NEW DIRECTIONS IN BREAST-CANCER RESEARCH

Research in breast cancer extends in many directions, stimulated by co ncerns related to the high incidence of the disease and the relative u npredictability of its clinical course. Examples of work in several di rections are presented here arranged by four levels of analysis. 1) Mo lecular, intracellular events (molecular genetics). Recent identificat ion of genes that predispose to breast cancer, and the isolation of th ose genes and their protein products, permit investigations of the mos t critical issues: the roles of these genes in normal development and breast differentiation, and how their alteration permits or contribute s to tumor initiation. Thus, we expect that understanding the function s of the genes involved in inherited susceptibility to breast cancer w ill also be informative for sporadic breast cancers. 2) Cellular biolo gy (cellular models for preneoplastic disease). We examine models of b reast cancer development and ask how they help to validate a morpholog ic sequence for human breast neoplasia and whether they permit investi gation of how to modify disease progression. Two useful models, one in transgenic mice and the other using human breast stem cells capable o f 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 ves sels, etc.). This leads naturally to questions of how neighboring tiss ues and cytokines may modify tumor growth. 4) The individual as an org anism 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.