HER2 Support Group Forums - HER4 associates with increased sensitivity to Herceptin in MBC

Abstract

Introduction:

HER2 overexpression or rather HER2 gene amplification is indicative for
Herceptin therapy in both metastatic and pre-metastatic breast cancer patients. Patient’s
individual sensitivity to Herceptin treatment however varies enormously and spans from
effectual responsiveness over acquired insensitivity to complete resistance from the
outset. Thus no predictive information can be deduced from HER2 determination so that
molecular biomarkers indicative for Herceptin sensitivity/resistance to Herceptin are
needed to be identified. Both ErbB receptor dependent signalling molecules as well as
HER2 related ErbB receptor tyrosine kinases, known to mutually interact and to crossregulate
each other are prime candidates to be involved in cellular susceptibility to
Herceptin.

Methods:

Using immunohistochemistry and fluorescence in situ hybridisation we
retrospectively investigated primary breast cancer tissues from 48 patients who were
under Herceptin treatment. We quantified the gene copy numbers of all HER receptors
and evaluated their coexpression profile. Moreover the HER2 phosphorylation state, the
ratio of native to truncated HER2, p27(kip1) and PTEN expression were objects of this
study.

Results:

Above all markers investigated in this study Kaplan-Meier and Cox regression
analysis revealed a significant positive impact of HER4 (co-)expression on overall survival
from beginning of antibody therapy. Both HER4 expression and HER4 gene amplification
emerged as independent prognostic markers in Herceptin treated breast cancer patients
and responsiveness to Herceptin turned out to be more efficient if tumour cells show HER4

expression.