ESR1 and breast cancer: In fact, estrogen is well-known as a proliferative hormone and a driver of oncogenic and proliferative gene networks in estrogen receptor positive breast cancer, where it serves as a nuclear hormone; indeed, upon binding its receptor, it leads to the internalization of the receptor which in turn serves as a transcription factor, transitioning to the nucleus where it binds the promoters of the oncogenes that it activates (and of the tumor suppressors that it represses) [47,48].