In addition, clinical evidence presented here of co-expression of receptors initiating TGFβ and E2 signaling at higher levels in clinical breast cancer BMETs (vs. primary tumors) is also consistent with a key role of TGFβ signaling within the bone microenvironment for ER+ tumors, and with other clinical datasets associating TGFβRII expression with ER+ tumors [59]. Here, ESR1 is linked to breast cancer.