Long-term prognostic significance of HER-2/neu in untreated node-negative breast cancer depends on the method of testing.
BACKGROUND
The prognostic significance of HER-2/neu in breast cancer is a matter of controversy. We have performed a study in 101 node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting, and analysed the prognostic significance of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), both separately and in combination, in comparison with traditional prognostic factors.


METHODS
Overexpression was classified semiquantitatively according to a score (0 to 3+) (HER-2_SCO). FISH was used to analyse HER2/neu amplification (HER-2_AMP). Patients classified 2+ by IHC were examined with FISH for amplification (HER-2_ALG). Patients with 3+ overexpression as well as amplification of HER-2/neu were positive for the combined variable HER2_COM. These variables were compared with tumour size, histological grade and hormone receptor status.


RESULTS
HER-2_SCO was 3+ in 20% of all tumours. HER-2_ALG was positive in 22% and amplification (HER-2_AMP) was found in 17% of all tumours. Eleven percent of the tumours showed simultaneous 3+ overexpression and amplification. Only histological grade (relative risk [RR] 3.22, 95% confidence interval [CI] 1.73-5.99, P = 0.0002) and HER-2_AMP (RR 2.47, 95% CI 1.12-5.48, P = 0.026) were significant for disease-free survival in multivariate analysis. For overall survival, both histological grade (RR 3.89, 95% CI 1.77-8.55, P = 0.0007) and HER-2_AMP (RR 3.08, 95% CI 1.24-7.66, P = 0.016) retained their independent significance.


CONCLUSIONS
The prognostic significance of HER-2/neu in node-negative breast cancer depends on the method of testing: only the amplification of HER-2/neu is an independent prognostic factor for the long-term prognosis of untreated node-negative breast cancer.
Schmidt
Marcus
M
Department of Obstetrics and Gynecology, Johannes Gutenberg University, Medical School, Mainz, Germany. MarcusSchmidtMD@aol.com
Lewark
Barbara
B
Kohlschmidt
Nikolai
N
Glawatz
Christiane
C
Steiner
Erik
E
Tanner
Berno
B
Pilch
Henryk
H
Weikel
Wolfgang
W
Kölbl
Heinz
H
Lehr
Hans-Anton
HA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D015203:Reproducibility of Results
D018719:Erb-b2 Receptor Tyrosine Kinases
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