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

C Montagut1, I Tusquets, B Ferrer

  • 1Medical Oncology Department, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona 08035, Spain.

Endocrine-Related Cancer
|May 27, 2006
PubMed

Insights

Nuclear factor kappa B (NF-kappaB) activation in breast cancer predicts resistance to chemotherapy. NF-kappaB levels increased post-treatment, suggesting it as a target for overcoming chemoresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The nuclear factor kappa B (NF-kappaB) system is implicated in cancer development and chemotherapy resistance.
  • Preclinical models suggest NF-kappaB as a potential anticancer therapeutic target.

Purpose of the Study:

  • To clinically validate NF-kappaB/p65 as a predictor of neoadjuvant chemotherapy resistance in breast cancer.
  • To investigate the pharmacodynamic changes in NF-kappaB/p65 expression after chemotherapy.

Main Methods:

  • Immunohistochemistry was used to assess NF-kappaB/p65 subcellular expression in pre- and post-chemotherapy tumor samples.
  • 51 locally advanced breast cancer patients receiving anthracycline- and/or taxane-based neoadjuvant chemotherapy were studied.

Main Results:

  • Pre-treatment nuclear NF-kappaB/p65 staining indicated chemoresistance, with a 20% response rate versus 91% in patients without staining (P=0.002).
  • Complete pathological response was observed only in patients lacking pre-treatment NF-kappaB/p65 nuclear staining.
  • NF-kappaB/p65 activation increased in patients post-chemotherapy.

Conclusions:

  • NF-kappaB/p65 activation, detected by immunohistochemistry, is a predictive biomarker for neoadjuvant chemotherapy resistance in breast cancer.
  • Chemotherapy can induce NF-kappaB activation in a subset of breast cancer patients.
  • These findings support the clinical development of NF-kappaB inhibitors to enhance chemotherapy efficacy.

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