Association Between Hormone-Modulating Breast Cancer Therapies and Incidence of Neurodegenerative Outcomes for Women With Breast Cancer

Abstract

Importance: The association between exposure to hormone-modulating therapy (HMT) as breast cancer treatment and neurodegenerative disease (NDD) is unclear.

Objective: To determine whether HMT exposure is associated with the risk of NDD in women with breast cancer.

Design, setting, and participants: This retrospective cohort study used the Humana claims data set from January 1, 2007, to March 31, 2017. The Humana data set contains claims from private-payer and Medicare insurance data sets from across the United States with a population primarily residing in the Southeast. Patient claims records were surveyed for a diagnosis of NDD starting 1 year after breast cancer diagnosis for the duration of enrollment in the claims database. Participants were 57 843 women aged 45 years or older with a diagnosis of breast cancer. Patients were required to be actively enrolled in Humana claims records for 6 months prior to and at least 3 years after the diagnosis of breast cancer. The analyses were conducted between January 1 and 15, 2020.

Exposure: Hormone-modulating therapy (selective estrogen receptor modulators, estrogen receptor antagonists, and aromatase inhibitors).

Main outcomes and measures: Patients receiving HMT for breast cancer treatment were identified. Survival analysis was used to determine the association between HMT exposure and diagnosis of NDD. A propensity score approach was used to minimize measured and unmeasured selection bias.

Results: Of the 326 485 women with breast cancer in the Humana data set between 2007 and 2017, 57 843 met the study criteria. Of these, 18 126 (31.3%; mean [SD] age, 76.2 [7.0] years) received HMT, whereas 39 717 (68.7%; mean [SD] age, 76.8 [7.0] years) did not receive HMT. Mean (SD) follow-up was 5.5 (1.8) years. In the propensity score-matched population, exposure to HMT was associated with a decrease in the number of women who received a diagnosis of NDD (2229 of 17 878 [12.5%] vs 2559 of 17 878 [14.3%]; relative risk, 0.89; 95% CI, 0.84-0.93; P < .001), Alzheimer disease (877 of 17 878 [4.9%] vs 1068 of 17 878 [6.0%]; relative risk, 0.82; 95% CI, 0.75-0.90; P < .001), and dementia (1862 of 17 878 [10.4%] vs 2116 of 17 878 [11.8%]; relative risk, 0.88; 95% CI, 0.83-0.93; P < .001). The number needed to treat was 62.51 for all NDDs, 93.61 for Alzheimer disease, and 69.56 for dementia.

Conclusions and relevance: Among patients with breast cancer, tamoxifen and steroidal aromatase inhibitors were associated with a decrease in the number who received a diagnosis of NDD, specifically Alzheimer disease and dementia.

Figure 1.. Study Design and Patient Breakdown

HMT indicates hormone-modulating therapy; NDD, neurodegenerative disease.

Figure 2.. Age-Dependent Reduction in Risk for All Neurodegenerative Diseases (NDDs) and Alzheimer Disease (AD) Associated With Hormone-Modulating Therapy (HMT) Exposure

A significantly decreased risk of diagnosis of both overall NDDs and, more specifically, AD was observed for patients treated with HMT vs those not treated with HMT.

Figure 3.. Relative Risk (RR) of All Neurodegenerative Disease, Alzheimer Disease, and Dementia Outcomes With Aromatase Inhibitors, Raloxifene, and Tamoxifen

Tamoxifen and the aromatase inhibitors were associated with significantly reduced RRs for all neurodegenerative diseases, Alzheimer disease, dementia, and non-Alzheimer dementia in the hormone-modulating therapy treatment groups. More specifically, the steroidal aromatase inhibitor (exemestane) had a greater association than nonsteroidal aromatase inhibitors (anastrozole and letrozole) with reduced RR of neurodegenerative disease outcomes.