Nuclear NF-κB/p65 expression and response to neoadjuvant chemotherapy in breast cancer

J Clin Pathol. 2011 Feb;64(2):130-5. doi: 10.1136/jcp.2010.082966. Epub 2010 Dec 8.

Abstract

Aims: To evaluate the clinicopathological associations and predictive value of the transcription factor NF-κB in a large series of breast cancer patients treated with neoadjuvant chemotherapy.

Methods: A retrospective search of a prospectively maintained database was performed to identify patients. Immunohistochemistry was used to assess the p65 subunit of NF-κB, using nuclear staining as a surrogate of activation.

Results: Nuclear NF-κB expression was found in 26.3% (35/133) of cases. Nuclear NF-κB staining was associated with high histological grade (p=0.05), oestrogen receptor (ER) negativity (p=0.01) and higher Ki67 index (p=0.002). Patients with nuclear NF-κB staining had a higher pathological complete response (pCR) rate than those without (26.5% vs 6.0% respectively, p=0.004); there was no significant association with clinical response or outcome. In an exploratory hypothesis-generating analysis, in the ER+/HER2- subgroup (n=43) a significantly lower clinical response rate was observed in those with nuclear NF-κB staining compared with those who had no nuclear NF-κB staining (14.3% vs 61.0%, p=0.038). There were no pCRs in ER+/ HER2- tumours.

Conclusions: Nuclear NF-κB expression is associated with ER negativity, higher Ki67 index and tumour grade. It was also found to be significantly associated with increased pCR but not clinical response to neoadjuvant chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Nucleus / metabolism
  • Chemotherapy, Adjuvant
  • Cytoplasm / metabolism
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Retrospective Studies
  • Transcription Factor RelA / metabolism*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Transcription Factor RelA
  • ERBB2 protein, human
  • Receptor, ErbB-2