Abstract 2654: A prospective study of the effects of adjuvant chemotherapy (CT) on cognition and brain function in breast cancer patients
Authors: Alicia Barr, William Collier, Linda Piacentine, Kelli Douville, Sally Durgerian, Peter LaViolette, David Sabsevitz, Kathleen Schmainda, Christopher R. Chitambar, Alan Bloom
Journal: Cancer Research (2012)

Abstract There is an accumulating body of literature reporting that cognitive deficits, possibly long lasting, including lack of concentration, short-term memory loss and difficulties in multitasking are observed in patients receiving chemotherapy (CT) (“chemobrain”). We have used functional magnetic resonance imaging (fMRI) to determine the nature of the changes in brain function that underlie the cognitive deficits that can result from CT. This research was carried out prospectively in women being treated with adjuvant CT for early-stage breast cancer (BC). Methods: Seven healthy aged-matched control subjects (No CT) and six subjects with BC took part in this study undergoing functional fMRI scanning on a 3.0T scanner prior to initiating CT and after receiving their fourth cycle of anthracycline-based CT. Task activation (n-back) and resting-state functional connectivity (fC) scans were carried out. The N-back letter task is a continuous performance task having 3 levels of increasing cognitive load designed to probe regions of the brain activated by attention and working memory. Resting-state fC measures spontaneous low frequency oscillations in MR signal in brain and is used to create maps of fC among brain regions. Results: There were no significant differences in n-back task performance between the CT group and controls. However, significant differences (p≤0.05) in task activation and fC between the two subjects groups were observed. N-back task activation was significantly greater in the BC group compared with controls in right inferior frontal gyrus and right cerebellum. There were significant interactions between subject group and cognitive load within right inferior parietal and left inferior occipital cortex. The default mode network consists of interconnected regions of the brain that are active while the subjects are at rest and reduce activity when subjects perform specific tasks. Within this network, the BC group has significantly less deactivation during task compared to controls. There were also differences between the groups in resting-state fC. Using the left amygdala as a seed region, changes in fC were seen in the pre-chemo scans of the BC group compared to the controls. The BC subjects showed a 185% increase in intraregional fC and increased fC with the superior temporal gyrus, an area along with the amygdala that is activated by emotional stimuli. These changes in fC may be due to increased stress response in BC subjects. After four sessions of CT the BC group showed significant decreases in fC between the amygdala and the parahippocampal gyrus, an area involved in encoding and retrieving memories. This decrease in functional connectivity along with alterations in brain activation by cognitive tasks may play a part in the memory and other cognitive complaints associated with cancer and CT and may inform the search for strategies to reduce CT associated cognitive dysfunction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2654. doi:1538-7445.AM2012-2654