Because of the essential role of BRCA1 in HR mediated DSB repair, Brca1 mutant mice, and human BRCA1 mutation carriers display significantly higher tumor mutational burden (TMB) compared with BRCA1-proficient breast cancers including higher frequencies of gene mutations and extensive genomic alterations, including severe chromosomal aberrations and aneuploidy2,5,7,9,16,18,19. This evidence concerns the gene BRCA1 and breast cancer.