HER-2/neu oncogene protein and prognosis in breast cancer.
Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.
Tandon
A K
AK
Department of Medicine, University of Texas Health Science Center, San Antonio, 78284-7884.
Clark
G M
GM
Chamness
G C
GC
Ullrich
A
A
McGuire
W L
WL
D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000032:analysis* / Q000235:genetics; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005784:Gene Amplification; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000032:analysis*; D011336:Probability; D011379:Prognosis; D011494:Protein Kinases / Q000032:analysis*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D014408:Biomarkers, Tumor; D009856:Oncogene Proteins, Viral; D011494:Protein Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone