ESR1 and breast cancer: It is hypothesized that IGFBP-3 expression will induce the transcription of important biomarkers for proliferation and aggression, such as Ki-67, an important proliferation biomarker whose level is tightly associated with breast cancer aggressiveness and ER/PR negativity (38); EPHA2, a biomarker associated with basal-like/triple-negative breast cancers (39), antiestrogen resistance (40), and EMT in MCF7-10A (41, 42); and MDM4 (aka MDMX), an oncogene that promotes ERα degradation by stabilizing the E3 ubiquitin ligase MDM2 (43).