Several ESR1 mutations have been functionally characterised and confer key attributes associated with ET resistance, indicating mechanistic roles in resistance such as estrogen independence, increased transcription of ER target genes like PGR (progesterone receptor), GREB1 (growth regulation by estrogen in breast cancer 1), and MYC (c-myc), and increased proliferation and altered ER conformation [24,25] (Figure 2). This evidence concerns the gene PGR and breast cancer.