Role of and in the prognosis and tamoxifen resistance of estrogen receptor-positive breast cancer.

Despite the discovery of a number of different mechanisms underlying tamoxifen resistance, its molecular pathway is not completely clear. The upregulation of and has been reported in breast cancer. Nevertheless, their role in tamoxifen resistance has not been investigated. In the present study, we compared and expression in 72 tamoxifen sensitive (TAMS) and tamoxifen-resistant (TAMR) patients. Afterward, the correlation of expression data with clinicopathological features and survival of patients was studied. Results showed that both and were significantly upregulated in TAMR compared to TAMS patients. Besides, there was a positive association between and expression. Furthermore, we evaluated their correlation with the expression of , and stemness markers. The results demonstrated that in most tissue samples there was a positive correlation between and expression with these stemness markers. Besides, the overexpression of and significantly correlated with the N stage. Moreover, the overexpression of was associated with extracapsular invasion and lymphatic invasion. High level expressions of and had a significant association with worse disease-free survival (DFS) rates. In addition, increased level of expression provides a superior predictor factor for DFS. The multivariate Cox regression analysis also revealed that for DFS, perineural invasion (PNI) was independently an unfavorable prognostic value. These findings suggest that the high expression of and could contribute to tamoxifen resistance and worse survival rates in tamoxifen-treated ER breast cancer patients.