1. ¹Division of Oncology, Department of Medicine, University Hospital of Patras, Rion, Greece
2. ²Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece
3. ³Hellenic Cooperative Oncology Group, Data Office, Athens, Greece
4. ⁴Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece
5. ⁵Siemens Healthcare Diagnostics, Cologne, Germany
6. ⁶Laboratory of Biostatistics, University of Athens School of Nursing, Athens, Greece
7. ⁷Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece
8. ⁸Second Department of Internal Medicine, 'Attikon' University Hospital, Athens, Greece
9. ⁹Laiko General Hospital, University of Athens School of Medicine, Athens, Greece
10. ¹⁰Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece
11. ¹¹Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
12. ¹²Department of Surgery, University of Athens School of Medicine, Athens, Greece
13. ¹³Oncology Department, Hippokration Hospital, Athens, Greece
14. ¹⁴First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece
15. ¹⁵First Department of Medical Oncology, Hygeia Hospital, Athens, Greece

Correspondence: Dr AK Koutras, Division of Oncology, Department of Medicine, University Hospital of Patras, Patras Medical School, Rion 26504, Greece. E-mail: angkoutr@otenet.gr

¹⁶These two authors have contributed equally to this work

Received 1 August 2008; Revised 7 October 2008; Accepted 11 October 2008; Published online 4 November 2008.

Abstract

The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT–PCR). The overall concordance between kRT–PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT–PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.