Cyclin-dependent kinase inhibitors (CDK4/6 inhibitors; e.g. palbociclib) are approved for use in the setting of ER+ metastatic breast carcinoma and prolong survival in combination with fulvestrant [129] and there is a current open-label phase II trial (PELOPS; NCT02764541) investigating the effect of neoadjuvant palbociclib in combination with endocrine therapy in hormone receptor positive early stage breast cancer [130]. The gene discussed is ESR1; the disease is breast cancer.