ESR1 and breast cancer: Among 1.38 million newly diagnosed breast cancer cases each year, 65% to 70% of them are estrogen receptor positive.1 Although single-agent endocrine therapy has significantly extended survival for patients with estrogen receptor–positive breast cancer, resistance to endocrine therapy is common, reported in up to 50% of patients.2 To extend treatment benefit and delay the development of endocrine therapy resistance, a combination of endocrine therapy with cytotoxic chemotherapy has been proven to be effective in up to 30% of estrogen receptor–positive breast cancers.3,4,5,6