Association of Nuclear Factor-κB Expression with Hormone Receptor Status, HER2, and Histopathological Grade in Advanced Breast Cancer

Abstract

Introduction: Breast cancer is a leading cause of cancer-related mortality in women. Nuclear Factor-κB (NF-κB) pathway, is a key driver of carcinogenesis and tumor progression. This study evaluates the association between NF-κB expression and established biomarkers in advanced breast cancer. Materials and Methods: This prospective, cross-sectional study was conducted at Dr. Wahidin Sudirohusodo Hospital and its network hospitals in Makassar, Indonesia, from April to September 2024. We assessed the association between NF-κB expression (determined by immunohistochemistry) and clinicopathological features in 41 patients with advanced (Stage III and IV) breast cancer. Immunohistochemistry was used to determine the expression of NF-κB, ER, PR, and HER2. Associations were analyzed using Fisher’s Exact Test and multivariable logistic regression to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: A majority of tumors were estrogen receptor (ER)-negative (56.1%), progesterone receptor (PR)-negative (61.0%), and HER2-positive (53.7%). NF-κB positivity was observed in 33/41 patients (80.5%). HER2 positivity was strongly associated with NF-κB positivity (OR = 24.5, 95% CI [2.5, 238.9]; p = 0.012, Fisher’s Exact Test). No significant associations were observed with ER, PR, or histopathological grade. Conclusion: This study identifies a strong and independent association between nuclear NF-κB p65 expression and HER2 positivity in a cohort of patients with advanced (Stage III/IV) breast cancer. Further large-scale, prospective studies are warranted to validate the role of NF-κB as a candidate prognostic biomarker and to explore its utility as a therapeutic target in HER2-positive breast cancer.

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