In this multimodal neuroimaging study, observations indicate the likely involvement of neuroinflammatory processes in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly following chemotherapy for early-stage breast cancer.

• This study included 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls, to investigate the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes.

• Total or localized lesion burden did not differ significantly between groups.

• Significantly higher (20–45%) translocator protein uptake was noted in juxtacortical lesions vs normal appearing white matter in both cancer groups, but only persisted for chemotherapy-treated patients post-partial volume correction.

• There was no association of neurofilament light-chain serum levels with total lesion volume or tracer uptake in juxtacortical lesions.