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Randomized Controlled Trial Multicenter Study Clinical Trial
Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: are there molecular markers in the primary tumour that predict for 5-year clinical outcome?
- H Bonnefoi, S Diebold-Berger, P Therasse, A Hamilton, M van de Vijver, G MacGrogan, L Shepherd, N Amaral, C Duval, R Drijkoningen, D Larsimont, and M Piccart.
- Hôpitaux Universitaires de Genève, Geneva, Switzerland. Herve.Bonnefoi@hcuge.ch
- Ann. Oncol. 2003 Mar 1;14(3):406-13.
BackgroundLocally advanced and/or inflammatory breast cancer (LABC) is a heterogeneous disease. Molecular markers may help to understand this heterogeneity. This paper reports the results of a study assessing the potential prognostic or predictive value of HER-2, p53, cyclinD1, MIB1, ER and PgR expression by immunohistochemistry from patients included in an EORTC-NCIC-SAKK trial.Patients And MethodsA total of 448 patients with a cytological or histological diagnosis of LABC were randomised into a trial comparing two anthracycline-based neoadjuvant regimens. Chemotherapy was followed by standard locoregional therapy. Survival was comparable in both arms. We collected and analysed centrally paraffin-embedded tumour specimens from 187 (72.5%) of 258 patients that had a histological diagnosis.ResultsOf the patients included in this molecular marker study 114 relapsed and 91 died. In the multivariate analysis p53 positivity was associated with a shorter progression-free survival [hazard ratio (HR) = 1.96; 95% CI 1.33-2.91; P = 0.0008) and a shorter overall survival (HR = 1.98; 95% CI 1.28-3.06; P = 0.002). PgR positivity predicted for a longer overall survival (HR = 0.54; 95% CI 0.35-0.83; P = 0.0045).Conclusionsp53 was an independent factor predicting for survival. In order to clarify whether p53 is a pure prognostic and/or a predictive factor, a phase III trial is being conducted (EORTC 10994/BIG 00-01 study) using functional assay in yeast from frozen tumour samples.
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