SPEN and breast cancer: By examining the differentially mutated genes, three were of particular interest in breast cancer: (i) the ESR-1 gene was significantly more frequently mutated in HER2-negative tumors, (ii) TP53 mutations were significantly more frequent in HER2-positive tumors, and (iii) the SPEN gene was more frequently mutated in HLBCs, in comparison with both HER2-negative and HER2-positive carcinomas.