Genetically engineered mouse models of mammary intraepithelial neoplasia

Foci of atypical mammary epithelium have been associated with breast cancer in many species including mouse and man. The advent of targeted genomics has led to the creation of numerous genetically engineered mice (GEM) which display focal atypical lesions associated with mammary cancer. Some early lesions in GEM have a remarkable morphological similarity to pre-cancers in humans. While the malignant potential of atypical foci have been thoroughly documented in the non-GEM by tissue transplantation, a review of the literature reveals that precursor lesions in GEM remain incompletely described and only partially documented. Their validation as appropriate models of human breast preneoplasia awaits classical transplantation studies. Here, we review the literature characterizing early lesions of GEM models of mammary cancer, discuss the principles of the Focality, Atypia, and Association and present an introduction of mammary transplantation for model Validation.