Recently, a combination of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6)—palbociclib, ribociclib, and abemaciclib—with aromatase inhibitors or the ER inhibitor fulvestrant resulted in a markedly improved progression-free survival (PFS) compared to endocrine therapy alone in patients with advanced ER+ breast cancer [5]. The gene discussed is ESR1; the disease is breast cancer.