Annals of Oncology 14:406-413, 2003
© 2003 European Society for Medical Oncology
Original Paper |
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?
1 Hôpitaux Universitaires de Genève, Geneva, Switzerland; 2 EORTC Data Center, Brussels; 3 Institut J. Bordet, Brussels, Belgium; 4 Netherlands Cancer Institute, Amsterdam, The Netherlands; 5 Institut Bergonié, Bordeaux, France; 6 NCIC Clinical Trials Group, Kingston, Canada; 7 Hospitais da Universidade, Coimbra, Portugal; 8 Centre Henri Becquerel, Rouen, France; 9 University Hospital, Leuven, Belgium
Received 9 September 2002; revised 15 October 2002; accepted 19 November 2002
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.
Key words: breast cancer, locally advanced/inflammatory breast cancer, neoadjuvant chemotherapy, p53
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