title: Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?
abstract: Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10-20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angiogenesis, cancer cell proliferation, steroid receptor expression, c-erbB-2 oncoprotein overexpression, p53 protein nuclear accumulation or bcl-2 antiapoptotic protein expression, can predict failure of local therapy. We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy. In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively). In multivariate analysis, the microvessel density and the c-erbB-2 status were independent and significant factors related to local relapse (P=0.001, t-ratio 3.36 and P=0.02, t-ratio 2.26, respectively). Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression. High angiogenesis, however, was linked with local relapse regardless of the radiotherapy regimen.
authors.affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: G
authors.initials: G
authors.lastname: Galazios
authors.forename: E
authors.initials: E
authors.lastname: Sivridis
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012008:Recurrence; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53