The association between Notch4 expression, and clinicopathological characteristics and clinical outcomes in patients with breast cancer.

Notch4, a family member of the Notch signaling pathway, has important roles in cellular developmental pathways, including proliferation, differentiation and apoptosis. The present study aimed to investigate the association between Notch4 expression and clinical outcomes with immunohistochemistry. Notch4 was expressed in 55.6% of triple-negative breast cancer (TNBC), 45.8% of Her-2-overexpressing and 25.5% of luminal breast cancer cases, with significantly higher expression occurring in TNBC (P<0.05). Furthermore, Notch4 expression was inversely associated with estrogen receptor (ER) and/or progesterone receptor positivity, and positively associated with larger tumor size, more lymph node involvement, and more advanced tumor node metastasis stage (P<0.05). No significant association was identified regarding age, menopausal status, Her-2 status or distant metastasis. Univariate survival analysis revealed that patients with low Notch4-expressing tumors exhibited a lower relative risk of cancer recurrence compared with patients with high Notch4-expressing tumors. However, in the luminal cohort, high Notch4 expression conferred significantly lower 5-year overall survival (OS) rates compared with Notch4 low-expression groups (P=0.003) but not in TNBC and Her-2-overexpressing patients. In conclusion, Notch4 expression was significantly higher in patients with TNBC and Her-2-overexpressing breast cancer compared with luminal breast cancer patients. Notch4 expression is associated with aggressive clinicopathological and biological phenotypes, and may predict poor prognosis in luminal breast cancer patients.