The phase II acelERA Breast Cancer Study evaluated ER+ HER2− relapsed breast cancer patients progressing after 1–2 lines of systemic therapy, including ET for at least 6 months and a targeted agent; one previous line of chemotherapy and fulvestrant were allowed; patients were randomly allocated to giredestrant or fulvestrant/AI (the physician’s choice of hormone monotherapy, PCET) until disease progression/unacceptable toxicity. This evidence concerns the gene ESR1 and breast cancer.