Breast cancer therapies reduce risk of Alzheimer's disease and promote estrogenic pathways and action in brain

Gregory L Branigan; Georgina Torrandell-Haro; Shuhua Chen; Yuan Shang; Samantha Perez-Miller; Zisu Mao; Marco Padilla-Rodriguez; Helena Cortes-Flores; Francesca Vitali; Roberta Diaz Brinton

doi:10.1016/j.isci.2023.108316

Breast cancer therapies reduce risk of Alzheimer's disease and promote estrogenic pathways and action in brain

iScience. 2023 Oct 24;26(11):108316. doi: 10.1016/j.isci.2023.108316. eCollection 2023 Nov 17.

Authors

Gregory L Branigan^{1

2

3}, Georgina Torrandell-Haro^{1

2}, Shuhua Chen¹, Yuan Shang¹, Samantha Perez-Miller¹, Zisu Mao¹, Marco Padilla-Rodriguez¹, Helena Cortes-Flores¹, Francesca Vitali^{1

4}, Roberta Diaz Brinton^{1

2

5}

Affiliations

¹ Center for Innovation in Brain Science, University of Arizona; Tucson AZ, USA.
² Department of Pharmacology, University of Arizona College of Medicine; Tucson AZ, USA.
³ Medical Scientist Training Program, University of Arizona College of Medicine; Tucson AZ, USA.
⁴ Center of Bioinformatics and Biostatistics, University of Arizona College of Medicine; Tucson AZ, USA.
⁵ Department of Neurology, University of Arizona College of Medicine; Tucson AZ, USA.

Abstract

Worldwide, an ever-increasing number of women are prescribed estrogen-modulating therapies (EMTs) for the treatment of breast cancer. In parallel, aging of the global population of women will contribute to risk of both breast cancer and Alzheimer's disease. To address the impact of anti-estrogen therapies on risk of Alzheimer's and neural function, we conducted medical informatic and molecular pharmacology analyses to determine the impact of EMTs on risk of Alzheimer's followed by determination of EMT estrogenic mechanisms of action in neurons. Collectively, these data provide both clinical and mechanistic data indicating that select EMTs exert estrogenic agonist action in neural tissue that are associated with reduced risk of Alzheimer's disease while simultaneously acting as effective estrogen receptor antagonists in breast.

Keywords: Cancer; Neurology; Therapy.

Abstract

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