Results from a retrospective study of a large cohort of women with breast cancer suggested that use of hormone modifying therapy (HMT) with tamoxifen or an aromatase inhibitor was associated with a decreased risk of developing particular age-related neurodegenerative diseases, such as dementia and Alzheimer disease. These findings were published in JAMA Network Open.1

Although a number of studies have evaluated the potential impact of HMT, such as selective estrogen receptor modulators, tamoxifen, and raloxifene, as well as steroidal (ie, exemestane) and nonsteroidal aromatase inhibitors (ie anastrozole, letrozole), on cognitive functioning when administered over a long-term period to women with hormone receptor-positive breast cancer, findings from these studies ranged from showing no such effects to significant cognitive deficits.2

In this context, the study authors noted that “as we advance in our abilities to prevent, treat, and cure cancer, discussions around optimal care will need to include understanding the long-term outcomes of therapy selection for age-related.”1

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In this study, data covering the period from January 1, 2007, to March 31, 2017, from women with a diagnosis of breast cancer were accessed from a claims database that predominantly included patients residing in the southeastern portion of the United States. Eligibility requirements for study inclusion included age 45 years or older and active enrollment in the database for at least 6 months prior to and 3 years following breast cancer diagnosis. Assessments for the diagnosis of neurodegenerative diseases were initiated at 1 year following breast cancer diagnosis. Propensity score analysis was used to reduce potential bias due to confounding variables associated with each type of neurodegenerative disease investigated.

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Of the 57,843 patients meeting eligibility criteria, 18,126 patients with a mean age of 76.2 years had undergone HMT, whereas the remaining 39,717 patients not treated with HMT had a mean age of 76.8 years.

At a mean follow-up of 5.5 years, propensity-score matched analyses showed the percentages of patients with Alzheimer disease were 4.9% and 6.0% in those receiving HMT vs not (relative risk [RR], 0.82; 95%CI, 0.75-0.90; P <.001). A similar reduction in the risk of dementia with HMT (10.4%) was also observed when this group was compared with the non-HMT group (11.8%; RR, 0.88; 95%CI, 0.83-0.93; P <.001).

Furthermore, when the data were analyzed according to specific HMT agent, patients receiving tamoxifen or an aromatase inhibitor had significant reductions in risk of Alzheimer disease compared with those not receiving HMT, whereas those receiving raloxifene did not.

Similar findings were observed with respect to dementia when these 2 groups of patients were compared according to type of HMT received. In addition, reductions in risk of both Alzheimer disease and dementia were found to be greater for those receiving steroidal compared with nonsteroidal aromatase inhibitor therapy.


1. Branigan GL, Soto M, Neumayer L, Rodgers K, Diaz Brinton R. Association between hormone-modulating breast cancer therapies and incidence of neurodegenerative outcomes for women with breast cancer. JAMA Netw Open. 2020;3(3):e201541.

2. Biro E, Kahan Z, Kalman J, et al. Cognitive functioning and psychological well-being in breast cancer patients on endocrine therapy. In Vivo. 2019;33:1381-1392.