Patients and methods Subjects treated for breast cancer with adjuvant chemotherapy remotely (5–10 years previously) were studied with neuropsychologic testing and positron emission tomography (PET), and were compared with control subjects who had never received chemotherapy. [O-15] water PET scans was acquired during performance of control and memory-related tasks to evaluate cognition-related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were acquired to evaluate resting cerebral metabolism. PET scans were analyzed by statistical parametric mapping and region of interest methods of analysis.

Results During performance of a short-term recall task, modulation of cerebral blood flow in specific regions of frontal cortex and cerebellum was significantly altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy-treated subjects differed most significantly from untreated subjects in inferior frontal gyrus, and resting metabolism in this area correlated with performance on a short-term memory task previously found to be particularly impaired in chemotherapy-treated subjects. In examining drug-class specific effects, metabolism of the basal ganglia was significantly decreased in tamoxifen + chemotherapy-treated patients compared with chemotherapy-only breast cancer subjects or with subjects who had not received chemotherapy, while chemotherapy alone was not associated with decreased basal ganglia activity relative to untreated subjects.

Conclusion Specific alterations in activity of frontal cortex, cerebellum, and basal ganglia in breast cancer survivors were documented by functional neuroimaging 5–10 years after completion of chemotherapy.