A hormone-modulating therapy (HMT) used to treat breast cancer was linked to a 7% lower risk of developing Alzheimer’s or related dementias later in life, according to a new study published today in JAMA Network Open.
The study, one of the largest of its kind, found that while HMT was associated with protection against developing dementia overall, that association decreased with age and varied by race.
“Our findings underscore the importance of considering individual patient factors when we prescribe medications or develop breast cancer treatment plans,” said senior author Francesmary Modugno, Ph.D., MPH, professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and a member of the Magee-Womens Research Institute and UPMC Hillman Cancer Center. “There is no one-size-fits-all approach. We need to think about each individual patient to optimize outcomes and minimize risks.”
About two-thirds of all breast cancer patients have tumors that are hormone receptor-positive, meaning they grow in response to estrogen or progesterone. For these patients, HMT can inhibit tumor growth by blocking the binding of hormones to these receptors. While the use of HMT has been linked to increased survival rates, there is conflicting evidence about whether it increases or decreases the risk of developing Alzheimer’s and related dementias (ADRD) — debilitating conditions characterized by memory loss, mood or behavioral changes, and difficulty with thinking, problem-solving, and reasoning.
To improve understanding of the risk of ADRD after HMT in breast cancer patients, Modugno collaborated with lead author Chao Cai, Ph.D., an assistant professor at the University of South Carolina College of Pharmacy. They used a national database of individuals aged 65 and older to identify women diagnosed with breast cancer between 2007 and 2009 who had no prior ADRD diagnosis and had not used HMT prior to their breast cancer diagnosis.
Of 18,808 patients who met the criteria, 66% had received HMT within three years of their diagnosis, and 34% had not. During an average follow-up of 12 years, 24% of HMT users and 28% of non-HMT users developed ADRD.
To calculate the risk of developing ADRD, researchers accounted for the risk of death associated with increasing age and duration of HMT exposure. They found that while the use of HMT was associated with an overall reduction in the relative risk of developing ADRD, HMT’s protective effect was most pronounced in patients aged 65 to 69 and decreased with age. Specifically, among patients older than 80, HMT users had an increased risk of ADRD.
“Our study suggests that younger women may benefit more from HMT in terms of a lower risk of developing Alzheimer’s or other dementias,” Cai said. “For women aged 75 and older, especially those who identified as white, HMT’s benefit decreased. This suggests that the timing of HMT initiation is critical and treatment plans should be tailored to the patient’s age.”
For Black women aged 65 to 74 who used HMT, the relative risk of developing ADRD decreased by 24%. After age 75, this risk dropped to 19%. For white women aged 65 to 74 who used HMT, the risk of developing ADRD decreased by 11%, but this positive association disappeared after age 75.
