The Effect of P-Glycoprotein (P-gp), Nuclear Factor-Kappa B (Nf-κb), and Aldehyde Dehydrogenase-1 (ALDH-1) Expression on Metastases, Recurrence and Survival in Advanced Breast Cancer Patients

Asian Pac J Cancer Prev. 2019 May 25;20(5):1511-1518. doi: 10.31557/APJCP.2019.20.5.1511.

Abstract

Objective: To investigate the level of three drug resistance proteins; P-glycoprotein 1 (P-gp), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and aldehyde dehydrogenase isoform 1 (ALDH1) expression and their relationship to metastasis, recurrence and survival in advanced breast cancer patients that received neoadjuvant chemotherapy. Methods: This study is a combination of prospective and retrospective cohort study involving one hundred and thirty one cases of advanced stage invasive breast cancer that have received neoadjuvant chemotherapy. Initial biopsy specimens (incisional biopsy or core biopsy) were taken from paraffin blocks. Immunohistochemistry (IHC) was used to detect P-gp, NF-κB, and ALDH1 expression. Prospectively analysed patients were followed for five years and evaluated for recurrence and death. Results: The expression of P-gp has no significant statistical correlation to metastases (p = 0.659), recurrence (p = 0.862) and survival (p = 0.835) in advanced stage breast cancer patients who received neoadjuvant chemotherapy. Similarly, ALDH1 was not correlated to metastases (p=0.120), recurrence (p = 0.186) and survival (p = 0.254) statistically. We found that NF-κB expression showed a significant correlation to metastases (p=0.004), recurrence (p = 0.016) and overall survival (p = 0.041) in advanced stage breast cancer patients after neoadjuvant chemotherapy. Conclusion: NF-κB expression is a potential marker that can be used to assess or to predict increasing risk of metastases, recurrence and survival in advanced stage breast cancer patients who receive neoadjuvant chemotherapy.

Keywords: Breast cancer; neoadjuvant chemotherapy; P-gp; NF-κB; ALDH1.

Publication types

  • Multicenter Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adult
  • Aged
  • Aldehyde Dehydrogenase 1 Family
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Humans
  • Isoenzymes / metabolism*
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neoadjuvant Therapy / methods
  • Neoplasm Metastasis / pathology*
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Prospective Studies
  • Retinal Dehydrogenase / metabolism*
  • Retrospective Studies

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Isoenzymes
  • NF-kappa B
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase