Nrf2 Expression Level and Estrogen Function in Brca1-Mutated Breast Cancer Publisher Pubmed



Derismahafi Z ; Farhud D ; Razavirad A ; Muhammadnejad A ; Jahanbin B ; Farivar S ; Shirkoohi R
Source: BMC Cancer Published:2025

Abstract

Background: Breast cancer (BC) is the most common malignancy diagnosed in women, with approximately 5–10% of cases attributed to hereditary factors. Although the tumor suppressor breast cancer susceptibility gene 1(BRCA1) is ubiquitously expressed, it is not clear why BRCA1 mutations overwhelmingly predispose to breast and ovarian cancers. Estrogen has been proposed to promote the survival of BRCA1-deficient cells under oxidative stress by activating nuclear factor erythroid-2-related factor 2 (NRF2), potentially driving malignant transformation. This study investigates the role of estrogen and NRF2 expression in BRCA1-mutated breast cancer. Methods: We analyzed 70 formalin-fixed, paraffin-embedded (FFPE) tissue samples (tumor and adjacent non-tumoral) from 15 BRCA1-mutated breast cancer patients and 20 non-mutated controls. Both adjacent non-tumoral and tumoral breast tissue were paired samples from the same patient for the two groups. NRF2 expression was quantified using qRT-PCR, while estrogen activity was indirectly assessed via immunohistochemical (IHC) analysis of focal adhesion kinase (FAK) protein expression. Results: NRF2 was significantly overexpressed in BRCA1-mutated tumors compared to controls (p = 0.036). In contrast, no significant difference in estrogen-mediated FAK expression was observed between BRCA1-mutated and control tumors. Conclusions: Our findings indicate that NRF2 upregulation is a distinguishing feature of BRCA1-mutated breast cancer, suggesting its potential involvement in tumorigenesis. These results offer new paths into targeted prevention and therapeutic strategies for BRCA1-mutation carriers. © 2025 Elsevier B.V., All rights reserved.