Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and meta static breast cancer and predicts poor prognosis. We investigated the expre ssion of HER-2 in patients with metastatic breast cancer undergoing high-do se chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and c orrelated the presence (positive) or absence (negative) of HER-2 overexpres sion in these patients with response to treatment, progression-free surviva l (PFS) and overall survival (OS), The level of HER-2 expression was analyz ed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC s upport, Plasma from peripheral blood was taken at three different time poin ts during the course of treatment and was analyzed using an enzyme immunoas say (EIA) to detect circulating levels of the extracellular portion of HER- 2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment, The level of HER-2 varied dur ing the course of treatment. Following induction chemotherapy (PCT), five p atients who were negative initially, showed overexpression of HER-2, Three patients overexpressed HER-2 only after HDCT/ABSC, Response to treatment wa s similar in patients independent of plasma HER-2 levels, Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank ) and OS (P = 0.003, log rank) after HDCT/ABSC, HER-2 overexpression, patie nt age, estrogen receptor status, progesterone receptor status, and previou s hormone treatment mere assessed by univariate and multivariate analysis, Univariate analysis determined that only HER-2 overexpression correlated si gnificantly with decreases in progression free survival (P = 0.005, Cox reg ression). Decreased overall survival correlated significantly with HER-2 ov erexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039), In multivariate analysi s of these variables, only HER-2 expression levels proved to be of independ ent statistical significance in predicting outcome for both PFS (P = 0.007) and OS (P = 0.002), These results suggest that overexpression of HER-2, me asured by EIA in plasma may predict a shorter PFS and OS in patients with m etastatic breast cancer treated with HDCT and ABSC support.