Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important 
transcriptional activator involved in the cellular defense mechanisms against 
electrophilic and oxidative stress. Recent studies have demonstrated that the 
expression of NRF2 protein is upregulated in several human malignancies and is 
associated with worse prognosis in these patients. However, the pathological and 
clinical significance of NRF2 has remained largely unknown in breast cancer 
patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast 
carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the 
breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was 
significantly associated with histological grade, Ki-67 labeling index, p62 
immunoreactivity, and
NAD(P)H: quinone oxidoreductase 1 (NQO1) immunoreactivity, and the results of 
multivariate analyses revealed that NRF2 status was an independent adverse 
prognostic factor for both recurrence and disease-free survival of the patients. 
Subsequent in vitro studies demonstrated that the expression of NRF2 
significantly increased the proliferation activity of MCF7 and SK-BR-3 breast 
carcinoma cells. These results indicate that nuclear NRF2 protein plays 
important roles in the proliferation and/or progression of breast carcinoma, and 
nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor 
in breast cancer patients.