Until recently, there has been little knowledge on the growth control of oestrogen receptor (ER)-negative
ductal carcinoma in situ (
DCIS) and invasive
breast cancer. The recent development of
DCIS models, such as transgenic mice, cell-line xenograft models and, importantly, in vivo human
DCIS xenograft models has facilitated the investigation and understanding of the control of growth of early pre-invasive breast lesions. Recent studies have shown that ER-negative
DCIS, unlike ER-positive
DCIS, is
hormone independent and does not respond to anti-oestrogen treatment. Moreover,
DCIS of the comedo type utilises type I
tyrosine kinase growth factors, such as
epidermal growth factor receptor (EGFR) and c-erbB-2, in receptor 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 suggest a potential role for EGFR
tyrosine kinase inhibitors (EGFR-TKIs). More specifically,
ZD1839, a novel orally active and selective EGFR-TKI, has been shown to produce a response in
DCIS through a decrease in epithelial proliferation. These findings have enhanced our knowledge of signal transduction pathways in
cancer and indicate that
tyrosine kinase blockade of EGFR has potential 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
anticancer agents to be appreciated.