At the turn of the century, the combination of low estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) expression levels was shown to identify a high risk "triple-negative" breast cancer phenotype [1,2] that occurs in 10-20% of breast cancers and indicates that the cancer cannot be effectively treated by conventional therapies [3,4]. The gene discussed is ESR1; the disease is breast cancer.