ESR1 and breast cancer: Estrogen receptor-positive (ER+) breast cancer is the most common clinical subtype of breast cancer, and afflicts over 140,000 patients each year in the US.1 Although endocrine therapy (aromatase inhibition or selective estrogen receptor modulators/selective estrogen receptor down regulators; SERMs/SERDs) is largely active against ER+ disease, many patients demonstrate or develop therapeutic resistance to endocrine therapy, which can occur through a variety of clinically established mechanisms.