It has additionally been demonstrated that there is an estrogen dependent downregulation of EPAS1 in ER+ but not ER- HBC and proposed EPAS1 as a negative prognostic marker in HER2+ invasive breast cancer, since overexpression of EPAS1 worsen the prognosis in HER2 and ER+ [50,51]. This evidence concerns the gene ERBB2 and invasive breast carcinoma.