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

Abstract

Summary:C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (Ͼ0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was 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, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS Correspondence: Dr S Glück, Depts Oncology, Medicine, and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331, 29th Street NW, Calgary, Alberta, Canada Received 18 August 1998; accepted 5 May 1999 (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

“…This analysis showed a significantly shorter PFS and OS for patients with high level of ECD as compared to those with low levels. [18][19] Kim et al 20 reported similar results in assessing HER2 status by IHC. In contrast to our and the previously quoted studies, comparing ECD and HER2 status evaluated by IHC and FISH on primary tumors in patients treated with HD alkylating agents after anthracycline-based induction chemotherapy, Harris et al 22 concluded that ECD only can identify a subset of patients at worse prognosis, while IHC and FISH were not correlated with outcome.…”

“…The majority of these studies showed a worse outcome for HER2-positive patients. [18][19][20][21][22] Overall, these studies included 274 patients with HER2 assessed on the tumor, and the patients were treated with a variety of induction regimens, not including taxanes.…”

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

“…Further, recent data suggest that the level of HER-2 expression may not only be a prognostic factor, but may also predict response to different treatments. [6][7][8]16,17 The prognosis of patients with metastatic breast cancer is very poor with less than 5% surviving 10 years after detection of metastasis. 18 As a result, the main objective of treatments Progression-free survival Figure 1 Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) of patients with metastatic breast cancer (n = 46) following HDCT and ABSCT.…”

“…These results support our earlier findings on the prognostic power of HER-2 in the HDCT treatment of patients with metastatic breast cancer. 7 …”

“…[1][2][3] Overexpression of the HER-2 proto-oncogene in patients with node-positive and nodenegative breast cancer correlates with a poorer response and a reduced overall and progression-free survival in patients treated with hormone therapy, adjuvant radiotherapy, adjuvant and high-dose chemotherapy treatment regimens. [4][5][6][7][8] In general, HER-2 overexpression predicts for poor prognosis in breast cancer.…”