Rapid advances in our ability to comprehensively examine cancer genomes have revealed that cancer results from an accumulation of genetic damage that is unique for each tumor. Consequently, new therapies that directly target abnormalities in cancer cells must be personalized to match the singular genetic composition of an individual patient’s cancer. To achieve this goal, new ways must be found to rapidly assess genomic damage in tumors and identify those that drive malignant behavior. To meet this challenge, Basic Sciences investigator Ian Macara and his laboratory have devised a new screen to rapidly assess clinically important genetic abnormalities in breast cancer. Their screen exploits the fact that mouse breast stem cells can grow and develop into complete mammary glands when transplanted into a mouse of the same genetic background. Using cells from mice genetically predisposed to breast cancer results in development of tumors in the transplanted glands after period of about 9 months. The Macara lab developed a way to rapidly screen up to 1000 genes normally involved in cell growth and signaling for their ability to make tumors appear in transplanted glands more rapidly. Their approach identified five genes that drive the more rapid growth of breast cancer in this model. More detailed examination of one of these genes (GTF2IRD1) revealed how it influences cell growth and confirmed that it is associated with aggressive breast, lung, and ovarian cancer in human patients. This new assay provides an important foundation from which to explore the full range of genes that drive breast cancer. The work is published in the journal Cell Reports [Y. Huo, et al. (2016), Cell Rep., 15, 2089].