Abstract P3-11-01: Prospective study of cognitive function in women with early stage breast cancer: Predictors of cognitive decline and relationship to cognitive complaints
Authors: Heflin LH , Fang S , DeLuca A , Melisko MM , Moasser M , Park JW , Chien AJ , Munster P , Landau SM , Kramer JH , Jagust WJ , Rugo HS 
Published: August 2014

Abstract
Background: Cognitive complaints are common among women receiving adjuvant therapy (Rx) for early stage breast cancer (ESBC). Longitudinal prospective data is needed to understand cognitive complaints and decline. We conducted a prospective trial to evaluate the effects of chemotherapy (CTX) and hormone therapy (HRx) on brain and cognitive function in patients with ESBC using objective & subjective tests as well as MRI/PET imaging.
Methods: Eligibility included female patients planning to receive adjuvant Rx for ESBC. Patients were enrolled in 3 treatment groups: CTX, CTX and HRx, and HRx, with a 4th no disease age and education matched control group. Patients underwent a battery of objective and subjective cognitive tests before start of Rx, 1 month after CTX or 5 months after start of HRx (FU1), then 9 months (FU2) and 18 months (FU3) after Rx. Brain MRI, PET & serum estradiol (E) were performed at baseline, FU1 & FU3.
Results: 81 patients were enrolled as follows: 14 CTX, 33 CTX & HRx, 22 HRx, and 12 control. 90% completed FU1, 72% FU2, & 62% FU3, with 29 patients waiting to complete testing. Demographics were similar between groups: median age 54, 78% Caucasian. At each FU, approximately 25% of patients showed cognitive decline using a reliable change index; 51% showed decline at ≥ 1 time point, primarily in tests of executive function & verbal memory. 62 - 77% of patients who declined later stabilized or improved. Compared to controls, receipt of HRx (OR 4.94, p = .004) but not serum E, menopausal status, CTX, demographic factors, depression, or fatigue, were significant predictors of decline at any time point. Rx group did not predict cognitive complaints (FACT-Cog). At FUP1, depression, fatigue, and decline in letter fluency predicted overall cognitive complaints, but HRx did not. Cognitive complaints were predicted by domain-specific cognitive decline: memory decline predicted memory complaints, and verbal fluency decline predicted verbal fluency complaints, even after controlling for depression and fatigue. Additional analyses will be presented as more patients complete follow-up testing.
Conclusion: Decline in cognitive function is common in patients receiving adjuvant Rx for ESBC. Ongoing HRx was a risk factor for worse cognitive function, but not for perceived cognitive problems. Other Rx and patient related factors did not predict decline. Perceived cognitive problems were predicted by depression, fatigue, and letter fluency decline, with specific cognitive complaints predicted by domain-specific declines. Patients should be aware that HRx may be a risk factor for cognitive decline, while depression, fatigue, and cognitive decline predicted cognitive complaints. Intervention studies, including assessment for depression and fatigue, should be offered to patients who complain of cognitive changes and particularly to patients treated with HRx.
Funding: NIH R01 1AG025303-01A2.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-11-01.