The presence or absence of these three protein receptors are the primary defining characteristics of the four major breast cancer subtypes, listed here in increasing order of aggressiveness: luminal A (ERα+, PR+/-, HER2-), luminal B (ERα+, PR+/-, HER2+/-), HER2-overexpressing (ERα+/-, PR+/-, HER2+), and triple-negative (ERα-, PR-, HER2-) [10]. This evidence concerns the gene ESR1 and breast cancer.