Activation of nuclear factor-kappa B is linked to resistance to neloadjuvant chemotherapy in breast cancer patients

C. Montagut, I. Tusquets, B. Ferrer, J. M. Corominas, B. Bellosillo, C. Campas, M. Suarez, X. Fabregat, E. Campo, P. Gascon, S. Serrano, P. L. Fernandez, A. Rovira, J. Albanell*

*Corresponding author for this work

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Abstract

The nuclear factor (NF)-kappa B system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kappa B in breast cancer, we aimed to study the value of basal NF-kappa B/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kappa B/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kappa B/p65 subcellular expression. We studied NF-kappa B/p65, a well-characterised member of the NF-kappa B family that undergoes nuclear translocation when NF-kappa B is activated. Activation of NF-kappa B (i.e. nuclear NF-kappa B/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kappa B/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kappa B/p65 nuclear staining. Moreover, the number of patients with NF-kappa B/p65 activation increased after chemotherapy exposure. It is concluded that NF-kappa B/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kappa B activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kappa B inhibitors to prevent or overcome chemoresistance in breast cancer.

Original languageEnglish
Pages (from-to)607-616
Number of pages10
JournalEndocrine Related Cancer. PMID: 19776290.
Volume13
Issue number2
DOIs
Publication statusPublished - Jun 2006

Keywords

  • RELA TRANSCRIPTION FACTOR
  • SURGICAL ADJUVANT BREAST
  • PREOPERATIVE CHEMOTHERAPY
  • INDUCED APOPTOSIS
  • TUMOR
  • DOXORUBICIN
  • THERAPY
  • EXPRESSION
  • PROJECT
  • LOCALIZATION

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