SUMMARY: Cognitive impairment in patients with breast cancer has been frequently attributed to chemotherapy (Chemo Brain) without any data supporting this hypothesis. Utilizing functional magnetic resonance imaging, brain function was tested while the patients were performing a working memory task in the scanner, before adjuvant treatment and then one month after adjuvant treatment. Sixty six breast cancer patients with Stages 0-IIIA were studied and their cognitive function was compared with 32 healthy controls. Patients on treatment were receiving either an anthracyline-based adjuvant chemotherapy regimen (n = 29) or radiotherapy (n = 37). Patients self-reported on levels of cognitive functioning and fatigue after each imaging study. Pretreatment brain imaging revealed decreased functioning in the frontal lobe of the brain (responsible for memory and cognition), compared to the controls and this cognitive impairment was most severe in patients awaiting chemotherapy, whereas the radiotherapy group fell between the pre-chemotherapy and control group. Of Interest, the decreased functioning in the frontal lobe area before treatment predicted the severity of fatigue. Further, those with greater fatigue experienced greater cognitive impairment over time. The authors concluded that the cognitive problems are probably related to worry and fatigue prior to treatment intervention rather than the treatment itself. They recommend identifying patients at risk and early intervention. Cimprich B, Hayes DF, Askren MK, et al. CTRC-AACR San Antonio Breast Cancer Symposium, 2012; Abstract S6-3.