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?

Abstract

BACKGROUND:

Locally 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 METHODS:

A 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.

RESULTS:

Of 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).

CONCLUSIONS:

p53 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.

• Authors: 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, M Piccart
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 14 Issue 3 Pg. 406-13 (Mar 2003) ISSN: 0923-7534 [Print] England
• PMID: 12598346 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Biomarkers, Tumor
• Ki-67 Antigen
• Receptors, Estrogen
• Receptors, Progesterone
• Tumor Suppressor Protein p53
• Cyclin D1
• Granulocyte Colony-Stimulating Factor
• Epirubicin
• Cyclophosphamide
• Receptor, ErbB-2
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Anthracyclines (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (drug therapy, pathology)
• Cyclin D1 (biosynthesis, blood)
• Cyclophosphamide (administration & dosage)
• Epirubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Gene Expression Regulation, Neoplastic
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Immunohistochemistry
• Infusions, Intravenous
• Ki-67 Antigen (analysis, biosynthesis)
• Middle Aged
• Neoadjuvant Therapy
• Predictive Value of Tests
• Prognosis
• Receptor, ErbB-2 (biosynthesis, blood)
• Receptors, Estrogen (analysis, biosynthesis)
• Receptors, Progesterone (analysis, biosynthesis)
• Survival Analysis
• Treatment Outcome
• Tumor Suppressor Protein p53 (biosynthesis, blood)