Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.

Journal Article

PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.

Full Text

Duke Authors

Cited Authors

  • Harris, LN; Liotcheva, V; Broadwater, G; Ramirez, MJ; Maimonis, P; Anderson, S; Everett, T; Harpole, D; Moore, MB; Berry, DA; Rizzeri, D; Vredenburgh, JJ; Bentley, RC

Published Date

  • March 15, 2001

Published In

Volume / Issue

  • 19 / 6

Start / End Page

  • 1698 - 1706

PubMed ID

  • 11250999

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/JCO.2001.19.6.1698

Language

  • eng

Conference Location

  • United States