In this study, we exploit two signaling pathways frequently hyperactivated in breast cancer, truncated glioma-associated oncogene homolog 1 (tGLI1) and interleukin-6/interleukin-6 receptor/glycoprotein 130 (IL-6/IL-6R/GP130) signaling, to directly target HER2-enriched breast cancer and TNBC. This evidence concerns the gene IL6R and breast carcinoma.