Studies of epidermal growth factor receptor inhibition in breast cancer

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.