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

Martua Arpollos; Indra Indra; Berti J. Nelwan; Firdaus Hamid; Salman Ardi Syamsu; Elridho Sampepajung; Rina Masadah; Muhammad Faruk

doi:10.31557/apjcc.2026.11.1.25-31

Authors

Martua Arpollos Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Indra Indra Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Berti J. Nelwan Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Firdaus Hamid Department of Clinical Microbiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Salman Ardi Syamsu Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Elridho Sampepajung Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Rina Masadah Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. http://orcid.org/0000-0002-1380-4759
Muhammad Faruk Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. http://orcid.org/0000-0002-7079-4585

DOI:

https://doi.org/10.31557/apjcc.2026.11.1.25-31

Keywords:

breast cancer, hormone receptor status, NF-κB, HER2, histopathological grade

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.