Choosing a mouse model: experimental biology in context--the utility and limitations of mouse models of breast cancer.

Genetically engineered mice are critical experimental models for the study of breast cancer biology. Transgenic mice, employing strong mammary epithelial promoters to drive oncogenes, develop carcinomas with phenotypes corresponding to the molecular pathway activated. Gene-targeted (knockout) mice, in which tumor suppressors are deleted, develop mammary neoplasms with phenotypes primarily including patterns seen in spontaneous mouse mammary tumors, albeit at higher rates. Improved genetic engineering, using inducible gene expression, somatic gene transduction, conditional alleles, and crossbreeding for combined/compound genetic engineering yields precise molecular models with exquisite experimental control and phenotypes with comparative pathologic validity. Mammary gland transplantation technology adds a practical and validated method for assessing biologic behavior of selected mammary tissues. Overall, the many mouse models available are a rich resource for experimental biology with phenocopies of breast cancer subtypes, and a variety of practical advantages. The challenge is matching the model to the experimental question.