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Background <p>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(<i>BRCA1</i>) is ubiquitously expressed, it is not clear why <i>BRCA1</i> mutations overwhelmingly predispose to breast and ovarian cancers. Estrogen has been proposed to promote the survival of <i>BRCA1</i>-deficient cells under oxidative stress by activating nuclear factor erythroid-2-related factor 2 (<i>NRF2</i>), potentially driving malignant transformation. This study investigates the role of estrogen and <i>NRF2</i> expression in <i>BRCA1</i>-mutated breast cancer.</p> Methods <p>We analyzed 70 formalin-fixed, paraffin-embedded (FFPE) tissue samples (tumor and adjacent non-tumoral) from 15 <i>BRCA1</i>-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. <i>NRF2</i> expression was quantified using qRT-PCR, while estrogen activity was indirectly assessed via immunohistochemical (IHC) analysis of focal adhesion kinase (FAK) protein expression.</p> Results <p><i>NRF2</i> was significantly overexpressed in <i>BRCA1</i>-mutated tumors compared to controls (p = 0.036). In contrast, no significant difference in estrogen-mediated FAK expression was observed between <i>BRCA1</i>-mutated and control tumors.</p> Conclusions <p>Our findings indicate that <i>NRF2</i> upregulation is a distinguishing feature of <i>BRCA1</i>-mutated breast cancer, suggesting its potential involvement in tumorigenesis. These results offer new paths into targeted prevention and therapeutic strategies for <i>BRCA1-</i>mutation carriers.</p>

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NRF2 expression level and estrogen function in BRCA1-mutated breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Zeinab Derismahafi,
  • Dariush Farhud,
  • Amirhossein Razavirad,
  • Ahad Muhammadnejad,
  • Behnaz Jahanbin,
  • Shirin Farivar,
  • Reza Shirkoohi

摘要

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.