PD04-07: Cognitive Function and Reproductive Hormones in Women Receiving Anastrozole.

Abstract

Abstract Background: The effects of adjuvant hormonal therapy on hormone levels may contribute to deterioration in cognitive function experienced by women with breast cancer. Estrogen receptors are present throughout the central nervous system. Estrogen binding increases ChAT, synaptogenesis and dendritic spine density in the hippocampus and hypothalamus and decreases monoamine oxidase activity. Aromatase inhibitors, such as anastrozole, interrupt estrogen biosynthesis resulting in profound estrogen reductions. We studied whether changes in reproductive hormone levels mediate changes in cognitive function in 3 cohorts of postmenopausal women; women with breast cancer who receive chemotherapy+anastrozole (CA; n=41) or anastrozole only (AO; n=50)] and age and education matched healthy women (n=44). Methods: We assessed cognitive function and reproductive hormones (E2, LH, FSH) before therapy and at 6, 12 and 18 months post-therapy initiation. A battery of neuropsychological measures was used to assess multiple cognitive domains. Using mixed effects modeling, we analyzed changes in hormone levels from pretreatment to 6, 12 and 18 months post-therapy initiation and then explored intercorrelations between changes in hormone levels and cognitive function at all timepoints. Results: Women were an average 59.3 years of age with an average 14.9 years of education. No significant group-by-time effects were found for LH. However, we found significant group by time effects for E2 when comparing CA with controls (p=.0002) and AO with controls (p<.0001) and for FSH when comparing AO with controls (p=.03). We found that E2 declined from pretreatment in the breast cancer groups as follows; CA [E2 declined from pretreatment to immediately post-chemotherapy (p = .09), and at 6 (p=.0002) and 12 (p=.014) months post anastrozole initiation, and AO [E2 declined from pretreatment to 6 (p<.0001), 12 (p=.004) and 18 (p<.0001) months post-anastrozole initiation]. We also found increases in FSH in the AO group from pretreatment to 6 (p=.002) and 12 (p=.05) months. No significant within-group changes for E2, FSH, or LH were observed for controls. For the full sample, the intercorrelations revealed that reductions in E2 were related to poorer psychomotor efficiency from baseline to 18 months post-baseline (rs=.358, p=.02). For the AO group, reductions in E2 were related to poorer executive function (r=.600, p= 002) from 6 to 12 months post-anastrozole initiation and poorer psychomotor efficiency (r=.453, p=.07) from pretreatment to 18 months post-anastrozole initiation. For the CA group, reductions in E2 were marginally significantly related to poorer attention (r=.307, p=.08) from pretreatment to post-chemotherapy; and to poorer executive function from pretreatment to 6 months (r=.446, p=.06) and 12 months (r=.651, p=.03) post-anastrozole initiation. No significant relationships between changes in E2 levels and cognitive function were found in the controls. Conclusions: Reductions in E2 may be related to cognitive deterioration in women with breast cancer. Further examination of these relationships is needed to confirm the results and determine whether these relationships persist through the remainder and after the conclusion of therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-07.