title: 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.
abstract: The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS.
authors.affiliation: Northeastern Ontario Regional Cancer Center, Sudbury, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bewick
authors.forename: M
authors.initials: M
authors.lastname: Conlon
authors.forename: S
authors.initials: S
authors.lastname: Gerard
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: A M
authors.initials: AM
authors.lastname: Parissenti
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Glück
authors.forename: R M
authors.initials: RM
authors.lastname: Lafrenie
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases