Notch1 in Tumor Microvascular Endothelial Cells and Tumoral miR-34a as Prognostic Markers in Locally Advanced Triple-Negative Breast Cancer

PURPOSE: Triple-negative breast cancer (TNBC) is associated with poor prognosis with limited treatment options. Angiogenesis is known to be involved in the progression of TNBC, and targeting this pathway results in modest clinical benefits. In this study, we analyzed the role of tumor microvascular endothelial Notch1 (EC Notch1) and tumoral miR-34a as prognostic markers in patients with TNBC. METHODS: The expression of miR-34a was analyzed using archival tumor tissues from 114 patients with TNBC. Simultaneously, archival tumor tissues were also checked for the expression of CD34 and Notch1 by immunostaining. The ratio of Notch1-microvascular density (MVD) to CD34-MVD was defined as EC Notch1. The association between the expression of miR-34a or EC Notch1 and clinicopathological characteristics was analyzed. RESULTS: In the overall patient population, patients with low expression of EC Notch1 was associated with better overall survival (OS, p = 0.041) than those with high expression of EC Notch1. In lymph node-positive TNBC patients, high levels of miR-34a and low levels of EC Notch1 correlated significantly with higher survival benefits in terms of OS (p = 0.026), disease-free survival (p = 0.009), and metastasis-free survival (p = 0.038) relative to that in other patients. Decreased expression of EC Notch1 and increased expression of miR-34a also showed a survival benefit in locally advanced TNBC. CONCLUSION: The fact that miR-34a and EC Notch1 are associated with the angiogenesis suggests that angiogenesis may play a role in the development and progression of TNBC.