Abstract and Introduction
Abstract
Objective: Women with breast cancer have been found to have poorer cognitive function before the initiation of systemic adjuvant therapy than their age- and education-matched counterparts. The basis for this may partly include hormone exposure during the course of a woman's life.
Methods: We compared cognitive function between postmenopausal women with breast cancer before the initiation of systemic adjuvant therapy and healthy age- and education-matched postmenopausal women and examined whether factors related to lifetime exposure to hormones predicted cognitive function before therapy.
Results: We found that, compared with healthy women, women with breast cancer had poorer memory (P = 0.05) and attention (P = 0.006). Controlling for the covariates age and estimated verbal intelligence, we found that factors related to greater lifetime hormone exposure (oral contraceptive use, greater years since menopause, and longer duration of hormone therapy) predicted cognitive function (executive function, verbal learning and memory, attention, psychomotor efficiency, and visual sustained attention) in women with and without breast cancer but did not explain the differences in cognitive function observed at pretreatment in women with breast cancer.
Conclusions: Other factors may explain the poorer pretreatment cognitive function in women with breast cancer, including persistent effects of surgical operation and anesthesia, sleep problems, and tumor-related factors. Additional studies are needed to explicate the basis of poorer pretherapy cognitive function in this population.
Introduction
Changes in cognitive function in women with breast cancer are frequently attributed to adjuvant therapy. The basis for these changes is likely to be multifactorial and is not completely understood. Moreover, results of longitudinal studies that include pretreatment cognitive assessments indicate that, before the start of adjuvant therapy, some women with breast cancer perform more poorly in cognitive measures than their healthy counterparts, suggesting that other factors influence pretreatment cognition.
Multiple factors may predict pretreatment cognitive function in women with breast cancer, including their lifetime exposure to hormones. Substantial biological evidence indicates that estrogen has a positive influence on brain functioning, although, clinically, evidence for a relationship between estrogen and cognitive function is conflicting. The basis for this conflicting evidence may partly reflect a failure to take into account estrogen exposure factors during the course of a woman's life. The influence of estrogen on the brain seems to begin prenatally and persists throughout a woman's life. Endogenous factors (such as parity, age at menarche, and menopause or, collectively, the number of reproductive years) and exogenous factors (such as oral contraceptive use and hormone therapy [HT] use) all contribute to a woman's lifetime exposure to hormones. Cognitive benefits of estrogen exposure may be specific for certain domains of cognitive function. Results of several studies suggest that greater lifetime exposure to estrogen is associated with better verbal memory in healthy women. Others have found that lifetime estrogen exposure is associated with better global cognitive function, psychomotor efficiency, concentration, and verbal attention in women.
Although estrogen exposure seems to have cognitive benefits for women, exposure to hormones, such as estrogen, also places them at greater risk for breast cancer. However, a closer examination of specific factors that influence estrogen exposure during the course of a woman's life may reveal that individual estrogen exposure factors have differential effects on cognitive function. Examining the influence of the differential effects of estrogen exposure on cognitive function may help to explain pretreatment cognitive function in women with breast cancer. Thus, we examined cognitive function in women with breast cancer before their initiation of systemic adjuvant therapy and compared them with healthy women to determine whether factors related to a lifetime exposure to hormones were associated with poorer cognitive function before therapy. We hypothesized that factors associated with less estrogen exposure (shorter reproductive life and parity) are associated with poorer cognitive function, particularly verbal memory, in women with breast cancer compared with healthy women and, conversely, factors associated with greater estrogen exposure (oral contraceptive use and HT use) are associated with better cognitive function, particularly verbal memory, in women with breast cancer.