Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.
In order to investigate the prognostic significance of erbB-2 overexpression, immunohistochemical staining for the erbB-2 protein was performed on sections from paraffin blocks of 292 primary invasive breast cancers obtained from women enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-06. Positive reaction indicative of erbB-2 overexpression was observed on tumor cells in 62 (21%) samples. Women whose cancers were judged to have erbB-2 overexpression had a significantly worse overall survival (P = .0012) with twice the mortality rate of women without detectable erbB-2 expression. No statistically significant effect was evident for disease-free survival (P = .22). In multivariate analysis, detection of erbB-2 overexpression was the second most predictive independent variable for survival after nodal status. Overexpression of erbB-2 was more common among tumors of poor nuclear grade (29%) than those of good nuclear grade (12%). The association of erbB-2 overexpression with decreased survival was evident only among women with tumors of good nuclear grade. In this subgroup, erbB-2 overexpression was associated with an approximately fivefold increase in mortality rate (P = .00001). The combined predictive value of erbB-2 overexpression and nuclear grade was evident regardless of their lymph node status. These results provide evidence that detection of erbB-2 overexpression may be an independent prognostic variable for patient survival. Moreover, when combined with evaluation of nuclear grade, it may be possible to use immunostaining for erbB-2 protein to identify patients at increased risk from within a relatively low-risk group.
Paik
S
S
Medical Breast Cancer Section, National Cancer Institute, Bethesda, MD.
Hazan
R
R
Fisher
E R
ER
Sass
R E
RE
Fisher
B
B
Redmond
C
C
Schlessinger
J
J
Lippman
M E
ME
King
C R
CR
D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002460:Cell Line; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases; D012307:Risk Factors; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases