This work demonstrates the power of applying an integrated, multi-omics approach to patient-derived models in order to identify potential therapeutic targets, provides further evidence that FGFR fusions, while occurring at a relatively low frequency in breast cancer, can confer oncogenic addiction and result in marked therapeutic responses to corresponding targeted therapy and highlights FGFR4 as an attractive target in a subset of advanced luminal breast cancer. The gene discussed is FGFR4; the disease is breast carcinoma.