Hormone modulating therapy (HMT) used to treat breast cancer reduces the risk of developing Alzheimer’s disease and related dementia later in life by 7 percent, according to a new study.
“Our findings emphasize how important it is to be aware of individual patient factors when prescribing a medication or developing a treatment plan for breast cancer,” said senior author Francesmarie Modugno, Ph.D.M.P.H., 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.
“It’s not one size fits all. We need to think about each patient individually to optimize outcomes and minimize risks,” said Francesmari Modugno.
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The study found that although HMT was associated with protection against developing dementia overall, this association decreased with age and also varied by race.
About two-thirds of breast cancer patients have hormone receptor-positive tumors, which grow in response to estrogen or progesterone. For these patients, HMTs can slow tumor growth by preventing hormones from binding to certain receptors. While HMT use has been linked to increased survival rates, there is conflicting evidence about whether it increases or decreases the risk of developing Alzheimer’s disease and related dementias (ADRD), which are debilitating conditions characterized by memory loss, changes in mood or behavior, and difficulties with thinking, problem-solving, and reasoning.
To improve understanding of the risk of ADRD after HMT in breast cancer patients, Modugno teamed up with lead author Chao Cai, PhD, assistant professor at the University of South Carolina College of Pharmacy. They used a federal database of people aged 65 and older to identify women who were diagnosed with breast cancer between 2007 and 2009 and who had no prior diagnosis of ADRD or a history of using HMT before their breast cancer diagnosis.
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Of the 18,808 patients who met the criteria, 66% had received HMT within three years of their diagnosis and 34% had not. During the study period of an average of 12 years of follow-up, 24% of HMT users and 28% of non-HMT users developed ADRD.
Risk of developing ADRD with HMT
To calculate the risk of developing ADRD, the researchers took into account the risk of death associated with increasing age and duration of exposure to HMTs. They found that HMT use resulted in an overall reduction in the relative risk of developing ADRD, but the protective effect of HMTs was most pronounced in patients aged 65 to 69 years and decreased with age. Notably, the risk of ADRD in HMT users was increased when patients were over the age of 80.
“Our study suggests that younger women may benefit more from HMT in terms of a reduced risk of developing Alzheimer’s disease and other types of dementia,” Cai said. “The benefits of HMT diminished for women aged 75 and older, particularly in women who are white. This suggests that the timing of HMT initiation is important and treatment plans should be tailored to the patient’s age.”
Among black women aged 65 to 74 years who used HMTs, the relative risk of developing ADRD was reduced by 24%, which decreased to 19% after age 75. Among white women aged 65 to 74 years, HMT use reduced the risk of ADRD by 11%, but this beneficial association disappeared after age 75.
“Black women have higher rates of breast cancer and have greater lifetime stress due to structural racism and other societal factors that are associated with poorer outcomes,” Modugno said. “We don’t know the mechanisms behind the racial disparities we’ve seen with risk of HMT and ADRD, but it’s possible that these factors may contribute. This needs to be investigated further.”
“These findings emphasize that when we prescribe medications or create treatment plans for breast cancer, we need to be aware of each patient’s factors,” Modugno said. “It’s not one size fits all. We need to think about each individual patient to optimize outcomes and minimize risks.”
There are three main types of HMTs: selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders. The analysis found that the risk of developing ADRD varied according to the type of HMT.
According to Cai, estrogen has neuroprotective effects, so these treatments may affect ADRD risk by mimicking estrogen, affecting estrogen production, or modulating estrogen receptor levels. HMT may also affect the clearance of a protein called beta-amyloid, the stability of tau proteins, and vascular health, all of which are closely linked to brain health and ADRD risk.
“The relationship between HMT for breast cancer and dementia risk is complex and affected by many factors,” Cai explained. “Continued research is needed to further understand the mechanisms behind this relationship and provide clear guidance on the use of HMT.”
One limitation of the study was that it only included patients over the age of 65. In the future, Cai and Modugno will also include younger women who have not yet reached menopause to further understand the relationship between HMT and dementia risk.
Other authors of the study were Kaovao Strickland, M.P.H., Sophia Knudson, Sarah Beth Tucker, and Chandana Sai Chidrala, M.S., all from the University of South Carolina.
