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Bewick et al. 363
INTRODUCTION
The proto-oncogene c-erbB-2/neu HER-2 resides on chromosome 17 and
encodes a 185-kDa transmembrane glycoprotein (designated HER-2) with
intracellular tyrosine kinase activity. 1
HER-2 is a member of the EGF growth factor
receptor family which consists of four closely related family members: the EGF
receptor (EGFR, ERBB1), HER-2 (ERBB2/NEU), HER-3 (ERBB3) and HER-4
(ERBB4). 2
Both homodimers and heterodimers are formed between the various
family members mediating a complex system of signal transduction affecting both
2 - 6
cell proliferation and growth.
The importance of these growth factor recept6rs on the growth and regulation
of breast cancer has been clearly demonstrated. Overexpression and/or amplification
of HER-2 has been found in 20-30% of primary breast tumors and to
varying degrees in other cancers (ovarian, gastric, colorectal, lung, salivary,
bladder, pancreas, endometrial, cervical, oral, and prostate). 7-12
Both HER-2
overexpression and gene amplification have been often found to correlate with
decreased survival, particularly in patients with node-positive breast
cancer. 7-14
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Although HER-2 oncoprotein overexpression correlates with a reduction in
patient survival, only a few studies have evaluated the incidence of HER-2 overexpression
in patients with metastatic breast cancer (MBC) and examined whether
increased levels of this protein indicates a poorer prognosis and/or reduced responsiveness
to systemic treatment. 14-24
In these studies, 30-50% of patients with MBC
have been shown to have elevated levels of circulating (plasma, serum)
extracellular domain of HER-2. 14-19
Overexpression has been shown to correlate
with an increased tumor burden and reduced survival. 14-161822-25
Since EIA is a relatively simple assay commonly used in clinical medicine, the
possibility that elevated levels of extracellular HER-2 could indicate poor
prognosis in patients with MBC is of particular interest.
HDCT followed by ABSC support is rapidly becoming the preferred treatment
for patients with MBC, high-risk stage II and III breast cancer in the U.S. 26
Little
is known about the incidence of HER-2 gene overexpression in patients with MBC
undergoing this treatment and whether increased levels of this protein indicates a
poor prognosis and/or a reduced responsiveness to this treatment.
In this retrospective study, we have examined the incidence of overexpression
and changes in the levels of HER-2 protein in the plasma of 57 patients with
advanced breast cancer treated with HDCT and ABSC support. Results were
analyzed and correlated to response to treatment, progression-free survival (PFS)
and overall survival (OS).