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Lifetime hormone exposure and cognition in postmenopausal women with breast cancer.

B reast cancer risk increases after menopause. The American Cancer Society in 2011 estimated that 80% of breast cancers are diagnosed in women aged 50 years or older. As women live to older ages after breast cancer treatment, quality-of-life issues have become important to understand. One common complaint before, during, and after breast cancer treatment involves cognitive changes from precancer levels of functioning, sometimes referred to by survivors as Bchemobrain.[ Recent research has focused on describing changes in cognitive functioning after chemotherapy. Although longitudinal studies have shown that chemotherapy may impair cognition in some women, they have also shown that women with breast cancer have decreased cognitive performance at baseline/prechemotherapy assessment compared with healthy controls. Thus, understanding the factors underlying decreased cognition in women with breast cancer is important in interpreting further decreases after chemotherapy and in preventing and treating cognitive changes. In an effort to understand the mechanisms underlying cognitive changes after cancer diagnosis, it is important to examine the role of hormones, in particular gonadal steroids, in cognition. Prior literature has shown the importance of gonadal steroids in cognition across the life span and in breast cancer development. A large body of literature shows the influence of hormones on cognition in postmenopausal women. In addition, greater lifetime estrogen exposure is related to increased breast cancer risk. In this issue of Menopause, Bender et al examined the influence of lifetime hormone exposure on cognition in postmenopausal women with breast cancer. As breast cancer is primarily a disease of older women, issues of cognitive aging are combined with the cognitive effects of cancer and cancer treatments that perhaps impair cognition in postmenopausal women to a greater extent than in younger women. Thus, understanding how hormones affect cognition and interact with breast cancer and cancer treatment is important as women are living well into older ages as breast cancer survivors. The brain is a major target of circulating gonadal steroids, and lifetime hormone exposure has implications for cognitive functioning. A number of clinical and preclinical studies have linked gonadal steroids and cognition. Studies have shown benefits of increased lifetime hormone exposure on cognition. In addition, some studies have found decreased cognitive performance in specific cognitive domains, including memory, attention, problem solving, and motor skills, after menopause (when circulating estradiol levels dramatically decrease from premenopausal levels). Other studies have not found objective changes in cognition after menopause. Evidence indicates that postmenopausal estrogen therapy maintains the premenopausal levels of cognitive functioning. However, a number of studies have shown that postmenopausal hormone treatment has no benefit on cognition. Studies published as part of the Women’s Health Initiative examined the impact of conjugated estrogens (CEE) plus progestin and conjugated estrogens alone on postmenopausal women and found that combined hormone treatment in older postmenopausal women increased breast cancer risk and dementia. No study has thus far considered the relationship between hormone exposure before menopause, cognition, and cancer. Women with cancer have long reported adverse effects of cancer and cancer treatments on cognition, and a number of studies have shown negative effects of chemotherapy on cognition. Much of the work has focused on women with breast cancer and has found that women report subjective complaints of cognitive impairment and show objective impairment during neuropsychological testing. Interestingly, in longitudinal studies that assessed cognition before and after chemotherapy, women with breast cancer performed worse than noncancer controls at prechemotherapy assessment. Bender et al examined the role of lifetime hormone exposure in this pretreatment difference in cognitive performance between postmenopausal women with breast cancer and controls. They proposed that greater lifetime exposure to hormones might underlie differences in cognition between women with cancer and women without breast cancer. Lifetime hormone exposure is measured by endogenous factors such as age at menarche, age at menopause, and parity, as well as exogenous factors such as hormonal birth control and postmenopausal hormone therapy. In healthy women, greater lifetime estrogen exposure was associated with better verbal memory. Bender et al hypothesized that differences in lifetime estrogen exposure are related to pretreatment cognitive impairment in women with breast cancer, such that greater hormone exposure would be related to better cognitive performance, in general, and better verbal memory, in particular. Bender et al examined cognition in 264 postmenopausal women with breast cancer before they began chemotherapy treatment and compared it with cognition in 95 healthy controls. All participants performed a neurocognitive test battery