The Association of HER-2/neu Amplification With Breast Cancer Recurrence

Hypothesis Amplification of the HER-2/ neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival. Design Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/ neu testing. The mean follow-up was 56 months. Setting Large, urban, tertiary care hospital. Patients 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.