Until recently, there has been little knowledge on the growth control of oe
strogen receptor (ER)-negative ductal carcinoma in situ (DCIS) and invasive
breast cancer. The recent development of DCIS models, such as transgenic m
ice, cell-line xenograft models and, importantly, in vivo human DCIS xenogr
aft models has facilitated the investigation and understanding of the contr
ol of growth of early pre-invasive breast lesions.
Recent studies have shown that ER-negative DCIS, unlike ER-positive DCIS, i
s hormone independent and does not respond to anti-oestrogen treatment. Mor
eover, DCIS of the comedo type utilises type I tyrosine kinase growth facto
rs, such as epidermal growth factor receptor (EGFR) and c-erbB-2, in recept
or signalling for growth. New data underscore the importance of EGFR as the
major modulating growth factor receptor in the control of proliferation in
the breast.
Pre-clinical studies performed on human DCIS xenografts in nude mice sugges
t a potential role for EGFR tyrosine kinase inhibitors (EGFR-TKIs). More sp
ecifically, ZD1839, a novel orally active and selective EGFR-TKI, has been
shown to produce a response in DOIS through a decrease in epithelial prolif
eration. These findings have enhanced our knowledge of signal transduction
pathways in cancer and indicate that tyrosine kinase blockade of EGFR has p
otential for the treatment and chemoprevention of DCIS.
It is hoped that further advances in this area and evaluation of EGFR-TKIs
in Phase II/III clinical trials will allow their therapeutic potential as a
nticancer agents to be appreciated.