Hanson HA, Leiser CL, Madsen MJ, et al. - Given that the utility of family-based designs and high-risk pedigrees for detection of high- and intermediate-risk germline breast cancer susceptibility genes has been shown earlier, however, a major barrier preventing progress is genetic heterogeneity, and therefore, researchers define two new family-based approaches to decrease heterogeneity in the Utah Population Database, to demonstrate the wide utility as well as potential power of multi-source databases. In the first approach, the focus was on using pedigree-informed breast tumor phenotypes in gene mapping. The identification of families with similar pleiotropies was the focus of the second approach. A genomewide significant breast cancer locus at 2q13 was discovered using the first approach. Five multi-cancer risk patterns were revealed by applying the second approach. Overall, findings revealed that genes for breast cancer could be mapped by pedigree-informed tumor phenotypes. The existence of several distinct cancer pleiotropies for high-risk breast cancer pedigrees was indicated.