Cohort Study of the Relationship Between c-erbB-2 and Cyclin D1 Overexpression, p53 Mutation and/or Protein Accumulation, and Risk of Progression from Benign Breast Disease to Breast Cancer; and Creation of a Bank of Benign Breast Tissue

摘要

Previously, in a case-control study, nested within a cohort of 4,888 women with BBD, we demonstrated that p53 protein accumulation detected by immunohistochemistry was associated with a 2.5-fold increase in the risk of subsequent breast. The purpose of this project was threefold: (1) to collect paraffin-embedded benign breast tissue from the remaining cohort members who were not part of the original case-control study. (2) enlarge the completed case-control study of p53 with an additional cases and matched controls. The tissue biopsies from these subjects were examined for c-erbB-2 overexpression and p53 protein accumulation. For some subjects breast tissue is being examined for the presence of p53 mutations. (3) to examine whether cyclin Dl amplification and/or protein overexpression determined immunohistochemically is a molecular marker of risk of progression from BBD to breast cancer in the enlarged case- control study. The studies supported by this grant demonstrated that (1) cyclin Dl protein overexpression occurs in normal and benign breast tissue; (2) cyclin Dl gene amplification and protein overexpression as detected immunohistochemically were not associated with increased risk of developing breast cancer in the group of individuals studied to date; (3) p53 mutations can occur in benign breast tissue. Also a tissue bank of paraffin-embedded normal or benign breast tissue (total number of individuals: 1900, total number of paraffin blocks: 2,954) was established.