Preneoplasia in mammary tumorigenesis

Abstract

It is axiomatic that cancers in epithelial organs arise via multiple intermediate stages. This concept is termed multistage carcinogenesis and is based upon both clinical and experimental observations over the past 40 years in practically all major epithelial organs [1–3]. The intermediate stages have been labeled with various terms, the most common terms being preneoplastic or premalignant. Recently it has been recognized that the stage of preneoplasia itself represents a progression of several stages [4]. The past 10 years have witnessed the application of molecular biology approaches to examine basic questions in mammary carcinogenesis. These approaches, which include the development and characterization of transgenic mouse models and transgenic gland models; the successful development of cell culture systems to establish mammary epithelial cell lines of preneoplastic and neoplastic phenotypes; the identification and elucidation of oncogenes, tumor-suppressor genes, and growth factors; and recognition of the importance of the mammary stroma in mammary epithelial cell function, have provided new insights into the biological and molecular events that underlie the development of mammary carcinogenesis. In light of these new methodologies, the time is appropriate for a review of the preneoplastic state in mammary tumorigenesis. Although this review focuses on the mouse as a model, current results and ideas about rat and human preneoplastic or intermediate stage lesions are also discussed.