Breast Cancer Hormone-Modulating Therapy May Lower Risk for Dementia

Age and racial differences in subgroup analyses emphasize the need for strategies addressing Alzheimer’s/dementia risk factors and prevention of breast cancer.

Hormone modulating therapy (HMT) used to treat patients with breast cancer was associated with a 7% reduction of developing Alzheimer’s disease and related dementias (ADRD) later in life, according to a study published in JAMA Network Open.¹ Additionally, demographic differences in subgroup analyses emphasize the need for race- and age-specific strategies addressing ADRD risk factors and prevention for patients with breast cancer, specifically for older women.

Among breast cancer survivors 65 and older during a 12-year follow-up, 23.7% of HMT users and 27.9% of non-HMT users developed ADRD (HR, 0.93; 95% CI, 0.88-0.98; P = .005). Additionally, Black-identifying women aged 65 to 74 experienced the greatest ADRD risk reduction (HR, 0.76; 95% CI, 0.62-0.92). Conversely, the association between HMT and ADRD risk reduction disappeared for White-identifying women 75 years or older (HR, 0.96; 95% CI, 0.90-1.02), despite ages 65 to 74 associated with an 11% reduction (HR, 0.89; 95% CI, 0.81-0.97).

“Our findings emphasize the importance of being cognizant of individual patient factors when we prescribe medications or develop treatment plans for breast cancer,” lead author Francesmary Modugno, PhD, MPH, professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh and member of Magee-Womens Research Institute and University of Pittsburgh Medical School Hillman Cancer Center, said in a press release on the study findings.² “It’s not one-size-fits-all. We need to think about each individual patient to optimize outcomes and minimize risks.”

Patients 65 years or older with newly diagnosed breast cancer were selected for inclusion in the study population from the SEER-Medicare linked database from 2007 to 2009. Overall, 18,808 women were included in the final data analysis, 65.7% of which had HMT exposure before 3 years of diagnosis and the remaining 34.3% did not. Additionally, the 75 to 79 years group was the most common age group in both HMT use groups, including 2721 HMT patients (22.0%) and 1469 non-HMT patients (22.8%).

Within the HMT cohort, 10,904 women self-identified as White (88.3%), 809 self-identified as Black (6.6%), and 643 identified as other (5.2%). The non-HMT group was similarly distributed, with 5622 women identifying as White (87.1%), 457 identifying as Black (7.1%), and 373 identified as other (5.7%). The mean age for each cohort was 75 years and 76 years for the HMT and non-HMT groups, respectively.

The mean time to start (TTS) HMT was 5.6 months from diagnosis (range, 0-36 months). Within 3 years following diagnosis, the mean HMT duration was 24 months (range, 0-36 months).

During the follow-up period 5038 women died, including 3262 (26.4%) of the HMT groups vs 1776 in the non-HMT group (27.5%). A statistically significant relative reduction in ADRD risk was associated with HMT use (HR, 0.93; 95% CI, 0.88-0.98; P = .005).

Reduced risk was the most pronounced in the 65-to-69-year cohort (HR, 0.48; 95% CI, 0.43-0.53; P <.001), and ADRD risk increased with HMT use at age 80 and older (HR, 1.40; 95% CI, 1.29-1.53; P <.001). Additionally, greater reductions in ADRD risk with HMT use were observed in patients who self-identified as Black (HR, 0.78; 95% CI, 0.65-0.94; P < .001) than White (HR, 0.94; 95% CI, 0.89-0.99; P <.001) or other (HR, 0.93; 95% CI, 0.72-1.18; P <.001).

Black women 75 years or older saw a reduced risk of ADRD associated with HMT use less pronounced than those aged 65 to 74 (HR, 0.81; 95% CI, 0.67-0.98). Women of other races did not see a significant change in ADRD risk in HMT use.

“While our results contribute valuable insights into the association of HMT with ADRD 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,” Modugno and study coauthors concluded.

References

1. Cai C, Strickland K, Knudsen S, Tucker SB, Chidrala CS, Modugno F. 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
2. Hormone therapy for breast cancer linked with lower dementia risk. News release. University of Pittsburgh Medical Center. July 16, 2024. Accessed July 25, 2024. https://tinyurl.com/4myvw3u7