The Characterization and Treatment of Aggressive Breast Cancer
Final rept. 23 Apr 2004-22 Apr 2007
CHICAGO UNIV IL MEDICAL SCHOOL
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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 cancers our lab has demonstrated that methylation occurs in up to 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. Using the alamar blue cytotoxicity assay and five breast cancer cell lines my laboratory has demonstrated that one of two BRCA1 methylated cell lines is significantly more sensitive to cisplatin and more resistant to paclitaxel as compared to other human breast cancer cell lines with normal BRCA1 expression. These findings are currently being translated into a clinical trial where the BRCA1 methylation status of a patients tumor will be correlated to response of the tumor to platinum-based therapy.
- Medicine and Medical Research