Associations between breast cancer and rheumatoid arthritis among older-age women in the United States.

Abstract

Background: Several studies have described an inverse association between rheumatoid arthritis (RA) and risk of breast cancer (BC), and one study reported lower risk of RA after BC. Factors contributing to this possibly bidirectional relationship remain unclear.

Methods: Using the SEER-Medicare database (2008-2021), we conducted a case-control study to evaluate the association between RA and BC risk among women aged 66-99. RA was identified from Medicare claims. We also conducted a cohort study among BC cases and controls to evaluate subsequent RA incidence. Multivariable adjusted odds ratios (ORs) were estimated using generalized linear mixed models and hazard ratios (HRs) using Cox regression.

Results: We included 204,186 BC cases and 2,897,862 controls. RA was inversely associated with BC (OR 0.80, 95%CI 0.77-0.83)-specifically, for hormone receptor positive BC (0.78, 0.76-0.81). In the cohort analysis (184,524 women with and without BC), BC was associated with lower incidence of RA (HR 0.93, 95% CI 0.88-0.98). This association did not differ by BC hormone receptor status. Instead, among women with BC, radiotherapy was associated with reduced RA incidence (HR 0.82, 95%CI 0.76-0.89). Finally, among women with hormone receptor positive BC, treatment with exemestane was associated with increased incidence of RA (HR 1.33, 95%CI 1.17-1.50).

Conclusion: These findings support a bidirectional inverse association between RA and BC. Hormone-related pathways may contribute to reduced BC risk in women with RA, whereas radiotherapy-related immune modulation may partly explain the lower incidence of RA incidence following BC. Further mechanistic studies are warranted.