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Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multi-organ involvement, and some studies have found that SLE has a reduced risk of breast cancer (BRCA). So, we tried to find prognostic genes for BRCA related to SLE by integrated analysis and machine learning. First, we downloaded 2 SLE datasets from Gene Expression Omnibus (GEO) and BRCA data from the Cancer Genome Atlas (TCGA). Subsequently, we performed differentially expressed genes (DEGs) and functional enrichment analysis by Metascape in SLE. Genes that were differentially expressed in both datasets were the validated DEGs. And after constructing PPI network, genes with nodes >30 were intersected with survival genes in BRCA to obtain candidate genes. Then, the candidate genes were validated by lasso regression in both training and validation sets to obtain prognostic genes. Afterwards, we investigated the diagnostic potential of prognostic genes for SLE and the predictive efficacy for BRCA prognosis. Moreover, GSEA analysis and immune infiltration were performed for SLE and BRCA. Finally, we constructed a prognostic gene-miRNAs network and did functional enrichment of the shared genes. DEGs for SLE were mainly enriched with neutrophil degranulation and IFN pathways. After the lasso model of BRCA was established, IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE and had good predictive ability for the prognosis of BRCA. Prognostic genes had excellent diagnostic potential for SLE, with IFI35 and EIF2AK2 positively associated with SLE activity and IRF7 positively associated with IFI35. GSEA showed that both SLE and BRCA were associated with ubiquitinated degradation. Immune infiltrates suggest that plasma cells, dendritic cells (DC), neutrophils and monocyte were elevated in SLE. DC, NK and CD8+ T cells were elevated in the BRCA low-risk group. Finally, 5 shared miRNAs were confirmed, which were mainly enriched in the IFN pathway. IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE. IFN pathway played an important role in the etiology of SLE and the prognosis of BRCA. [ABSTRACT FROM AUTHOR]