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Nuclear NF-κB/p65 expression and response to neoadjuvant chemotherapy in breast cancer
  1. Robin L Jones1,
  2. Federico Rojo2,3,4,
  3. Roger A'Hern1,
  4. Nadia Villena4,5,
  5. Janine Salter1,
  6. Josep Maria Corominas2,4,
  7. Sonia Servitja4,5,
  8. Ian E Smith6,
  9. Ana Rovira4,5,
  10. Jorge S Reis-Filho7,
  11. Mitchell Dowsett1,
  12. Joan Albanell4,5,8
  1. 1Academic Department of Biochemistry, Royal Marsden Hospital, London, UK
  2. 2Pathology Service, Hospital del Mar-IMAS, Barcelona, Spain
  3. 3Pathology Service, Fundación Jiménez-Díaz, Madrid, Spain
  4. 4Cancer Research Program, IMIM-Hospital del Mar, Barcelona, Spain
  5. 5Medical Oncology Service, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
  6. 6Breast Unit, Royal Marsden Hospital, London, UK
  7. 7Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
  8. 8Autonomous University of Barcelona, Barcelona, Spain
  1. Correspondence to Joan Albanell, Medical Oncology Service, Hospital del Mar, Parc de Salut Mar Passeig Maritim 25-29, Barcelona 08003, Spain; jalbanell{at}hospitaldelmar.cat and Dr Robin L Jones, University of Washington/ Fred Hutchinson Cancer Research Center, 825 Eastlake Avenue E, G3630, Seattle 98112, USA; rjones{at}seattlecca.org

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.

  • Breast cancer
  • neoadjuvant chemotherapy
  • NF-κB
  • pathological complete response
  • breast cancer
  • chemotherapy
  • immunohistochemistry

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Footnotes

  • Funding RLJ was funded by the Cridlan Ross Smith Breast Cancer Research Fund. The Royal Marsden Hospital receives funding from the NIHR as a Biomedical Research Centre. JA was partially supported by the Instituto de Salud Carlos III (Intensificación). This work has been supported by PI061513, PI09/1296 and PI09/01285 (Spanish Health Ministry Grant ‘Fondo de Investigación Sanitaria’/FEDER) and RTICC 06/0020/109 grant. We also thank DIUE Generalitat de Catalunya (2009SGR321) Fundació Privada Cellex (Barcelona) for a generous donation to the Hospital del Mar Medical Oncology Service.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Royal Marsden Hospital and Hospital del Mar-IMAS.

  • Provenance and peer review Not commissioned; externally peer reviewed.