Moreover, the described correlation between lower cytoplasmic staining of NOTCH-1 protein and adverse outcomes, such as cancer recurrence, bone metastasis, and worse disease-free survival, particularly in patients with estrogen receptor-positive ER/HER2+ cancers, has been reported, thus adding valuable context to the potential significance of NOTCH-1 in breast cancer [42]. This evidence concerns the gene ESR1 and cancer.