In these cohorts, tumors with reduced PIPP and PTEN expression (Z-score threshold of <1.5 relative to all breast cancers in the cohort) and/or PTEN mutation (designated PIPP–/PTEN–) were almost exclusively hormone receptor and HER2 negative (METABRIC: ER–100%, PR–100%, HER2–100%; TCGA: ER–92%, PR–96%, HER2–94%) (Fig. 7F–H, Supplementary Fig. S6E–G) and of the basal or claudin low subtype (METABRIC: 98%) (Fig. 7I). This evidence concerns the gene ESR1 and breast cancer.