Dementia Risk Reduced for Some Older Breast Cancer Patients on Hormone Therapy

Hormone therapy in older women with breast cancer was associated with a reduced risk of subsequent dementia, a retrospective study of Medicare patients suggested.

Breast cancer patients who received hormone-modulating therapy had a 7% lower risk of dementia over an average follow-up period of 12 years compared with patients who did not receive hormone therapy (HR 0.93, 95% CI 0.88-0.98, P=0.005), Chao Cai, PhD, of the University of South Carolina in Columbia, and colleagues reported in JAMA Network Open.

Reduced risk was most pronounced among breast cancer patients in the 65-to-69-year-old group (HR 0.48, 95% CI 0.43-0.53), and this association diminished with increasing age. At age 80, use of hormone therapy transitioned into a positive association with dementia risk (HR 1.40, 95% CI 1.29-1.53) and continued in that direction until age 90 and beyond.

Black breast cancer patients ages 65 to 74 who used hormone therapy had a 24% relative risk reduction (HR 0.76, 95% CI 0.62-0.92). White breast cancer patients in the same age group had an 11% relative risk reduction (HR 0.89, 95% CI 0.81-0.97).

“You can see there is a certain subgroup [that] may benefit most from a certain treatment, so when treatment is given, it’s not one-size-fits-all,” Cai told MedPage Today. “Individual factors such as patient age and race should be considered to optimize outcomes and minimize risks.”

For Black women ages 65 to 74, use of aromatase inhibitors showed a slightly stronger association (HR 0.73, 95% CI 0.59-0.91) than selective estrogen receptor modulators (HR 0.80, 95% CI 0.57-1.11), although findings for selective estrogen receptor modulators were not significant. White women ages 65 to 74 had a significant risk reduction with selective estrogen receptor modulators (HR 0.81, 95% CI 0.70-0.94).

Many breast cancers are hormone-receptor positive and are treated with hormonal therapy to block estrogen’s effect on cancer cell growth. Hormonal therapies can increase survival in breast cancer, but have also been linked to reports of decreased cognitive function, Cai and co-authors pointed out. Past studies have had mixed results, showing no connection, a protective effect, or an increased risk of dementia with hormonal therapies.

Kevin Thomas Nead, MD, of the University of Texas MD Anderson Cancer Center in Houston, who wasn’t involved in the study, told MedPage Today in an email that the authors importantly “required a long duration of follow-up to be included in the cohort, which differs from other published studies and may explain why they found a different result than prior reports.”

Still, he said that though the true relationship between the two may be complex, the mixed body of research on hormone therapy and dementia underscores the challenges of retrospective study design. “Given that we now have well-conducted retrospective studies showing that [hormone modulating therapy] may increase, decrease, or not impact dementia risk, we can be confident that we need prospective data to find the true answer,” he said.

Cai and colleagues used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, which combined cancer registry data with Medicare claims, to identify women 65 and older with newly diagnosed breast cancer from 2007 to 2009. Patients with preexisting diagnoses of dementia or who had used hormone-modulating therapy before their breast cancer diagnosis were excluded.

The researchers compared women who had hormone therapy for their cancer and women who did not, following them from diagnosis to the end of 2019 for a minimum follow-up of 10 years. Hormone therapy exposure was defined as initiating at least one type of hormone-modulating medication within 3 years of first breast cancer diagnosis, including selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders. Potential covariates included demographic, sociocultural, medical, and treatment variables.

In total, 18,808 women were included in the study, and 65.7% of them had hormone therapy. The most common age group was 75-79 years; more than 80% of women identified as white and around 7% identified as Black. Most (76.1%) initiated hormone therapy with aromatase inhibitors.

Because data was limited to a Medicare population over age 65, findings could not be generalized to a younger population. Genetic information was not available; neither were data about amyloid or tau, two markers of Alzheimer’s disease. The researchers also did not look at specific formulations or durations of hormone therapies or drug utilization in the year before cohort entry.

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