In the MonarcHER phase II trial, patients with HR-positive, HER2-positive advanced breast cancer previously treated with at least two lines of anti-HER2 therapy were treated with a combination of abemaciclib with trastuzumab and fulvestrant, a selective estrogen receptor degrader (group A), abemaciclib and trastuzumab (group B), or the standard of care with trastuzumab and the physician’s choice of chemotherapy (group C). The gene discussed is ESR1; the disease is breast cancer.