title: The prognostic and predictive power of redox protein expression for anthracycline-based chemotherapy response in locally advanced breast cancer.
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 post-anthracycline 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) π, θ and α, catalase and manganese superoxide dismutase. GST π (P=0.05) and catalase (P=0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P=0.017) and thioredoxin reductase (P=0.022) were independent prognostic factors for distant metastasis-free survival and TxNIP for overall survival (P=0.014). 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 (P=0.000003), 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.
authors.affiliation: Department of Academic Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Woolston
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Attar
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shehata
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Chan
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D062005:Biopsy, Large-Core Needle; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D017024:Chemotherapy, Adjuvant; D004798:Enzymes / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D010084:Oxidation-Reduction; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004798:Enzymes