemotherapy, 39 patients with breast cancer who did not receive chemotherapy, and 37 control participants without cancer. Neuropsychological tests were administered before and at 6 months, 2 years, and 3 years after chemotherapy and at matched intervals in participants who did not receive chemotherapy. Fractional anisotropy (FA; a measurement of fiber density, axonal diameter, and myelination in white matter) from magnetic resonance diffusion tensor imaging was used to assess white matter microstructure in all study participants, with assessment performed before treatment in the chemotherapy group.

Key Findings

In multivariate analysis including baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient, low FA at baseline was an independent predictor of cognitive decline at 6 months (P = .013) and 3 years (P < .001) after chemotherapy in the chemotherapy group. FA was not associated with cognitive decline in the no-chemotherapy group or the no-cancer control group.

Voxel-wise diffusion tensor imaging analyses that assessed white matter microstructure in specific nerve tracts showed involvement of tracts essential for cognitive function in the chemotherapy group, including inferior, middle, and superior longitudinal fascicule (visual cognition, language, attention, and memory); inferior fronto-occipital fasciculus (visual processing and memory); cerebral peduncle (dexterity); and thalamic radiations (attention).  

The investigators concluded, “Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for breast cancer. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.”

Michiel B. de Ruiter, PhD, of the Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Dutch Cancer Society. For full disclosures of the study authors, visit

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