ESR1 and breast carcinoma: In breast cancer models, numerous ER target genes require PR expression (i.e., via scaffolding actions in ER/PR complexes) for optimal estrogen responsiveness in the absence of exogenously added progesterone [24], while PR can dominantly repress or modify ER actions as part of ER/PR complexes when both ligands (i.e., estrogen and progesterone agonists or antagonists) are combined [25, 26].