Hypoxia response elements have been identified on the promoters of both ERα and ERβ28 and in breast cancer cells, it has been demonstrated that hypoxia induces ESR1 repression at the transcriptional level in a process dependent on hypoxia-inducible factor 1α.29 This is consistent with our observation that the ERα antagonist also reversed the increased PH phenotype observed in the hypoxic SERT+ mice. Here, ESR1 is linked to breast carcinoma.