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

Citation
Df. Hayes et al., 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, CLIN CANC R, 7(9), 2001, pp. 2703-2711
Citations number
56
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
9
Year of publication
2001
Pages
2703 - 2711
Database
ISI
SICI code
1078-0432(200109)7:9<2703:CH(EDA>2.0.ZU;2-U
Abstract
Purpose: The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M-r 185,000 tra nsmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resi stance or sensitivity to specific treatment. We evaluated circulating level s of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of cir culating HER-2 levels regarding endocrine therapy or chemotherapy. Experimental Design: Plasma samples from 242 patients were assayed for circ ulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 wa s correlated with clinical data gathered from these patients while they wer e participating in prospective Cancer and Leukemia Group B (CALGB) therapeu tic protocols for metastatic breast cancer. Results: Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (g reater than or equal to 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 < 10.5ng/ml in univariate analysis. In univariate but not multivariate sub set analyses, among patients treated with endocrine therapy (megestrol acet ate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (m ainly 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. Conclusions: ECD/HER-2 levels are elevated in 35-40% of patients with metas tatic 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 chemot herapy in the metastatic setting.