P53 Mutation Analysis to Predict Tumor Response in Patients Undergoing Neoadjuvant Treatment for Locally Advanced Breast Cancer
Abstract
The two most effective classes of chemotherapeutic drugs in breast cancer are the anthracyclines and the taxanes, which differ in mechanisms of action and resistance. P53 may mediate responsiveness to these drugs. P53 mutations status has had limited usefulness as a predictive tumor marker given the technical complexity of previous methods to determine it, however the development of p53 Genechip technology has made high-throughput mutation analysis more feasible. In an ongoing multiinstitutional prospective trial that is not supported by this award, breast cancer patients receiving neoadjuvant chemotherapy using these drugs have serial response assessments and tumor sampling for research purposes. This project involves analyzing he banked tumor specimens for p53 mutations using the Genechip method. We hypothesize that p53 status of the primary tumor will predict response to anthracycline- based and taxane-based chemotherapy given at different times in the same patient. Progress to date includes optimizing the Genechip method of p53 mutation analysis for core biopsy specimens, successful scaling down of DNA requirements for such assays allowing evaluation of small tumor biopsy samples, and optimizing methods for p53 amplification within 1-2 large fragments so that SSCP and sequencing analysis will be feasible despite the small amount of DNA available.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA420856
Entities
People
- Lisa A Carey
Organizations
- University of North Carolina at Chapel Hill