Systemic lupus erythematosus (SLE) is linked with an increased risk of cancers, particularly hematologic malignancies. Cancer mortality among patients with SLE in the United States (U.S.) remains unclear. Our cross-sectional study sought to measure trends in cancer mortality among patients with SLE in the last 2 decades. Cancer deaths among patients with SLE from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals were measured. We used joinpoint trend analysis to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, there were 2,481 cancer deaths with comorbid SLE. Overall, the AAMRs of cancer among patients with SLE increased from 0.71 in 1999 to 1.19 per 1,000,000 individuals 2020 with the AAPC at +1.19. Women had a higher AAMR from cancer death with comorbid SLE than men (1.39 vs. 0.29 per 1,000,000 individuals). The highest AAMR was observed among African Americans (1.23 per 1,000,000 individuals), followed by Hispanics (0.61 per 1,000,000 individuals), Whites (0.58 per 1,000,000 individuals), and Asians (0.36 per 1,000,000 individuals). Those who lived in the West region and the rural region had the highest AAMR respectively (0.69 vs. 0.70 per 1,000,000 individuals). The three most common causes of cancer deaths were lung cancer (28.70%), breast cancer (8.83%), and non-Hodgkin lymphoma (4.96%). Cancer mortality in SLE patients has risen, with higher rates among African Americans, highlighting the need for targeted interventions.

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