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

Woolston, Caroline M. and Zhang, Lei and Storr, Sarah J. and Al-Attar, Ahmad and Shehata, Mohamed and Ellis, I.O. and Chan, Stephen Y. and Martin, Stewart G. (2012) The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer. Modern Patholgy, 25 . pp. 1106-1116. ISSN 0893-3952

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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 postanthracycline

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) p, h and a, catalase and manganese superoxide dismutase. GST p (P¼0.05) and catalase

(P¼0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP

(P¼0.017) and thioredoxin reductase (P¼0.022) were independent prognostic factors for distant metastasisfree

survival and TxNIP for overall survival (P¼0.014). 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 (P¼0.000003), 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.

Item Type: Article
Keywords: anthracycline; breast cancer; chemotherapy; glutathione; redox; thioredoxin interacting protein
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences
Depositing User: de Sousa, Mrs Shona
Date Deposited: 01 Apr 2014 09:49
Last Modified: 18 May 2016 03:02
URI: http://eprints.nottingham.ac.uk/id/eprint/2785

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