Furthermore, approximately 5–10% of the most aggressive form of breast cancer, triple negative breast cancer (TNBC), is associated with NRR or PEST domain mutations in NOTCH1 and NOTCH2 [37,38], but TNBC is also associated with elevated expression of JAGGED1, NOTCH1, NOTCH3 or NOTCH4, which in turn is associated with poor clinical prognosis [39,40,41,42]; for review see [43]. This evidence concerns the gene NOTCH4 and breast cancer.