Palbociclib, a novel CDK 4/6 inhibitor, was approved in February 2015 in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The gene discussed is ESR1; the disease is breast cancer.