Hormone-Modulating Therapy for Breast Cancer Appears Protective Against Dementia

Breast Cancer - Female Anatomy: © peterschreiber.media - stock.adobe.com

A recent study identified that hormone-modulating therapy (HMT) has varying protective effects on the risk of Alzheimer disease and dementia in patients with breast cancer depending on their age and race.

The study, published in JAMA, assessed data from 18,808 women aged 65 and older who were diagnosed with breast cancer between 2007 and 2009. Medicare claims data were used to verify Alzheimer disease and dementia diagnoses, and patients who were diagnosed with Alzheimer disease or dementia or who had received HMT prior to the study window were excluded.

With an average of 12 years of follow-up, 23.7% of patients who received HMT (n = 2926) and 27.9% who did not receive HMT (n = 5622) developed Alzheimer disease or dementia. This demonstrated a 7% lower relative risk of Alzheimer disease or dementia with HMT (HR, 0.93; 95% CI, 0.88-0.98; P =.005).

This reduction in risk with HMT was most strongly seen in Black patients aged 65 to 75, where there was a 24% reduced risk (HR, 0.76; 95% CI, 0.88-0.95; P =.005). Conversely, White patients aged 65 to 74 only had an 11% risk reduction with HMT (HR, 0.89; 95% CI, 0.81-0.97). Generally, the associated risk reduction was lower for patients 75 years and older (HR, 0.81; 95% CI, 0.67-0.98).

For patients of other races, there was no significant association between HMT and Alzheimer disease or dementia risk (HR, 0.96; 95% CI, 0.90-1.02).

Investigators also looked at the relative risks of aromatase inhibitors vs selective estrogen receptor modulators (SERMs). Aromatase inhibitors like anastrozole, letrozole, and exemestane (Aromasin) showed a larger effect compared with SERMs, with HRs of 0.73 and 0.80, respectively. However, investigators noted that the results for SERMs like tamoxifen (Soltamox) and raloxifene (Evista) were not significant. SERMs did appear to be slightly more protective in White patients (HR, 0.81; 95% CI, 0.70-0.94). Selective estrogen receptor degraders like fulvestrant did not return significant results (HR, 0.37; 95% CI, 0.13-1.05; P =.06).

While investigators included estrogen receptor (ER) and progesterone receptor (PR) status as covariates, they noted the need for further research to potentially connect ER/PR status to Alzheimer disease and dementia risk.

“…while our results contribute valuable insights into the association of HMT with [Alzheimer disease and dementia] in the breast cancer population, further research is warranted to validate the observed associations in diverse populations and to elucidate the mechanisms underlying our observations,” study authors wrote.

REFERENCE:

Cai C, Strickland K, Knudsen S, et al. Alzheimer disease and related dementia following hormone-modulating therapy in patients with breast cancer. JAMA Netw Open. 2024;7(7):e2422493. doi:10.1001/jamanetworkopen.2024.22493