We have not only demonstrated a direct relationship between HER2 overexpression and HIF-2α in breast cancer cell lines and patient gene expression data, but have shown both an increased sensitivity of HER2-positive cell lines to HIF-2-specific inhibition and demonstrated the ability of HIF-2α- or HIF-2-specific target genes to act as prognostic indicators for disease-specific survival in HER2-positive breast cancers. The gene discussed is EPAS1; the disease is breast cancer.