Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA).
OBJECTIVE
Retrospective analysis to assess the prognostic and predictive value of HER-2/ neu expression in breast tumors, quantified by enzyme immunoassay (ELISA).


METHODS
Quantification of HER-2/neu was performed on cytosolic extracts from 914 cases of primary invasive breast carcinomas. Relapse-free and overall survival data were available from 889 patients. The prognostic value of HER-2/neu levels was assessed considering them as a continuous, dichotomic or quartile variable.


RESULTS
Cytosolic HER-2/neu levels ranged widely in breast carcinomas (median: 746.5 NHU/mg; range: 2.8-80,000 NHU/mg protein). HER-2/neu protein levels were significantly higher in either moderately or poorly differentiated tumors, as well as in those showing a ductal histological type, aneuploidy or a high S-phase fraction. There was a significant and positive association between cytosolic and membranous HER-2/neu levels (n=162, r sub S=0.53; P<0.0001). In addition, cytosolic HER-2/neu level correlated weakly with progesterone receptors but not with estrogen receptors. Elevated cytosolic HER-2/neu levels (> or =1,400 NHU/mg protein) were associated with a high probability of both shortened relapse-free survival and overall survival. This same cut-off value was obtained when we divided the overall group of patients in a training set. However, this HER-2/neu value did not achieve any statistical significance in a validation set used to make sure that the cut-off was correct. Nevertheless, when we divided the obtained data into three different groups with respect to the quartile values (Q) of the intratumoral oncoprotein levels (< or = Q1 vs Q1-Q2 vs > Q3), we observed that patients with either low HER-2/ neu levels (< or = Q1) or high HER-2/neu levels (> Q3) had shorter both relapse-free survival and overall survival curves than those patients with intermediate HER-2/neu levels. On the other hand, high HER-2/neu levels predicted a poor response to adjuvant chemotherapy but not to adjuvant hormonal therapy with tamoxifen.


CONCLUSIONS
The results of the present investigation indicate that by quantitatively determining the content of HER-2/neu oncoprotein, groups of high-risk breast cancer patients could be identified, for a more effective clinical management.
Corte
Maria D
MD
Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
Rodil
Juan A
JA
Vázquez
Julio
J
García
Lucia
L
Rodríguez
Juan C
JC
Bongera
Miguel
M
Fernández
José C
JC
González
Luis O
LO
Lamelas
Ma Luz
ML
Allende
Maite
M
García-Muñiz
José L
JL
Fueyo
Antonio
A
Vizoso
Francisco J
FJ
D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000188:drug therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000175:diagnosis* / Q000188:drug therapy; D003600:Cytosol / Q000737:chemistry; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D016019:Survival Analysis
D018719:Erb-b2 Receptor Tyrosine Kinases