High-risk cancers comprise not only metastatic cancers, which have aggressive and variable phenotypes, but also cancers with absence of targetable biomarkers such as triple-negative breast cancer (TNBC), which lacks the expression of three cellular receptors: estrogen receptor (ER), progesterone receptor, and the Human Epidermal growth factor Receptor-type 2 (HER2). This evidence concerns the gene ESR1 and cancer.