The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

  • Woolston C
  • Zhang L
  • Storr S
 et al. 
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Abstract

Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre-treatment needle core biopsy and post-anthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase, thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) pi, theta and alpha, catalase and manganese superoxide dismutase. GST pi (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P=0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments.

Author-supplied keywords

  • Adult
  • Anthracyclines/ therapeutic use
  • Antineoplastic Agents/ therapeutic use
  • Biopsy, Large-Core Needle
  • Breast Neoplasms/ diagnosis/metabolism/therapy
  • Carcinoma, Ductal, Breast/metabolism/ secondary/th
  • Carcinoma, Lobular/drug therapy/metabolism/ second
  • Chemotherapy, Adjuvant
  • Enzymes/metabolism
  • Female
  • Great Britain/epidemiology
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes/pathology
  • Lymphatic Metastasis
  • Mastectomy
  • Middle Aged
  • Oxidation-Reduction
  • Prognosis
  • Survival Rate
  • Treatment Outcome
  • Tumor Markers, Biological/metabolism

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Authors

  • C M Woolston

  • L Zhang

  • S J Storr

  • A Al-Attar

  • M Shehata

  • I O Ellis

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