ESR1 and breast cancer: Collectively, this seems to imply that suppression of ER in ER-dependent tumors can lead to drug-resistance through activation or de-repression of HER2 signaling, while, on the contrary, suppression of HER2 in HER2 over-expressing breast cancers can result in resistance to HER2-targeted therapies through activation or de-repression of ER signaling.