The candidate has recently accepted a junior faculty member position in epidemiology at the Fred Hutchinson Cancer Research Center. His immediate goals are to pursue his interests in breast cancer etiology, and to further his research skills and experience. His long term goal is to establish a career that will advance scientific knowledge concerning cancer epidemiology and prevention. The proposed research career development plan involves advanced training in genetic and molecular epidemiology, research pathology, and biostatistics. The candidate will also develop his grant writing skills and submit both R03 and R01 grants during the proposed award period. Two epidemiologic research projects involving the use of biomarkers that expand on preliminary work on contralateral breast cancer (CBC) conducted by the candidate and his mentor are proposed. The strongest risk factor for CBC is age at diagnosis of a woman's first primary breast cancer, as women diagnosed before age 45 have a 5.4-fold greater risk of CBC compared to the risk women never diagnosed with breast cancer have of developing a first breast cancer. However, little is known about what factors predispose young breast cancer patients to develop CBC. Our pilot data suggest that among women diagnosed with a first breast cancer before age 45 years, the 45% of subjects with a c-erbB-2 positive tumor have a 1.7-fold (95% confidence interval: 1.0-3.0) excess risk of CBC. Through two studies, a nested case-control study of women diagnosed with a first breast cancer from 1996-2007 at age 21-49 years, and a cohort study of 1,285 women, diagnosed with a first breast cancer at 21-45 years of age from 1983-1992 and followed through 2001 for the diagnosis of CBC, we will evaluate the role that c-erbB-2 plays in CBC etiology. The specific hypotheses to be tested are: 1) Does c-erbB-2 expression in first breast cancers diagnosed in young women increase their CBC risk? 2) Is c-erbB-2 expression in first breast cancers predictive of its expression in CBCs? 3) Are there patient, tumor, or treatment factors that influence the expression of c-erbB-2 and other tumor markers in CBCs? 5) How do other tumor markers expressed by first tumors correlate to their expression in CBCs? If we confirm our finding that c-erbB-2 is predictive of CBC, this would support our hypothesis that c-erbB-2 plays an important role in the etiology of CBC and indicate that women with c-erbB-2 positive tumors should be closely monitored for CBC. [unreadable] [unreadable]