Our results suggest that a transcriptional program orchestrated by p63 and TCF7 is required for a normal differentiated myoepithelial cell phenotype and perturbations of this may contribute to the increased breast cancer risk of BRCA mutation carriers, and it may lead to the loss of myoepithelial cells in DCIS promoting progression to invasion. Here, TCF7 is linked to ductal breast carcinoma in situ.