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.

This article has been cited by other articles:

				P. M. Harari, G. W. Allen, and J. A. Bonner Biology of Interactions: Antiepidermal Growth Factor Receptor Agents J. Clin. Oncol., September 10, 2007; 25(26): 4057 - 4065. [Abstract] [Full Text] [PDF]

				R. Ho, J. E. Minturn, T. Hishiki, H. Zhao, Q. Wang, A. Cnaan, J. Maris, A. E. Evans, and G. M. Brodeur Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor Cancer Res., November 1, 2005; 65(21): 9868 - 9875. [Abstract] [Full Text] [PDF]

				I. Chu, K. Blackwell, S. Chen, and J. Slingerland The Dual ErbB1/ErbB2 Inhibitor, Lapatinib (GW572016), Cooperates with Tamoxifen to Inhibit Both Cell Proliferation- and Estrogen-Dependent Gene Expression in Antiestrogen-Resistant Breast Cancer Cancer Res., January 1, 2005; 65(1): 18 - 25. [Abstract] [Full Text] [PDF]

				G. Vlahovic and J. Crawford Activation of Tyrosine Kinases in Cancer Oncologist, December 1, 2003; 8(6): 531 - 538. [Abstract] [Full Text] [PDF]

				P. A. Davol, R. Bagdasaryan, G. J. Elfenbein, A. L. Maizel, and A. R. Frackelton Jr. Shc Proteins Are Strong, Independent Prognostic Markers for Both Node-Negative and Node-Positive Primary Breast Cancer Cancer Res., October 15, 2003; 63(20): 6772 - 6783. [Abstract] [Full Text] [PDF]

				G. Atalay, F. Cardoso, A. Awada, and M. J. Piccart Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer Ann. Onc., September 1, 2003; 14(9): 1346 - 1363. [Abstract] [Full Text] [PDF]