HER-2 expression is a prognostic factor in patients with metastatic breastcancer treated with a combination of high-dose cyclophosphamide, mitoxantrone, paclitaxel and autologous blood stem cell support

The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated th e clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of hig h-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclit axel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as t he cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high s oluble plasma HER-2 have a significantly poorer overall (OS) and progressio n-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-posi tive (13.0 vs 8.6 months). Univariate analysis showed that patients with li ver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to di sease progression, but not OS. In multivariable analysis, lung metastases c ontributed along with HER-2-positive status to determine a group of patient s with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS.