What Is the Relationship Between Hormone-Modulating Therapies and Incidence of Neurodegenerative Diseases?

Two hormone-modulating breast cancer therapies (HMTs), tamoxifen and steroidal aromatase inhibitors, were associated with a decrease in the number of women who received a diagnosis of a neurodegenerative disease (NDD), according to a study published in JAMA Network Open. Specifically, the 2 HMTs were associated with significant decreases in diagnoses of Alzheimer disease (AD) and dementia.

The retrospective cohort study included Humana claims data filed between January 2007 and March 2017. In total, data from 57,843 women 45 years and older with a diagnosis of breast cancer were included in the study. Patient claims records from private payers and Medicare were analyzed to determine if diagnoses of NDD were made within 1 year after breast cancer diagnosis throughout the duration of enrollment in the claims database.

HMTs were defined as selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors.

Behind skin cancer, breast cancer is the second most common cancer in women worldwide, with around 12.8% of women being diagnosed with the disease in their lifetime. “With the increased life expectancy seen after treatment, therapy selection for breast cancer should include a careful discussion of the risks and benefits of each treatment option that may be associated with a reduced risk of neurodegenerative disease,” researchers said.

As women are more likely than men to develop AD, researchers also screened for diagnoses of multiple sclerosis (MS), Parkinson disease, and amyotrophic lateral sclerosis. However, “AD affects 1 in 9 persons in the US older than 65 years, two-thirds of whom are women,” researchers note.

The analyses of unadjusted population data found that HMT exposure, compared with no HMT exposure, was associated with a significant decrease in incidence for the following NDDs:

• AD (900 of 18,126 [5.0%] vs 2436 of 39,717 [6.1%]; P <.001)
• Dementia (1894 of 18,126 [10.4%] vs 4892 of 39,717 [12.3%]; P <.001)
• Non-AD dementia (1079 of 18 126 [6.0%] vs 2657 of 39,717 [6.7%]; P <.001)
• All NDDs (2272 of 18,126 [12.5%] vs 5770 of 39,717 [14.5%]; P <.001)

Researchers also found that “the outcomes of MS and Parkinson disease were not significantly different among those with HMT exposure. Although not significant, the incidence of amyotrophic lateral sclerosis appeared to be increased among patients exposed to HMT.”

Patients who received HMT were further categorized into 3 groups based on the HMT: tamoxifen (5335), raloxifene (1972), or aromatase inhibitors (16,032). Patients treated with tamoxifen showed the “strongest associated decreased risk for each disease,” while those who received aromatase inhibitors saw a reduction in the relative risk for the development of NDDs.

Researchers point out the study shows the beneficial effects of exposure to HMT as a prophylactic treatment for the potential prevention of AD.

“As we advance in our abilities to prevent, treat, and cure cancer, discussions around optimal care will need to include understanding the long-term outcomes of therapy selection for age-related NDDs,” the authors conclude. “The fact that…women are disproportionately affected by AD and related dementia provides us with an opportunity to reduce the global disease burden of NDDs.”

Reference

Branigan GL, Soto M, Neumayer L, et al. Association between hormone-modulating breast cancer therapies and incidence of neurodegenerative outcomes for women with breast cancer [published online March 24, 2020]. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2020.1541.