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A new study links hormone-modulating therapy to decreased Alzheimer’s risk. Reza Estakhrian/Getty Images
  • Breast cancer affected by hormones is often treated with hormone-modulating therapy (HMT).
  • Over the years, there have been conflicting research findings on whether or not HMT may raise or lower a person’s risk of developing Alzheimer’s disease and other types of dementia.
  • A recently published study indicates that HMT is associated with a 7% lower risk of developing Alzheimer’s disease and related dementias later in life.

Between 70-80% of new breast cancer diagnoses are hormone receptor-positive. This means their tumor’s cells have proteins that bind to a specific hormone — estrogen, progesterone, or both.

Breast cancer affected by hormones is often treated with hormone-modulating therapy (HMT) before or after surgery.

There are three main types of HMT — one that blocks estrogen from linking to cancer cells, one that binds itself to the receptors on the tumor and breaks them down, and one that lowers or stops estrogen production in the body.

Over the years, there have been conflicting research findings on HMT. Some have found that it lowers a woman’s risk of developing Alzheimer’s disease and other types of dementia. Others have found that it has adverse effects on cognition.

Now, a new study published in the journal JAMA Network Open reports that HMT is associated with a 7% lower risk of developing Alzheimer’s disease and related dementias later in life.

For this study, researchers used a federal database from the National Cancer Institute to identify almost 19,000 women ages 65 and older who had been diagnosed with breast cancer between 2007 and 2009. All selected participants did not have a previous diagnosis of Alzheimer’s disease and related dementias, as well as had not used HMT before their breast cancer diagnosis.

“Our study aimed to understand the relationship between hormone modulating therapy for treating breast cancer and subsequent risk of Alzheimer’s disease and related dementias because estrogens have been associated with Alzheimer’s disease and related dementias in women,” Francesmary Modugno, PhD, MPH, professor of obstetrics, gynecology, and reproductive sciences at the University of Pittsburgh, member of Magee-Womens Research Institute and UPMC Hillman Cancer Center, and senior author of this study explained to Medical News Today.

Of the almost 19,000 female participants, 66% received HMT within three years of their breast cancer diagnosis while the remaining 34% did not.

During an average follow-up period of 12 years, researchers found that 24% of participants given HMT and 28% of non-HMT receiving participants developed Alzheimer’s disease and related dementias.

In general, scientists found women aged 65 years and older with breast cancer who received HMT had a 7% risk reduction in developing Alzheimer’s disease and related dementias overall.

In addition to the overall findings, the researchers also found some differences when looking at age ranges and ethnic groups.

For example, scientists discovered that the dementia-protective effect of HMT was most pronounced in study participants between the ages of 65 and 69. HMT’s safeguarding effect diminished as participants aged, most notably over the age of 80 where there was an increased risk of Alzheimer’s disease and related dementias in those receiving HMT.

When looking at racial differences, scientists found Black women ages 65 to 74 receiving HMT had a 24% reduction in their relative risk of developing Alzheimer’s disease and related dementias, which dropped to 19% after age 75.

Comparatively, white women ages 65 to 74 receiving HMT only had an 11% lowered Alzheimer’s disease and related dementias risk, and this benefit disappears after age 75.

“The study indicates that the protective effects of HMT against ADRD are more pronounced in women aged 65 to 74. This suggests that the timing of HMT initiation is crucial, and treatment plans should be tailored to the patient’s age.”
Chao Cai, PhD, assistant professor of Clinical Pharmacy and Outcomes Sciences in the College of Pharmacy at the University of South Carolina, and lead author of the study speaking to MNT.

“The study shows significant racial differences in the protective effects of HMT,” Cai continued. “This underscores the need for personalized treatment plans that take racial differences into account. When deciding on breast cancer treatment, it is essential to consider these individual factors along with the patient’s overall health, comorbidities, and personal preferences. Shared decision-making between patients and healthcare providers is crucial to develop a treatment plan that maximizes benefits and minimizes risks,” Cai said.

After reviewing this study, Verna Porter, MD, a board-certified neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute in Santa Monica, CA, told MNT her first reaction to the findings was one of cautious optimism.

“It’s promising to see evidence suggesting that HMT for breast cancer may also reduce the risk of Alzheimer’s and related dementias, especially in younger patients,” Porter added. “However, the increased risk for older patients and the variability by race highlight the need for personalized treatment plans.”

Porter said it is crucial for researchers to continue looking for new ways to lower dementia risk because Alzheimer’s and other dementias are debilitating conditions that severely impact patients’ quality of life and place a significant burden on caregivers and healthcare systems.

“With an aging population, the prevalence of these diseases is expected to rise, making it essential to find effective prevention strategies to reduce their incidence and improve overall public health,” she continued.

“As next steps (for this research), I would like to see research exploring the mechanisms behind the racial disparities observed in the study to develop targeted interventions; investigations into the specific types of HMT and their differential effects on dementia risk; long-term studies to confirm the findings and further elucidate the relationship between HMT and brain health; (and) development of guidelines for personalized HMT treatment plans considering individual patient factors like age, race, and overall health.”
— Verna Porter, MD

MNT also spoke with Wael Harb, MD, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, CA, about this study.

Harb commented that this study is highlighting an association between taking the hormone modulating therapy and developing dementia, which does not necessarily mean that the medication is lowering the risk of dementia and there may be some other reasons why we’re seeing this correlation.

For example, he said that study participants who received hormonal modulating therapy have tumors that are estrogen receptor-positive, which means that these are not the same type of tumors that do not receive hormone therapy.

“Patients who did not have hormone receptor-positive (breast cancer) are likely to receive more aggressive chemotherapy,” Harb explained. “We know that sometimes this patient might develop ‘chemo brain’ and if they have underlying susceptibility (to) develop dementia or related disorders, they might have accelerated the process.”

In regards to further research, Harb said he would like to see this applied to the different types of HMT used to see if there are any differences.

“I don’t think we have a good understanding of the biology (of) why these drugs would decrease (dementia risk) — we need to see some scientific rationale for how this drug would decrease cognitive decline,” he continued. “ I would like to look more carefully (at these patients) to see what chemotherapy they received — did they receive more chemotherapy, did they notice (a) decline in their cognitive ability after chemotherapy, what we call chemo brain?” Harb continued.

“[The study is] definitely intriguing and interesting, but I don’t think it’s conclusive to say that HMT decreases (the) risk of dementia. I think that’s something we need to look into further.”
— Wael Harb, MD