Hormone modulating therapy (HMT) for breast cancer is associated with a 7% lower risk of developing Alzheimer’s disease and related dementia (ADRD) later in life, according to a new study.
“Our findings emphasize the importance of considering individual patient factors when prescribing medications or developing treatment plans for breast cancer,” said senior author Francesmary Modugno, Ph.D., M.P.H., professor at the University of Pittsburgh and member of Magee-Womens Research Institute and UPMC Hillman Cancer Center.
The study revealed that while HMT is linked with a general protection against dementia, this effect diminishes with age and varies by race.
Approximately two-thirds of breast cancer patients have hormone receptor-positive tumors that grow in response to estrogen or progesterone. HMT can slow tumor growth by preventing hormones from binding to certain receptors. However, there has been conflicting evidence about whether HMT affects the risk of developing ADRD.
To better understand this risk, Modugno and lead author Chao Cai, Ph.D., assistant professor at the University of South Carolina, analyzed data from a federal database of women aged 65 and older diagnosed with breast cancer between 2007 and 2009, who had no prior ADRD diagnosis or history of HMT use before their cancer diagnosis.
Among the 18,808 patients studied, 66% received HMT within three years of their diagnosis. Over an average follow-up period of 12 years, 24% of HMT users and 28% of non-HMT users developed ADRD.
The researchers found that HMT was associated with a lower overall risk of ADRD, especially in women aged 65 to 69. However, this protective effect decreased with age and was not observed in patients over 80.
“Our study suggests younger women may benefit more from HMT in terms of reduced dementia risk,” said Cai. “The benefits of HMT decreased for women aged 75 and older, particularly for those who identified as white. This highlights the importance of tailoring treatment plans to a patient’s age.”
Black women aged 65 to 74 who used HMT had a 24% reduction in ADRD risk, which dropped to 19% after age 75. White women in the same age range had an 11% reduction in ADRD risk with HMT, but this benefit disappeared after age 75.
“Black women have higher rates of breast cancer and face higher lifetime stress due to structural racism and other factors, which could contribute to worse outcomes,” said Modugno. “The racial disparities in HMT and ADRD risk deserve further investigation.”
The study also found that the risk of developing ADRD varied by the type of HMT used: selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders. Estrogen has neuroprotective effects, and these therapies may influence ADRD risk by mimicking estrogen, affecting estrogen production, or modulating estrogen receptor levels. HMT might also impact beta-amyloid clearance, tau protein stability, and vascular health, all of which are linked to brain health and ADRD risk.
“The relationship between HMT for breast cancer and dementia risk is complex and influenced by multiple factors,” explained Cai. “Ongoing research is needed to further understand this association and provide clearer guidance on HMT use.”
The study was limited to patients over 65. Future research by Cai and Modugno will include younger women who haven’t reached menopause to better understand the link between HMT and dementia risk.
Other contributors to the study were Kaowao Strickland, M.P.H., Sophia Knudsen, Sarah Beth Tucker, and Chandana Sai Chidrala, M.S., all from the University of South Carolina.
