Alzheimer disease risk reduced by hormone therapy for breast cancer treatment

There is an association between hormone therapy use for breast cancer and protection against Alzheimer disease and related dementias (ADRD) when aged 65 years and older, according to a recent study published in JAMA Network Open.¹

Thirty-one percent of all new cancer cases in the United States are breast cancer, and 83% of invasive breast cancers are observed in women aged at least 50 years. Data has indicated a median age of 62 years during diagnosis, and a median age of 69 years at breast cancer death.²

Over time, breast cancer survival has improved, leading to over 2.5 million breast cancer survivors aged over 65 years.¹ This has increased concerns about treatment-related complications among older adults.

Alzheimer disease is reported in 10.8% of patients aged 65 years and older and is the seventh leading cause of death in the United States. The number of people with ADRD is expected to increase over time, leading to concerns about development in breast cancer survivors.

Investigators conducted a study to determine the association between hormone-modulating therapy (HMT) among breast cancer patients and ADRD risk. Demographic, sociocultural, and clinical information about breast cancer patients was obtained from the Surveillance, Epidemiology, and End Results Medicare linked database.¹

Participants included women aged at least 65 years recently diagnosed with breast cancer between 2007 and 2009. HMT types included selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and selective estrogen receptor degraders (SERDs).

ADRD was defined as the primary outcome of the analysis, reported based on International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. ADRD subtype codes were also included to account for all ADRD patients. Covariates included demographic, sociocultural, medical, and treatment variables.

There were 18,808 breast cancer patients included in the final analysis, 65.7% of whom had HMT exposure within 3 years after diagnosis and 34.3% did not have HMT exposure. Patients were most commonly aged 75 to 79 years, with a mean age at diagnosis of 75 years in the HMT group and 76 years in the non-HMT group.¹

A mean time to start HMT of 5.6 moths from diagnosis was reported, with 76.1% of HMT users initiating with AIs, 23.6% with SERMs, and only 0.3% with SERDs. HMT lasted for a mean 24 months within 3 years after breast cancer diagnosis.

ADRD was reported in 23.7% of HMT users and 27.9% of non-HMT users by the end of the follow-up period. Death was reported in 26.4% and 27.5%, respectively. This indicated a significant association between HMT use and reduced risk of ADRD, with a hazard ratio (HR) of 0.93.¹

HRs were also significant for AI and SERM separately, at 0.93 and 0.89, respectively. However, SERD was not significantly associated with reduced risk of ADRD, with an HR of 0.37.

An age-modified association between HMT and ADRD risk was identified during subgroup analyses. Patients aged 65 to 69 years had the most reduced risk with an HR of 0.48. In comparison, by the age of 80 years, HMT was positively associated with ADRD, with an HR of 1.40.

These results indicated an association between HMT use and improved protection against ADRD among breast cancer patients, with age considered an important modifier in this link. Investigators recommended further research to validate these associations in diverse populations.¹

Reference

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. GiaquintoAN, SungH, MillerKD,et al.Breast cancer statistics, 2022. CA Cancer J Clin. 2022;72(6):524-541. doi:10.3322/caac.21754