In the presence of persistent HRG-induced activation of HER2:HER3 signaling, the resulting augmentation of IL-8 secretion will further potentiate the non-genomic (e.g., MAPK- and PI3K-driven) potentiation of the unliganded transcriptional activity of ERα (e.g., via transactivation of HER2 [58,59]) characteristic of the endocrine-resistant phenotype in HRG-overexpressing ER+ breast cancer cells. The gene discussed is ESR1; the disease is breast carcinoma.