The association of HER-2/neu amplification with breast cancer recurrence

Hypothesis: Amplification of the HER-2/neu oncogene in 25% of breast cancer s is associated with a shortened disease-free survival. Design: Retrospective analysis of a patient population referred to a tertia ry 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 brea st cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncoge ne by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but rece ived their treatment elsewhere. All patients tested for HER-2/neu after dia gnosis with breast cancer in 1999 (n=47) were excluded from analysis becaus e 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 r egression model showed that the HER-2/neu status remained significantly ass ociated 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 a ssociation was found between gene amplification and tumor grade (P=.98), es trogen/progesterone receptor status (P=.29 and P=.43, respectively), or lym ph node status (P=.98). Seventy-two patients (77%) eventually had disease r ecurrence, 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, re gardless of tumor grade, estrogen/progesterone receptor status, and lymph n ode status. Patients amplifying the HER-2/neu oncogene have a shorter disea se-free survival than patients without the oncogene.