Specifically, ligand-induced transactivation of HER2 or other members of the epidermal growth factor receptor family in tumors with low levels of HER2 generates a gene signature strongly overlapping with that of the poor prognosis, luminal B-type of ER+ breast carcinomas, suggesting that HER-activating growth factors are significant contributors to the endocrine therapy-resistant phenotype. Here, ESR1 is linked to breast carcinoma.