In 2015, palbociclib was approved for use in combination with letrozole from the treatment of ER-positive/HER2-negative advanced breast cancer as initial endocrine-based therapy in postmenopausal women and, subsequently, in 2016 in combination with fulvestrant in HER-positive/HER2-negative advanced breast cancers in progression following endocrine therapy [355]. The gene discussed is ESR1; the disease is breast carcinoma.