The monarcHER trial (NCT02675231), a phase 2 multi-center trial, aimed to compare the efficacy of the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor abemaciclib plus the HER2 targeting antibody trastuzumab with or without the estrogen receptor antagonist fulvestrant to standard chemotherapy plus trastuzumab in women with advanced breast cancer [72]. The gene discussed is ESR1; the disease is breast cancer.