Key genes involved in BC with high TMB include TP53, KMT2D, KDM6A, ARID1A, KMT2C, PIK3CA, FAT4, EP300, and RB1. Additionally, some of the MMR (MSH2, MSH6), DDR (ATM, BRCA2, POLQ, CDK12, ATR, BRIP1), and polymerase-encoding genes (POLE, POLD1) are frequently altered in TMB high tumors (59, 60). This evidence concerns the gene PIK3CA and breast cancer.