Most haplotype blocks linked to human complex traits and disorders by genome-wide association studies (GWAS) lack protein-coding sequences and are presumed to harbor DNA regulatory variants. Many GWAS regions overlap enhancer elements and most express long noncoding RNAs (lncRNAs). We mapped long noncoding RNAs expressed from breast cancer GWAS regions and identify 876 that are linked to breast cancer risk. CRISPR-Cas13d knockdown screens identified several lncRNAs whose knockdown alter breast cancer proliferation. One of these lncRNAs, we named BRRIAR, regulates interferon signalling in estrogen receptor positive (ER+) breast cancers. BRRIAR is an estrogen induced lncRNA transcribed from an 11 kb super enhancer, restricted to ER+ breast cancers. BRRIAR independently acts in the nucleus and cytoplasm to modulate interferon signaling. Nuclear, BRRIAR modulates the activity of the super enhancer which regulates the transcription factor, BHLHE40, already implicated in interferon signaling, Cytoplasmic BRRIARbinds and acts as a primer of the pattern recognition receptor RIG-I. Delivery of In vitro transcribed BRRIAR (IVT-BRRIAR) using lipid nanoparticles (LNPs) into in ER+ cell-lines and tumors triggers an IFN response that induces apoptosis in vitro and in vivo. IVT-BRRIAR also stimulates a proinflammatory immune response in human peripheral blood mononuclear cells (PBMCs). These findings emphasize the complex regulatory mechanisms at GWAS risk regions, reveal the critical role of lncRNAs as modulators of tumor immunity and identify BRRIAR as a promising RNA-based therapeutic for ER+ breast cancer.