C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer

Research output: Contribution to journalArticle

Abstract

Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive, Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n = 128) among c-erbB-2 -negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n = 62), the RR was somewhat higher in the c-erbB-.2 overexpressors (33% versus 18%, P = 0. 18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.

Details

Authors
  • J Sjostrom
  • J Collan
  • K von Boguslawski
  • K Franssila
  • NO Bengtsson
  • I Mjaaland
  • Per Malmström
  • B Ostenstad
  • E Wist
  • V Valvere
  • J Bergh
  • D Skiold-Petterson
  • E Saksela
  • C Blomqvist
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • predictive factor, docetaxel, chemotherapy, breast cancer, c-erbB-2
Original languageEnglish
Pages (from-to)535-542
JournalEuropean Journal of Cancer
Volume38
Issue number4
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes