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

Woolston, Caroline M.; Zhang, Lei; Storr, Sarah J.; Al-Attar, Ahmad; Shehata, Mohamed; Ellis, Ian O.; Chan, Stephen Y.; Martin, Stewart G.

Authors

Caroline M. Woolston

Lei Zhang

Sarah J. Storr

Ahmad Al-Attar

Mohamed Shehata

Ian O. Ellis

Stephen Y. Chan

Stewart G. Martin



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 metastasis free 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.

Citation

Woolston, C. M., Zhang, L., Storr, S. J., Al-Attar, A., Shehata, M., Ellis, I. O., …Martin, S. G. (in press). The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer. Modern Pathology, 25, https://doi.org/10.1038/modpathol.2012.60

Journal Article Type Article
Acceptance Date Feb 15, 2012
Online Publication Date Apr 6, 2012
Deposit Date Apr 1, 2014
Publicly Available Date Apr 1, 2014
Journal Modern Patholgy
Electronic ISSN 0893-3952
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 25
DOI https://doi.org/10.1038/modpathol.2012.60
Keywords anthracycline; breast cancer; chemotherapy; glutathione; redox; thioredoxin interacting protein
Public URL http://eprints.nottingham.ac.uk/id/eprint/2785
Publisher URL http://www.nature.com/modpathol/journal/v25/n8/full/modpathol201260a.html
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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