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
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.