We propose to evaluate the genetic component in the etiology of breast cancer with segregation and linkage analyses. Index cases will be cases with early (<50 years of age) bilateral breat cancer who are currently participating in a study by the USC school of medicine. We will administer a more detailed geneology questionnaire to all index cases, confirm the diagnoses of all possible cases of breast cancer among relatives and obtain one blood sample from each member of multiplex nuclear families. Twenty- eight genetic makers will be determined in the laboratory of Dr. Robert Sparkes at UCLA. By the end of the study, we anticipate having approximately 211 index cases and 50 multiplex families. Segregation analysis will be conducted to test whether or not the distribution of breast cancer in families is consistent with a breast cancer susceptibility gene, and, if so which model best fits our data. We will use an extension of Morton and Maclean's mixed model (MIXMOD) that allows for incomplete ascertainment, selection of certain kinds of multiplex pedigrees, and variable ages of onset. We will then test for linkage between a presumed breast cancer susceptibility gene and 28 genetic marker loci. We will utilize the program LIPED, which can incorporate into the analysis different recombination values in males and females, and incomplete penetrance, which includes age of onset corrections.