BACR7
Altered expression of thioredoxin system proteins, in locally advanced breast cancer, predicts response to anthracyclin based chemotherapy.
Caroline Woolston1, Lei Zhang1, Ahmad Al-Attar2, Mohamed Shehata2, Stephen Chan2, Ian Ellis2, Stewart Martin1
1University of Nottingham, UK, 2Nottingham University Hospital NHS Trust, Nottingham, UK
Background
Resistance to neo-adjuvant anthracyclin based chemotherapy (C/T) is seen in approximately 30% of locally advanced breast cancer patients (LAPC). This study examined, as anthracyclines have been associated with generation of reactive oxygen species as a by-product of their action, whether pre-C/T levels of redox proteins could predict response to anthracyclin based C/T. A panel of seven redox proteins were examined:- three members of the thioredoxin (Trx) system (Trx1, Trx Reductase (TrxR1) and TxNIP), Glutathione-S-Transferase (GST) pi and theta, Catalase and MnSOD. The Trx system was of particular interest as a number of novel inhibitors are currently under pre-clinical and clinical evaluation.
Method
Core needle biopsy and post-C/T (6 cycles FEC/FAC) tumour sections were analysed from 80 LAPC cases. Standard immunohistochemical techniques were used to assess protein expression (H-scores) in both pre- and post C/T specimens and results correlated with response (clinical and pathological response as assessed by RECIST criteria), disease free and overall survival (58 months median follow up time).
Results
Levels of Trx, GST-theta and MnSOD were significantly increased after therapy in paired pre/post cases (p<0.001, p=0.023 and p=0.048 respectively). Examining the pre-C/T cohort, significant correlations were obtained between TxNIP expression and progression free (p=0.008) and overall survival (p=0.05) with low expression predicting a worse prognosis. No significance was obtained, with any of the proteins, in respect to clinical response but borderline significance was seen with GST-pi (p=0.068) and Catalase (p=0.058) re. pathological response.
Conclusion
Results suggest that examination of redox proteins, particularly members of the Trx system, may allow prediction of response to FEC/FAC based C/T in LAPC – a larger study is warranted.
Acknowledgements
The authors gratefully acknowledge the Breast Cancer Campaign for funding this work
