New directions in breast cancer research.

Research in breast cancer extends in many directions, stimulated by concerns related to the high incidence of the disease and the relative unpredictability of its clinical course. Examples of work in several directions are presented here arranged by four levels of analysis. 1) Molecular, intracellular events (molecular genetics). Recent identification of genes that predispose to breast cancer, and the isolation of those genes and their protein products, permit investigations of the most critical issues: the roles of these genes in normal development and breast differentiation, and how their alteration permits or contributes to tumor initiation. Thus, we expect that understanding the functions of the genes involved in inherited susceptibility to breast cancer will also be informative for sporadic breast cancers. 2) Cellular biology (cellular models for preneoplastic disease). We examine models of breast cancer development and ask how they help to validate a morphologic sequence for human breast neoplasia and whether they permit investigation of how to modify disease progression. Two useful models, one in transgenic mice and the other using human breast stem cells capable of culture and xenograft growth, are now available. 3) Tissue and organ (the tumor and its local environment). We look at the relationship of the tumor cell population to its local environment (stroma, blood vessels, etc.). This leads naturally to questions of how neighboring tissues and cytokines may modify tumor growth. 4) The individual as an organism and member of a population (hormonal rise and chemoprevention). We address identification of the primarily hormonal risk factors and a possible related mode of cancer prevention.