Changes in regional brain metabolism following initial therapy for breast cancer

Objectives To examine effects of endocrine and chemotherapy on brain metabolism in newly diagnosed breast cancer patients in response to growing recognition that a sizeable minority of these patients report and/or demonstrate cognitive compromise.

Methods Subjects(n=15) recently diagnosed with breast cancer and not yet on endocrine therapy were recruited; 10 had recently completed adjuvant chemotherapy treatment while 5 had none. Half of the subjects of each group underwent endocrine therapy during the year subsequent to initial therapy. Each subject underwent 7 PET scans at baseline and again one year later: 6 [O-15]water PET scans during performance of control and memory tasks to evaluate cognition related cerebral blood flow, and an FDG PET scan to assess resting brain metabolism. Regional brain activity was analyzed by standardized volume of interest and statistical parametric mapping methods.

Results In the adjuvant chemotherapy group, subjects who also underwent endocrine therapy(n=5) experienced increased bilateral medial prefrontal metabolism(p=0.001) after one year, while subjects without endocrine therapy(n=5) experienced increased occipital/superior cerebellar metabolism(cluster-corrected p=0.001). Subjects undergoing endocrine therapy also demonstrated increased cerebral blood flow in the frontal cortex (including Broca’s area)(p<0.0005) during a short term memory task. Pooling together all subjects who underwent chemotherapy, there was an increase in left superior temporal(cluster-corrected p<0.0005) and right inferior frontal(p<0.0005) metabolism after one year that was not seen in the subjects who did not undergo chemotherapy.

Conclusions Endocrine and chemotherapy were associated with regionally specific changes in resting metabolism and activation in brains of newly diagnosed breast cancer patients. These changes may underlie the differential cognitive effects reported by the patients following therapy.

Research Support Grant:NCI RO1-CA109650&Breast Cancer Research Foundatio