c-erbB-2 Expression and Response to Adjuvant Therapy in Women With Node-Positive Early Breast Cancer

N Engl J Med. 1994 May 5;330(18):1260-6. doi: 10.1056/NEJM199405053301802.

Abstract

Background: The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy.

Methods: Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation.

Results: Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression. No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis. There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression.

Conclusions: There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression. Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • DNA, Neoplasm / analysis
  • Doxorubicin / administration & dosage
  • ErbB Receptors / analysis*
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Proto-Oncogene Proteins / analysis*
  • Receptor, ErbB-2
  • S Phase
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • Doxorubicin
  • Cyclophosphamide
  • ErbB Receptors
  • Receptor, ErbB-2
  • Fluorouracil

Supplementary concepts

  • CAF protocol