CYCLIN D1 AS BIOMARKER OF BREAST CANCER RISK

DESCRIPTION: (Adapted from the Investigator's Abstract) The proposed research project seeks to further develop an existing Western blot assay that can detect the cyclin D1 protein in blood samples and to validate cyclin D1 in blood as a biomarker for the presence of breast cancer. The validation of bloodborne tumor derived proteins, such as cyclin D1, as biomarkers that are predictive for the presence of breast cancer, would allow us to develop new strategies for the detection, management and follow up of breast cancer. In the U.S., the incidence of breast cancer has been rising steadily, with over 182,0000 new cases in 1996; it now affects 1 in 9 women during the course of their lifetime. Early detection through mammography has been shown to reduce mortality due to breast cancer, but new technologies that can be used in conjunction with mammography are needed. Additionally approaches that can provide presurgical information on likely receptor status or prognosis would greatly aid in making treatment choices. Lastly, the use of tumor derived proteins as biomarkers may be useful in patient follow up to predict recurrence or metastases. Cycylin D1 is an oncoprotein overexpressed in 50-60% of breast tumors, and its overexpression is strongly associated with estrogen receptor positive tumors and with a better prognosis. We have developed a Western blot assay that can detect cyclin D1 in blood plasma samples. Our preliminary studies show that this protein can be detected in 60% o breast cancer patients and its presence is strongly associated with breast cancer status. A three year study is proposed to further refine this assay, complete the necessary laboratory validation steps and to validate cyclin D1 as a predictive biomarker in an ongoing molecular epidemiologic case-control study of breast cancer. Cyclin D1 will be analyzed in stored blood plasma samples from 100 cases, 100 benign breast disease controls, and 100 healthy controls; the association between cyclin D1 levels and case-control status will be assessed. Additionally, to investigate the correlation between tissue overexpression of cyclin D1 and the presence of the protein in blood, stored tissue sections from cases and BBD controls will be assays for cyclin D1. Lastly the relationship between the presence of cyclin D1 protein in blood and estrogen receptor status and other tumor characteristics such as size and stage will be evaluated. This transitional study will take the necessary steps in validating blood levels of cyclin D1 as a marker for the presence of breast cancer. Once validated, this biomarker could be useful in the early detection, management and follow up of breast cancer.