606 Background: There is recent evidence of cognitive sequelae from chemotherapy for breast cancer. It has been suggested that chemotherapy affects the white matter of the brain. The purpose of this pilot project was to test the hypothesis that chemotherapy affects the frontal white matter more than the posterior white matter, using Diffusion Tensor Imaging (DTI). Methods: Ten patients with breast cancer (3 patients with stage I, 5 patients with stage II, and 2 patients with stage III) who reported changes in cognitive function after chemotherapy, served as participants. Five patients had received Adriamycin and cytoxan (AC) for 4 cycles and 5 patients had received AC followed by 4 cycles of a taxane. The patients were an average of 22 months post chemotherapy. All participants were screened for other health problems that could potentially affect cognition and brain structure. Seven healthy, age, education, and IQ matched women served as controls. DTI was measured in the axial plane with 30 4mm slices and 25 directions at 3Tesla. All analyses were performed blind to group membership. Fractional Anisotropy (FA) was calculated in the genu and splenium of the corpus callosum. Data were analyzed in a mixed two-way ANOVA. Participants also completed a measure of complex attention and speeded processing (Digit Symbol). Results: There was excellent interrater reliability of the FA measurements (0.96). There was a significant interaction of group x brain regions, F(1, 15)=4.85, p<0.05, with lower FA in the genu, but no difference between groups for FA in the splenium. Digit Symbol performance was significantly lower in patients than controls, F(1, 15)=8.65, p<0.05. FA in the genu was significantly correlated (r=0.46, p<0.05) with Digit Symbol performance. Conclusions: The results of this study suggest that chemotherapy for breast cancer causes changes in the frontal white matter of the brain which may lead to cognitive dysfunction. Prospective studies are warranted. No significant financial relationships to disclose.