OBJECTIVES:

Hormone-modulating therapies (HMTs), including selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), have revolutionized breast cancer (BC) care. Studies have found an altered risk of dementia with HMTs; however, this has not been studied in postmenopausal women with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) BC. Hence, this study evaluated the risk of dementia associated with HMT use among HR+/HER2- BC women.

METHODS:

This nested case-control study utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. The study included women ≥65 years with an incident diagnosis of HR+/HER2- BC as their first and only cancer from 2010-2018. Cases were those who had an incident diagnosis of dementia after 12 months from the BC diagnosis date (cohort entry). Patients without dementia (controls) were matched with cases using variable-ratio matching on age. During the 12-month lookback period, exposure to HMT was evaluated. A multivariable conditional logistic regression model was used to evaluate the risk of dementia with HMT use. The Andersen Behavioral Model was used to conceptualize covariates for the multivariable model.

RESULTS:

This study identified 2,536 cases and 12,680 matched controls based on age±2 with replacement. A significantly higher proportion of cases were exposed to the HMTs than controls (58.52% and 44.68%, p<0.0001). Exposure to HMTs was associated with 86% increased odds of dementia among HR +/HER2- BC patients compared to those without the use of HMT (adjusted odds ratio (aOR)=1.86, 95% confidence interval [CI]=1.69-2.05, p<0.0001) after adjusting for sociodemographic characteristics and clinically relevant factors.

CONCLUSIONS:

Among HR+/HER2- BC patients, the use of HMTs was associated with an increased risk of dementia. More work is needed to understand the role of HMTs, including SERMs and AIs, in age-associated neurodegenerative diseases.