A series of clinical trials are now enrolling ER+/HER2+ patients to test the efficacy of approaches combining palbociclib and anti-HER2 therapies in breast cancer (i.e., ClinicalTrials.gov identifier: NCT02448420-PATRICIA, NCT02530424-NA-PHER2 and NCT03644186-TOUCH) either as doublets or more complex combinations with the addition of endocrine therapies. The gene discussed is ESR1; the disease is breast cancer.