The Characterization and Treatment of Aggressive Breast Cancer
Abstract
Several groups have demonstrated that women with BRCA1 germline mutations are more likely to have breast cancers that are basal-like by gene expression profiling. While BRCA1 germline mutations are uncommon, and contribute to fewer than 5% of breast cancer cases, our lab has demonstrated that methylation of the BRCA1 promoter occurs to some degree in almost 50% of high-grade, hormone receptor negative sporadic tumors. As promoter methylation leads to transcriptional repression, we propose that such tumors will be sensitive to DNA damaging agents and resistant to microtubule inhibitors, given the role that BRCA1 plays in both DNA repair and cell cycle. My laboratory has generated preliminary in vitro data that demonstrates breast cancer cells with BRCA1 promoter methylation and low expression levels are three-fold more sensitive to cisplatin and ten times more resistant to paclitaxel, as compared to cells with normal BRCA1 expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA469602
Entities
People
- Rita Nanda
Organizations
- University of Chicago