Evaluation of the prognostic and predictive value of HER-1/EGFR in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy

Oncology. 2007;72(5-6):388-96. doi: 10.1159/000113148. Epub 2008 Jan 14.

Abstract

Background: To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy.

Methods: 595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients.

Results: HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07).

Conclusion: The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Epirubicin / administration & dosage*
  • Female
  • Fluorouracil / administration & dosage
  • Genes, erbB-1 / genetics*
  • Humans
  • Immunohistochemistry
  • Methotrexate / administration & dosage
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Predictive Value of Tests
  • Prognosis

Substances

  • Epirubicin
  • Cyclophosphamide
  • Paclitaxel
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen