Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy

Cancer. 2007 Aug 1;110(3):509-17. doi: 10.1002/cncr.22825.

Abstract

Background: Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER-2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER-2/neu and serum EGFR in breast cancer patients treated with low-dose chemotherapy.

Methods: Serum levels of HER-2/neu (n = 135) and of EGFR (n = 113) were prospectively determined before the start of chemotherapy, after 2 months of treatment, and when progressive disease was diagnosed.

Results: Elevated (>15 ng/mL) serum HER-2/neu before the start of chemotherapy was not associated with response rate, whereas elevated serum HER-2/neu at 2 months was significantly associated with reduced long-term clinical benefit (24 weeks) (P < .001), as well as changes in HER-2/neu levels between baseline and 2 months (P < .0001). Multivariate analysis identified a >or=20% increase of serum HER-2/neu as an independent factor for progression-free survival (PFS). Kinetics of serum HER-2/neu were significantly associated with PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels of EGFR (<45 ng/mL) were predictive of reduced response rate both at 2 months (P = .031) and after 24 weeks (P = .022). Moreover, they were significantly associated with reduced PFS (P = .016) and OS (P = .015).

Conclusions: Serum HER-2/neu and EGFR may represent useful markers for early prediction of probability of response, PFS, and OS in patients with advanced breast cancer treated with metronomic chemotherapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Cyclophosphamide / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • ErbB Receptors / blood*
  • Female
  • Humans
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / blood*
  • Thalidomide / administration & dosage

Substances

  • Biomarkers, Tumor
  • Thalidomide
  • Cyclophosphamide
  • ErbB Receptors
  • Receptor, ErbB-2
  • Methotrexate