In combination with the estrogen inhibitor letrozole, the CDK4/6 inhibitor palbociclib has recently been approved by the US Food and Drug Administration for treatment of estrogen receptor–positive breast cancers.22 Another CDK4/6 inhibitor, ribociclib, has demonstrated efficacy in RB wild-type23 and AR mutant prostate cancer cells.24 In two clinical trials, CDK4/6 inhibition was thought to benefit prostate cancers that express wild-type RB (ClinicalTrials.gov identifiers: NCT02059213 and NCT02555189). Here, ESR1 is linked to breast cancer.