Abstract
BackgroundEpidemiologic 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.MethodsSLE 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.ResultsPatients 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).ConclusionsPositivity 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.
Highlights
Data from several systemic inflammatory rheumatic diseases suggest that distinct immune responses may be markers of increased cancer risk [1]
Intriguing new data demonstrate that scleroderma patients with anti-centromere antibodies have a lower risk of cancer than that expected in the general population and that scleroderma patients with autoantibodies against both RNA polymerase III (POLR3) and the large subunit of RNA polymerase I (RPA194) have a lower frequency of cancer than those with anti-POLR3 alone [3, 6]
Study population Patients seen at the Johns Hopkins Lupus Center for their first visit between 1987 and 2018 were eligible for the study if they consented to participate in the Institutional Review Board (IRB)-approved cohort database and had a diagnosis of systemic lupus erythematosus (SLE) by revised American College of Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria [13, 14]
Summary
Data from several systemic inflammatory rheumatic diseases suggest that distinct immune responses may be markers of increased cancer risk [1]. Intriguing new data demonstrate that scleroderma patients with anti-centromere antibodies have a lower risk of cancer than that expected in the general population and that scleroderma patients with autoantibodies against both POLR3 and the large subunit of RNA polymerase I (RPA194) have a lower frequency of cancer than those with anti-POLR3 alone [3, 6] These findings suggest that multiple, orthogonal immune responses targeting linked molecular machinery may confer cancer protection. Anti-DNA antibodies were found to be lethal to BRCA2-deficient human cancer cells [11], suggesting that the presence of lupus autoantibodies may contribute to the decreased risk of breast cancer observed in SLE patients It remains unknown whether breast cancer risk in SLE patients varies by autoantibody subtype or with increased diversity of the immune response. 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 wellcharacterized SLE cohort
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
