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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
11:12

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

Expression of heregulin, phosphorylated HER-2, HER-3 and HER-4 in HER-2 negative breast cancers

Susanne Haas1, Heidrun Gevensleben, Sylvia Rabstein

  • 1Institute of Pathology, Medical Faculty of the University of Bonn, D-53127 Bonn, Germany. susanne.haas@ukb.uni-bonn.de

Oncology Reports
|January 17, 2009
PubMed

Insights

This study found no evidence of HER-2 activation in breast cancers without HER-2 overexpression, suggesting trastuzumab may not benefit HER-2 negative patients. Further research is needed on HRG, HER-3, and HER-4 roles.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • HER-2 amplified breast cancers respond to trastuzumab.
  • Transactivation of HER-2 via phosphorylated HER-2 (pHER-2) and heregulin (HRG) has been hypothesized in HER-2 negative tumors.
  • This suggests potential trastuzumab sensitivity in a subset of HER-2 negative breast cancers.

Purpose of the Study:

  • To investigate the potential transactivation of HER-2 in breast cancers with negative/low HER-2 expression.
  • To analyze the expression of pHER-2, HRG, HER-3, and HER-4 in HER-2 negative breast cancer samples.
  • To determine if these factors are associated with patient survival or clinical factors.

Main Methods:

  • Immunohistochemistry was used to analyze pHER-2, HRG, HER-3, and HER-4 expression.
  • The study included 171 breast cancer samples from the GENICA study with negative/low HER-2 expression.
  • Statistical analysis was performed to assess associations with survival and clinical factors.

Main Results:

  • No expression of pHER-2 was detected in any of the examined tumors.
  • Moderate to strong cytoplasmic staining for HRG, HER-3, and HER-4 was observed in 26%, 39%, and 19% of cases, respectively.
  • No significant association was found between HRG, HER-3, or HER-4 expression and patient survival or clinical prognostic factors.

Conclusions:

  • The study provides no evidence for HER-2 activation in the absence of HER-2 overexpression in breast cancer.
  • The biological function and clinical implications of HRG, HER-3, and HER-4 in HER-2 negative tumors remain unclear.
  • The findings do not support the hypothesis of HER-2 transactivation, thus questioning the potential therapeutic benefit of trastuzumab in HER-2 negative breast cancers.

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