title: Nuclear NF-κB/p65 expression and response to neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: Nadia
authors.initials: N
authors.lastname: Villena
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Corominas
authors.forename: Sonia
authors.initials: S
authors.lastname: Servitja
authors.forename: Ian E
authors.initials: IE
authors.lastname: Smith
authors.forename: Ana
authors.initials: A
authors.lastname: Rovira
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies; D051996:Transcription Factor RelA / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D051996:Transcription Factor RelA; C508053:ERBB2 protein, human