title: Tumour response to preoperative anthracycline-based chemotherapy in operable breast cancer: the predictive role of p53 expression.
abstract: The aim of this retrospective study was to identify markers capable of predicting pathological complete (pCR) and overall clinical tumour response to preoperative anthracycline-based chemotherapy and clinical outcome in women with operable breast cancer. Therefore, we used the pre-treatment core biopsies from 107 patients who were enrolled in the EORTC trial 10902 to analyse tumour characteristics and the oncogenic markers Bcl-2, p53, ER, PgR, HER2, and p21. Median follow-up was 7 years (95% confidence interval [CI], 6.89-7.45). pCR was seen in seven patients (6.5%) and was associated with improved overall survival (hazards ratio, 0.39; 95% CI, 0.05-2.56; P = 0.30). In multivariate logistic regression analysis, pCR was independently predicted by p53 overexpression estimated by immunohistochemistry (odds ratio [OR], 16.83; 95% CI, 1.78-159.33; P = 0.01). Fifty-eight patients showed clinical tumour response (>50% decrease in tumour size), however responders experienced no benefit in clinical outcome. Clinical tumour response was independently predicted by p53 overexpression (OR, 5.57; 95% CI, 1.58-19.65; P = 0.008) and small clinical tumour size (OR, 10.26; 95% CI, 2.01-52.48; P = 0.005). In multivariate Cox regression analysis, negative pathological lymph node status, low tumour grade and use of tamoxifen showed improved overall survival. In conclusion, our data suggest p53 expression is of predictive significance in anthracycline-containing chemotherapeutic regimens.
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: J Sven D
authors.initials: JS
authors.lastname: Mieog
authors.forename: Jos A
authors.initials: JA
authors.lastname: van der Hage
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijuer
authors.forename: Cornelius J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D011300:Preoperative Care; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D016159:Tumor Suppressor Protein p53