The association of HER-2/neu amplification with breast cancer recurrence.
OBJECTIVE
Amplification of the HER-2/neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival.


METHODS
Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/neu testing. The mean follow-up was 56 months.


METHODS
Large, urban, tertiary care hospital.


METHODS
From 1995 to 1999, a consecutive sample of 190 patients with breast cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncogene by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but received their treatment elsewhere. All patients tested for HER-2/neu after diagnosis with breast cancer in 1999 (n = 47) were excluded from analysis because of short follow-up time. One patient was excluded who had in situ ductal carcinoma. The remaining 93 patients were analyzed.


RESULTS
Of 93 patients, 40 (43%) had gene amplification. Overall, patients with oncogene amplification had a shorter median disease-free interval (22 months) compared with controls (40 months) (P =.003). Analysis by the Cox regression model showed that the HER-2/neu status remained significantly associated with time to relapse even after adjusting for age and tumor grade (P =.002; adjusted relative risk, 2.4; 95% confidence interval, 1.4-4.4). No association was found between gene amplification and tumor grade (P =.98), estrogen/progesterone receptor status (P = .29 and P = .43, respectively), or lymph node status (P = .98). Seventy-two patients (77%) eventually had disease recurrence, with 18 (25%) of these recurring locally.


CONCLUSIONS
The HER-2/neu oncogene is an independent prognostic indicator of a subset of breast cancers that are at high risk of early recurrence, regardless of tumor grade, estrogen/progesterone receptor status, and lymph node status. Patients amplifying the HER-2/neu oncogene have a shorter disease-free survival than patients without the oncogene.
Carr
J A
JA
Department of General Surgery K-8, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202-2689, USA.
Havstad
S
S
Zarbo
R J
RJ
Divine
G
G
Mackowiak
P
P
Velanovich
V
V
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate