Association of systemic lupus erythematosus autoantibody diversity with breast cancer protection

BACKGROUND: Epidemiologic data suggest that patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer than women in the general population. In light of mechanistic studies suggesting that anti-DNA antibodies have anti-cancer effects, we sought to examine breast cancer risk in autoantibody strata in a well-characterized SLE cohort. METHODS: SLE patients without a cancer diagnosis prior to entry in the Hopkins Lupus Cohort were studied (N = 2431). Overall and site-specific cancer incidence was calculated in racial strata and compared with the US Surveillance, Epidemiology and End Results (SEER) registry. Breast cancer incidence was further examined in autoantibody subsets. Patients were considered positive for an autoantibody if they were ever positive for a specificity during their disease course. RESULTS: Patients with SLE had a 37% lower risk of breast cancer (SIR 0.63, 95% CI 0.39–0.95). The risk of HPV-associated cancers (SIR 4.39, 95% CI 2.87–6.44) and thyroid cancer (SIR 2.27, 95% CI 1.04–4.30) was increased. Cancer risk varied by race, with breast cancer protection occurring in non-African Americans (SIR 0.29, 95% CI 0.11–0.63) and the increased risk of HPV-associated cancers occurring in African Americans (SIR 7.23, 95% CI 4.35–11.3). Breast cancer risk was decreased in patients ever positive for anti-dsDNA (SIR 0.55, 95% CI 0.29–0.96), anti-La (SIR 0.00, 95% CI 0.00–0.78), and lupus anticoagulant (SIR 0.37, 95% CI 0.10–0.94). Patients who were positive for fewer (0–2) SLE autoantibodies did not have a lower risk of breast cancer (SIR 0.84, 95% CI 0.47–1.39), but patients with 3+ autoantibodies had a 59% decreased risk (SIR 0.41, 95% CI 0.16–0.84). CONCLUSIONS: Positivity for multiple SLE autoantibodies was associated with a lower risk of breast cancer, supporting the hypothesis that a highly diversified immune response may exert an anti-cancer effect against some cancers. Validation of racial differences in cancer risk in SLE is required to determine whether cancer screening strategies should be targeted to racial subgroups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-021-02449-3.