Precursors and preinvasive lesions of the breast: the role of molecular prognostic markers in the diagnostic and therapeutic dilemma

Precursors and preinvasive lesions of the breast include atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular neoplasia (LN). There is a significant debate regarding the classification, diagnosis, prognosis and management of these lesions. This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. It reviews the implication of a variety of molecules in the continuum of breast lesions: estrogen receptors (ER-alpha and ER-beta), c-erb-B2 (Her2/neu), p53, Ki-67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta), p27 (Kip1), p16 (INK4a), p21 (Waf1), vascular endothelial growth factor (VEGF). With respect to the aforementioned molecules, this article reviews their pathophysiological importance, and puts the stress on whether they confer additional risk for invasive breast cancer or not. This knowledge has the potential to be of importance in the therapeutic decisions presenting in the common clinical practice.