Overexpression of nuclear factor kappa B (NF-кB) protein as a risk factor for anthracyclin chemoresistance in luminal a subtype locally advanced breast cancer (LABC) at Sanglah General Hospital, Bali - Indonesia

Abstract

Background: Around 68.6% of women who have breast cancer seek medical treatment at a locally advanced stage (LABC), where the neoadjuvant chemotherapy (NAC) modality is the initial choice therapy. Luminal A was recorded as the subtype with the chemotherapy response being the most resistant among others. The cause of chemoresistance is multi-factorial, and several studies correlate this condition with several anti-apoptotic agents expressed in the nucleus of cancer cells, especially nuclear factor-kappa B (NF-кB). The NF-κB transcription factor as an anti-apoptotic agent in some cancers blocks the apoptotic pathway through the extrinsic and intrinsic pathways. NF-κB plays a vital role in the development of chemoresistance. Understanding the NF-κB pathway and perceiving more about the cellular characteristics of LABC is very important to develop NF-κB inhibitors as therapy. NF-κB as a transcription factor can be considered a promising research target because it can affect oncogenes' transcription and play an essential role in prognostic and predictive biomarkers. This study was conducted to determine whether NF-κB overexpression is a risk factor for anthracycline-based neoadjuvant chemoresistance in Luminal A subtype LABC patients at Sanglah General Hospital.Methods: An unpaired case-control study was conducted at Sanglah General Hospital. The research subjects were 40 people, divided into case groups (chemoresistance) and control groups (chemosensitive). Hereafter the NF-κB H-Score was carried out by IHC examination. Data are presented in table form and analyzed by Chi-square test or Fischer exact.Results: Samples of cases with NF-κB overexpression were obtained 13 (65%), compared with the control group 7 (35%) (p<0.05). Multivariate analysis has shown that NF-κB overexpression is an independent factor against anthracycline-based chemotherapy resistance in advanced LABC patients with local luminal subtypes with p=0.013; OR 3.45 (95% CI=2.94-12.65).Conclusion: NF-κB expression in Luminal A subtype LABC can be used as a predictor for anthracycline-based neoadjuvant chemoresistance. NF-κB overexpression is a predictor factor for NAC chemoresistance in luminal A subtype LABC.