While RET is known to drive the development and progression of multiple solid tumors, therapeutic agents selectively targeting RET are relatively new, though multiple multi-kinase inhibitors have shown promise as RET inhibitors in the past; further, RET has been historically neglected as a potential therapeutic co-target in endocrine-refractory breast cancers despite mounting evidence for a key pathologic role and repeated description of a bi-directional relationship with the estrogen receptor, the principal driver of most breast tumors. Here, ESR1 is linked to breast carcinoma.