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A recent study found that hormone-modulating therapy (HMT), commonly used to treat breast cancer, was linked to a 7% reduced likelihood of developing Alzheimer's disease and other forms of dementia in the future.
"Our findings emphasise the importance of being cognizant of individual patient factors when we prescribe medications or develop treatment plans for breast cancer," said senior author Francesmary Modugno, Ph.D. M.P.H., professor of obstetrics, gynaecology and reproductive sciences at the University of Pittsburgh and member of Magee-Womens Research Institute and UPMC Hillman Cancer Center.
"It's not one-size-fits-all. We need to think about each individual patient to optimise outcomes and minimise risks," added Francesmary Modugno.
The study found that although HMT was linked with protection against the development of dementia overall, the association decreased with age and varied by race.
The majority of breast cancer patients, around two-thirds of them, have tumours that are sensitive to hormones like estrogen and progesterone. Hormone therapy can help slow down the growth of these tumours by blocking the hormones from attaching to specific receptors. While hormone therapy has been associated with improved survival rates, there is conflicting evidence regarding its potential impact on the risk of developing Alzheimer's disease and related dementias (ADRD). These conditions are marked by memory loss, changes in mood or behaviour, and difficulties with cognitive functions such as problem-solving and reasoning.
In order to better comprehend the risk of Alzheimer's disease and related dementias (ADRD) after hormone-modifying therapy (HMT) in breast cancer patients, Modugno collaborated with Chao Cai, PhD, an assistant professor at the University of South Carolina College of Pharmacy. They analysed a national database of individuals aged 65 and above to identify females diagnosed with breast cancer between 2007 and 2009. These individuals had no prior ADRD diagnosis or history of HMT use before their breast cancer diagnosis.
Of 18,808 patients who fit the criteria, 66% had received HMT within three years of their diagnosis and 34 per cent had not. During an average of 12 years of follow-up, 24 per cent of HMT users and 28 per cent of non-HMT users developed ADRD.
The researchers considered the risk of mortality related to advancing age and length of exposure to hormone therapy (HMT) in order to determine the risk of developing Alzheimer's disease and related dementias (ADRD). They discovered that although HMT use was linked to an overall reduction in the relative risk of developing ADRD, the protective impact of HMT was most noticeable in individuals between the ages of 65 and 69 and declined as age increased. It's noteworthy that among patients over 80 years old, HMT users faced an elevated risk of ADRD.
"Our study suggests that younger women may benefit more from HMT in terms of reduced risk of developing Alzheimer's disease and other types of dementia," said Cai. "The benefits of HMT decreased for women aged 75 and older, particularly in those who identified as white. This suggests that the timing of HMT initiation is crucial and treatment plans should be tailored to a patient's age."
Black women aged 65 through 74 who used HMT had a 24% reduction in relative risk of developing ADRD, which dropped to 19% after age 75. White women aged 65 through 74 had an 11% reduction in risk of ADRD with HMT use, but this beneficial association disappeared after age 75.
"Black women have higher rates of breast cancer and tend to have higher lifetime stress due to structural racism and other societal factors, which are associated with worse outcomes," said Modugno. "We don't know the mechanisms behind the racial disparities we saw with HMT and risk of ADRD, but it's possible that these factors could contribute. It deserves further investigation."
"These findings emphasise the importance of being cognizant of individual patient factors when we prescribe medications or develop treatment plans for breast cancer," Modugno said. "It's not one-size-fits-all. We need to think about each individual patient to optimise outcomes and minimise risks."
There are three main types of HMT: selective estrogen receptor modulators, aromatase inhibitors and selective estrogen receptor degraders. The analysis found that risk of developing ADRD varied by HMT type.
According to Cai, estrogen may have protective effects on the brain, so these treatments could potentially impact the risk of Alzheimer's disease and related dementias by imitating estrogen, influencing its production, or adjusting estrogen receptor levels. HMT could also impact the removal of beta-amyloid protein, the stability of tau protein, and vascular health, all of which are closely associated with brain function and the risk of Alzheimer's disease and related dementias.
"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 the mechanisms behind this association and provide clearer guidance on the use of HMT."
A limitation of the study was that it only included patients over 65. In the future, Cai and Modugno will include younger women who haven't reached menopause yet to further understand the link between HMT and dementia risk.
Other authors on the study were Kaowao Strickland, M.P.H., Sophia Knudsen, Sarah Beth Tucker, and Chandana Sai Chidrala, M.S., all of the University of South Carolina.
(with ANI inputs)
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