title: A pilot study to investigate the role of the 26S proteasome in radiotherapy resistance and loco-regional recurrence following breast conserving therapy for early breast cancer.
abstract: Breast conserving therapy is a currently accepted method for managing patients with early stage breast cancer. However, approximately 7% of patients may develop loco-regional tumour recurrence within 5 years. We previously reported that expression of the 26S proteasome may be associated with radio-resistance. Here we aimed to analyse the 26S proteasome in a pilot series of early breast cancers and correlate the findings with loco-regional recurrence. Fourteen patients with early breast cancer who developed loco-regional recurrence within 4 years of completing breast conserving therapy were selected according to strict criteria and compared with those from 14 patients who were disease-free at 10 years. Decreased expression of the 26S proteasome was significantly associated with radio-resistance, manifested as the development of a loco-regional recurrence within 4 years of breast conserving therapy (p = 0.018). This small pilot study provides further suggestion that the 26S proteasome may be associated with response to radiotherapy.
authors.affiliation: Cancer Biology Proteomics Group, Postgraduate Medical Institute of the University of Hull, Hull, UK.
authors.forename: Dalia
authors.initials: D
authors.lastname: Elfadl
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Hodgkinson
authors.forename: Ervine D
authors.initials: ED
authors.lastname: Long
authors.forename: Lucy
authors.initials: L
authors.lastname: Scaife
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Drew
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lind
authors.forename: Lynn
authors.initials: L
authors.lastname: Cawkwell
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D010865:Pilot Projects; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease