c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients.
Our aim was to compare the prognostic value of c-erbB-2 gene amplification analyzed by Southern blot with that of protein (p185) over-expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC). Amplification and p185 over-expression were found in 31 (18%) and 51 (30%) BCs, respectively. All but 1 of the tumors showed both amplification and over-expression, while 21 (12%) tumors displayed over-expression without amplification. The risk of death associated with c-erbB-2 gene amplification and p185 over-expression was evaluated by multivariate analysis, taking into account tumor size, histoprognostic grade, hormone receptors and axillary node status. During a mean follow-up of 9.5 (+/-2) years, node involvement (p < 0.001), c-erbB-2 gene amplification (p = 0.02) and negative hormone receptors (p = 0.02) were found to be independent prognostic indicators of the risk of death. Over-expression of p185 with no amplification was not correlated with this risk. When the risk of death associated with c-erbB-2 amplification was studied according to chemo- and hormone therapy, no significant difference was observed between subgroups of subjects. Amplification was also associated (p = 0.02) with the risk of multifocal distant metastases (i.e., metastases detected concomitantly in at least 2 sites) and, thus, with BC aggressiveness. These data show the importance of c-erbB-2 gene amplification in predicting the long-term outcome of patients and in selecting eligible patients for c-erbB-2-targeted therapies.
Riou
G
G
UMGC, Département de Biologie Clinique, Institut Gustave Roussy, Villejuif, France. guy.Riou@wanadoo.fr
Mathieu
M C
MC
Barrois
M
M
Le Bihan
M L
ML
Ahomadegbe
J C
JC
Bénard
J
J
Lê
M G
MG
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012306:Risk; D015996:Survival Rate
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D018719:Erb-b2 Receptor Tyrosine Kinases