Endocrine treatment-associated cognitive impairment in breast cancer survivors: evidence from published studies

Endocrine-based treatments are the mainstay of therapy for postmenopausal women with breast cancer; yet concern has been raised about potential adverse cognitive effects. We performed a systematic review of the published literature to evaluate whether endocrine-based treatments for breast cancer are associated with changes in cognitive domains and whether these effects are more pronounced with advanced age. An electronic database search was performed. Original investigations that examined the effects of endocrine treatment on cognitive function were identified. Data were abstracted and studies were assessed for risk of bias. A total of 21 unique studies (n = 2398) were identified. Ten were short-term (duration ≤ 2 years) and 11 were long-term (duration > 2 years). Nine (43 %) studies had a sample size ≤100 subjects; 9 (43 %) were longitudinal, with baseline measurement before treatment initiation. No studies were primary randomized clinical trials. While there was heterogeneity in the neuropsychological measures used, tests could be grouped into the cognitive domains that they assessed. Compared to breast cancer or healthy controls, endocrine therapy was associated with impaired performance on neuropsychological testing. No study explored the association between age and changes in cognitive performance. Overall, endocrine therapies were associated with greater cognitive deficits compared to surgical and healthy controls; yet, lack of randomized trial data and heterogeneity in design of many studies limited any definitive conclusions. Despite older women being at highest risk for the development of cognitive impairment, advanced age has not been adequately explored.