Overexpression of c-erbB-2 is related to a higher expression of vascular endothelial growth factor (VEGF) and constitutes an independent prognostic factor in primary node-positive breast cancer after adjuvant systemic treatment.
The aim of this study was to investigate possible associations between the expression of c-erbB-2 and the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), p53 status, routine breast cancer prognostic factors and survival. Expression of c-erbB-2, VEGF, bFGF, and p53 protein was determined with an enzyme-linked immunosorbent assay (ELISA) in 656 patients with primary breast cancer (median follow-up time of 83 months). In 60 cases, we also used immunohistochemistry (IHC) for c-erbB-2 evaluation, to be used as a reference for the ELISA. Overexpression of c-erbB-2 was significantly related to a higher expression of VEGF, lower bFGF content, negative steroid receptor status, and a high S-phase fraction. In multivariate analysis, c-erbB-2 was an independent prognostic factor for relapse-free survival (RFS) and overall survival (OS) in all patients, and in node-positive patients, irrespective of the adjuvant systemic therapy. Combined survival analyses regarding c-erbB-2 and VEGF yielded additional prognostic information.
Linderholm
B
B
Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, SE-161 67 Stockholm, Sweden. barbro.linderholm@cck.ki.se
Andersson
J
J
Lindh
B
B
Beckman
L
L
Erlanson
M
M
Edin
K
K
Tavelin
B
B
Grankvist
K
K
Henriksson
R
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012044:Regression Analysis; D013548:Sweden / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A