Circulating HER-2/erbB-2/c-neu (HER-2) extracellular domain as a prognostic factor in patients with metastatic breast cancer: Cancer and Leukemia Group B Study 8662. Academic Article uri icon

Overview

MeSH

  • Adult
  • Female
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

MeSH Major

  • Breast Neoplasms
  • Receptor, ErbB-2

abstract

  • The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M(r) 185,000 transmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resistance or sensitivity to specific treatment. We evaluated circulating levels of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of circulating HER-2 levels regarding endocrine therapy or chemotherapy. Plasma samples from 242 patients were assayed for circulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 was correlated with clinical data gathered from these patients while they were participating in prospective Cancer and Leukemia Group B (CALGB) therapeutic protocols for metastatic breast cancer. Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (> or =10.5 ng/ml). ECD/HER-2 was significantly associated with tumor burden, progesterone receptor levels, and presence of visceral metastases. Patients with elevated pretreatment levels had a significantly shorter OS but not time-to-progression than did those with ECD/HER-2 levels <10.5 ng/ml in univariate analysis. In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (mainly anthracycline-containing regimens), OS did not differ significantly. Rates of response to either endocrine therapy or chemotherapy were similar for patients with elevated and nonelevated ECD/HER-2 levels. ECD/HER-2 levels are elevated in 35-40% of patients with metastatic breast cancer. Elevated ECD/HER-2 levels are associated with a poorer prognosis in these patients. However, no predictive role for ECD/HER-2 was identified, either for endocrine therapy or for anthracycline-based chemotherapy in the metastatic setting.

publication date

  • September 2001

has subject area

  • Adult
  • Breast Neoplasms
  • Female
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2
  • Survival Analysis
  • Time Factors
  • Treatment Outcome

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 11555582

Additional Document Info

start page

  • 2703

end page

  • 2711

volume

  • 7

number

  • 9