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.

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., Chan, S. Y., & 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: https://nottingham-repository.worktribe.com/output/710009
• Publisher URL: http://www.nature.com/modpathol/journal/v25/n8/full/modpathol201260a.html
• Contract Date: Apr 1, 2014