— Age-Related Outcomes

A retrospective analysis involving Medicare patients suggested that hormone therapy in older women with breast cancer was linked to a lower risk of developing dementia.

The study showed that breast cancer patients who underwent hormone-modulating therapy had a 7% reduced likelihood of dementia over an average follow-up of 12 years compared with those who didn’t receive the therapy (HR 0.93, 95% CI 0.88-0.98, P=0.005), according to research led by Chao Cai, PhD, from the University of South Carolina, published in JAMA Network Open.

The reduction in dementia risk was most striking in breast cancer patients aged 65–69 (HR 0.48, 95% CI 0.43-0.53), but this benefit lessened progressively with age. By age 80, hormone therapy corresponded to an increased risk of dementia (HR 1.40, 95% CI 1.29-1.53), with this upward trend continuing into the 90s.

Among Black breast cancer patients aged 65 to 74, hormone therapy demonstrated a 24% relative reduction in dementia risk (HR 0.76, 95% CI 0.62-0.92). White patients in the same age bracket saw an 11% relative risk reduction (HR 0.89, 95% CI 0.81-0.97).

"There’s a clear pattern indicating certain subgroups may benefit more from targeted treatments. This is why a one-size-fits-all approach doesn't apply," Cai told MedPage Today. "Considering individual factors such as age and race could enhance outcomes and reduce risks."

For Black women aged 65 to 74, aromatase inhibitors showed a slightly greater benefit (HR 0.73, 95% CI 0.59-0.91) than selective estrogen receptor modulators (HR 0.80, 95% CI 0.57-1.11), though the latter findings were not statistically significant. Meanwhile, white women experienced a significant reduction in dementia risk using selective estrogen receptor modulators (HR 0.81, 95% CI 0.70-0.94).

Many breast cancers are hormone-receptor positive, and hormonal therapy is commonly used to reduce estrogen’s influence on tumor cells. Although these therapies improve breast cancer survival, they have been linked to reports of cognitive decline. As Cai and co-authors noted, previous studies have been inconsistent, with some indicating no link, while others suggesting a protective effect or even increased risk of dementia due to hormonal treatment.

Kevin Thomas Nead, MD, from the University of Texas MD Anderson Cancer Center, who was not involved in the research, told MedPage Today that the study’s unique requirement for sustained follow-up accounts for its diversion from prior studies. "Their extended duration of follow-up may provide a reason for the different results," he remarked.

Nonetheless, Nead emphasized the complexity of the association between hormone therapy and dementia, largely due to the inconsistent outcomes of retrospective studies. "Considering the evidence we now have, showing hormone-modulating therapy could raise, lower, or have no impact on dementia risk, we need future prospective studies to pinpoint the true relationship," he concluded.

Cai's team used data from the SEER-Medicare linked database—a resource combining cancer registry information with Medicare claims—to identify women aged 65 and older, newly diagnosed with breast cancer between 2007 and 2009. Women with preexisting diagnoses of dementia or those who had hormone-modulating treatment prior to cancer diagnosis were excluded from the study.

The researchers monitored patients with and without hormone therapy from the time of cancer diagnosis until the end of 2019, ensuring a minimum 10-year follow-up. Hormone therapy exposure was defined as starting at least one form of hormone-modulating medication within 3 years of the initial breast cancer diagnosis. These medications included selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders. Several demographic, medical, and treatment-related variables were also included as potential covariates.

A total of 18,808 women participated in the study, two-thirds (65.7%) of whom received hormone therapy. The most common age group was 75-79 years, with over 80% of participants identifying as white and approximately 7% as Black. The majority (76.1%) initiated hormone therapy with aromatase inhibitors.

Given that the study's scope was limited to a Medicare population aged 65 and older, the findings may not be fully applicable to younger women. Additionally, the researchers could not access genetic data or biomarkers for Alzheimer’s disease, such as amyloid or tau proteins. They also did not investigate variations in hormonal therapy formulations, durations, or drug use before the cohort's entry.

Disclosures

The study was funded by the National Institutes of Health, the Carolina Center on Alzheimer's Disease and Minority Research pilot project, and the Dean's Faculty Advancement Fund at the University of Pittsburgh.

Cai disclosed grants from the University of South Carolina.

Co-author Modugno acknowledged grants from the University of Pittsburgh.

Nead reported no conflicts of interest.

Primary Source: JAMA Network Open

Source Reference: Cai C, et al "Alzheimer’s Disease and Dementia Risk Following Hormone-Modulating Therapy in Breast Cancer Patients" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.22493.