PD04-08: Altered Neurocognitive Responses Prior to Adjuvant Therapy for Breast Cancer: A Functional MRI Analysis of the Impact of Worry and Fatigue.

Background: The underlying brain mechanisms of altered cognitive function associated with adjuvant chemotherapy for breast cancer, commonly designated “chemobrain”, have yet to be determined. Recent research indicates that compromised cognitive function may already exist prior to treatment, adding to the complexity of determining the true impact of adjuvant chemotherapy on brain function. We examined whether two common symptoms associated with breast cancer diagnosis, worry and fatigue, might influence neurocognitive responses during functional magnetic resonance imaging (fMRI) before adjuvant therapy. Methods: Seventy five women (29–75 years) awaiting either adjuvant chemotherapy (n=25) or radiation therapy (n=25) for localized breast cancer and age-matched controls without breast cancer (n=25) were enrolled. Participants performed a verbal working memory task (VWMT) with varying levels of demand for cognitive control during fMRI scanning and provided self-reports of worry and fatigue after scanning. Imaging data were analyzed using the general linear model implemented in SPM5; comparative statistics were used to determine group differences in self-report and behavioral measures. Results: In general, the pre-chemotherapy group showed compromised cognitive functioning relative to the other groups. Specifically, they reported higher worry than the pre-radiation therapy (p=.036) and control (p=.047) groups. The pre-chemotherapy group also identified greater fatigue than controls (p=.04); the pre-radiation group reported a fatigue level between the other two groups. In the VWMT, the pre-chemotherapy group was less accurate than controls (p=.05), while the mean accuracy for the pre-radiation group again fell between these two groups. fMRI results showed that the control group selectively increased recruitment of executive control brain regions including the left inferior frontal gyrus (LIFG) and the anterior cingulate cortex (ACC) in response to high vs. low demand conditions. However, recruitment of LIGF and ACC by the control group was greater than that by both the pre-chemotherapy (p=.01 and p=.003 respectively) and the pre-radiation groups (p=.027 and p=.02 respectively). Overall, higher fatigue was correlated with failure to increase recruitment of the LIFG and ACC in high vs. low demand conditions (p=.002 and p=.078 respectively). Greater worry was correlated with failure to suppress task-irrelevant activation of default network regions, particularly the posterior cingulate cortex, in high vs. low demand conditions, and with lower accuracy in the VWMT (p=.01). Thus, fatigue and worry made independent contributions to altered neurocognitive responses prior to any adjuvant treatment. Discussion: These findings suggest that women awaiting adjuvant chemotherapy are vulnerable to compromised cognitive functioning, specifically in the domains of attention and working memory, related to higher worry and fatigue. Worry and fatigue may contribute to the cognitive impact often attributed to adjuvant chemotherapy. Therapeutic interventions to counteract worry and fatigue hold potential for optimizing cognitive function prior to adjuvant treatment for breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-08.