ERBB2 Amplification Is Associated With Tamoxifen Resistance in Steroid-Receptor Positive Breast Cancer

Cancer Lett. 1994 Jun 30;81(2):137-44. doi: 10.1016/0304-3835(94)90194-5.

Abstract

Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.

Publication types

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

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Drug Resistance
  • ErbB Receptors / genetics*
  • Female
  • Gene Amplification*
  • Humans
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogenes*
  • Receptor, ErbB-2
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tamoxifen / therapeutic use*

Substances

  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • ErbB Receptors
  • Receptor, ErbB-2