Clinically, benefits have been demonstrated from a single injection of progesterone administered before surgery [87], and the use of a single agent progestogen has consistently shown to be clinically beneficial either as a first-line therapy in de novo metastatic ER+ breast cancer, or in advanced disease when ER-directed endocrine agents have failed [88,89,90,91,92,93,94,95,96,97,98,99,100]. The gene discussed is ESR1; the disease is breast cancer.