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

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.