Hormone Therapy May Reduce Dementia Risk in Patients With Breast Cancer

A study suggests hormone therapy after breast cancer may lower dementia risk, particularly for younger Black women, but further research is needed to confirm these findings.| Image Credit: Liubomyr - stock.adobe.com

Patients with hormone receptor (HR)-positive breast cancer often receive hormone-modulating therapy (HMT) treatment, but cognitive effects, including links to Alzheimer disease and related dementias (ADRDs), remain a possibility, according to a study from JAMA.¹

Oftentimes, breast cancer is diagnosed in women 50 years or older, partly because age is a considerable risk factor. Adults in this age group, typically 65 and older, are also at a higher risk of Alzheimer disease. More specifically, women 65 years or older with Alzheimer disease account for 12% of the US population. Research has found breast cancer is the second leading cause of cancer-related death in women.² Alzheimer disease is the seventh leading cause of death in the US.¹

With the rate of breast cancer survivors increasing, ADRD is a concern because this population is vulnerable, especially when over 65 years of age. While the long-term use of anti-estrogen therapies has increased survival rates among patients with breast cancer, reports of decreased cognitive function can lead to greater risk of ADRDs.

Previous research findings with reports of high doses of chemotherapy have raised concerns that cognitive impairment might become a dose-limiting treatment toxicity.³ Sometimes referred to as “chemobrain” or “chemofog”, evidence has found neurocognitive effects among patients with breast cancer who were exposed to chemotherapy. Now referred to as cancer-related cognitive impairment, it affects daily functions, work productivity, childcare, and other responsibilities among patients with a history of breast cancer.

The cohort study included women aged 65 years and older with newly diagnosed breast cancer between 2007 to 2009.¹ The National Drug Code and Healthcare Common Procedure Coding System codes defined HMT treatment into 3 different types. These included HMT as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders. Patients were followed from diagnosis until the end of 2019, offering a minimum of 10 years of follow-up. Researchers conducted the study between June 2022 to January 2024.

In the final data analysis, 18,808 women met the inclusion criteria, with 65.7% exposed to HMT following the past 3 years after diagnosis and 34.3% not exposed to HMT. Those aged 75 to 79 years were more likely to use HMT (HMT, 22% women; no HMT, 22.8%).

Both cohorts were diagnosed between the average age of 75 to 76 years and consisted mainly of White women (Black, HMT 6.6% vs non-HMT 7.1%; White, HMT 88.3% vs non-HMT 87.1%; Other, HMT 5.2% vs non-HMT 5.7%).

Over the course of 12 years of follow-up, about 23.7% HMT users and 27.9% of non-HMT users developed ADRDs. Overall, HMT was linked to a 7% lower relative risk of ADRDs (HR, 0.93; 95% CI, 0.88-0.98; P = .005).

The association between HMT treatment and the development of ADRDs decreased with age in those aged 65 to 69 years (HR, 0.48; 95% CI, 0.43-0.53).

Additionally, race was a confounding variable because the risk of ADRDs associated with HMT was reduced in women who identified as Black (HR, 0.78; 95% CI, 0.65-0.94).

The greatest reduction in ADRDs was among women aged 65 to 74 years who self-identified as Black (HR, 0.76; 95% CI, 0.62-0.92). This population also saw a greater reduction in women 75 years and older (HR, 0.81; 95% CI, 0.67-0.98).

Women who self-identified as White, aged 65 to 74 years, had an 11% relative risk reduction (HR, 0.89; 95% CI, 0.81-0.97). These associations decreased for women aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02).

No significant association between HMT and ADRDs was detected among other races. Links between age and race varied by the HMT type.

The study focused on a broad Medicare population, limiting generalizability. It lacked key genetic and protein data and details on HMT formulations and duration. Additionally, no information on drug interactions was available.

While the data provided valuable insights into HMT and ADRDs in patients with breast cancer, further research is needed to validate these findings in broader populations and understand the underlying mechanisms.

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. Key statistics for breast cancer. American Cancer Society. January 17, 2024. Accessed July 16, 2024. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html#:~:text=Breast%20cancer%20is%20the%20second

3. Van Dyk K, Ganz PA. Cancer-related cognitive impairment in patients with a history of breast cancer. JAMA. 2021;326(17):1736–1737. doi:10.1001/jama.2021.13309