The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer
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 speci...
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| Format: | Article |
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Nature Publishing Group
2012
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| Online Access: | https://eprints.nottingham.ac.uk/2785/ |
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| author | Woolston, Caroline M. Zhang, Lei Storr, Sarah J. Al-Attar, Ahmad Shehata, Mohamed Ellis, Ian O. Chan, Stephen Y. Martin, Stewart G. |
| author_facet | Woolston, Caroline M. Zhang, Lei Storr, Sarah J. Al-Attar, Ahmad Shehata, Mohamed Ellis, Ian O. Chan, Stephen Y. Martin, Stewart G. |
| author_sort | Woolston, Caroline M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:19:33Z |
| format | Article |
| id | nottingham-2785 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:19:33Z |
| publishDate | 2012 |
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| recordtype | eprints |
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| spelling | nottingham-27852020-05-04T16:32:59Z https://eprints.nottingham.ac.uk/2785/ 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. 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. Nature Publishing Group 2012-04-06 Article PeerReviewed Woolston, Caroline M., Zhang, Lei, Storr, Sarah J., Al-Attar, Ahmad, Shehata, Mohamed, Ellis, Ian O., 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 anthracycline; breast cancer; chemotherapy; glutathione; redox; thioredoxin interacting protein http://www.nature.com/modpathol/journal/v25/n8/full/modpathol201260a.html doi:10.1038/modpathol.2012.60 doi:10.1038/modpathol.2012.60 |
| spellingShingle | anthracycline; breast cancer; chemotherapy; glutathione; redox; thioredoxin interacting protein Woolston, Caroline M. Zhang, Lei Storr, Sarah J. Al-Attar, Ahmad Shehata, Mohamed Ellis, Ian O. Chan, Stephen Y. Martin, Stewart G. The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title | The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title_full | The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title_fullStr | The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title_full_unstemmed | The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title_short | The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| title_sort | prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer |
| topic | anthracycline; breast cancer; chemotherapy; glutathione; redox; thioredoxin interacting protein |
| url | https://eprints.nottingham.ac.uk/2785/ https://eprints.nottingham.ac.uk/2785/ https://eprints.nottingham.ac.uk/2785/ |