title: C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer.
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.
authors.affiliation: Department of Oncology, Helsinki University Hospital, Haartmaninkatu 4, FIN-00290, Helsinki, Finland. johanna.sjostrom@hus.fi
authors.forename: J
authors.initials: J
authors.lastname: Sjöström
authors.forename: J
authors.initials: J
authors.lastname: Collan
authors.forename: K
authors.initials: K
authors.lastname: von Boguslawski
authors.forename: K
authors.initials: K
authors.lastname: Franssila
authors.forename: N-O
authors.initials: NO
authors.lastname: Bengtsson
authors.forename: I
authors.initials: I
authors.lastname: Mjaaland
authors.forename: P
authors.initials: P
authors.lastname: Malmström
authors.forename: B
authors.initials: B
authors.lastname: Østenstad
authors.forename: E
authors.initials: E
authors.lastname: Wist
authors.forename: V
authors.initials: V
authors.lastname: Valvere
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.forename: D
authors.initials: D
authors.lastname: Skiöld-Petterson
authors.forename: E
authors.initials: E
authors.lastname: Saksela
authors.forename: C
authors.initials: C
authors.lastname: Blomqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D043823:Taxoids
chemical_list: D000077143:Docetaxel; D005472:Fluorouracil; D008727:Methotrexate; D009363:Neoplasm Proteins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids