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Abstract:
Several groups have demonstrated that women with BRCA1 mutations are more likely to have breast cancers that are hormone receptor and HER2/neu negative. Our lab has previously demonstrated that BRCA1 promoter methylation occurs to some degree in 30% of all sporadic tumors, and up to 50% of high-grade hormone receptor negative tumors, making it much more common than germline mutation. Given the role of BRCA1 in DNA repair, it is likely that cells deficient in BRCA1 secondary to promoter methylation will have an increased sensitivity to DNA damaging agents. The role of BRCA1 methylation in determining chemosensitivity is not yet known. Previous studies have demonstrated that cells deficient in BRCA1 secondary to mutation are more sensitive to cisplatin than BRCA1 competent cells. We have demonstrated for the first time that cells deficient in BRCA1 secondary promoter methylation are also highly sensitive to cisplatin. As BRCA1 methylation occurs in almost one-half of high-grade hormone receptor negative tumors, it represents a potential therapeutic target in the treatment of a subset of hormone receptor negative breast cancers.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 23 Apr 2004-22 Apr 2005 |
| Pages: |
55 |
| Report Date: |
MAY 2005 |
| Contract Number: |
W81XWH0410545 |
| Report Number: |
A207734 |
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