ESR1 and breast cancer: Specifically, HER2/MAPK kinase signaling activates E2F transcription factors, leading to the transcription of CCND1 gene encoding cyclin D1, while active estrogen receptor alpha (ERα) in complex with FOXA1 transcription factor intensifies CCND1 transcription through an estradiol-responsive enhancer [85]. CCND1 gene located on chromosome 11q13 is amplified in ~15% of breast cancers [86, 87].