ESR1 and breast carcinoma: Although the 5-year survival rate for breast cancer has significantly improved, in part due to the development of endocrine-based therapies [44], significant challenges to successful therapy remain, in that breast tumors exhibit heterogeneous phenotypes, including receptor-positive (ER+, PR+, HER2+), triple-negative (ER−, PR−, HER2−), and combinations of these variants.