Ignite Creation Date:
2024-05-06 @ 12:52 AM
Last Modification Date:
2024-10-26 @ 10:55 AM
Study NCT ID:
NCT01672671
Status:
COMPLETED
Last Update Posted:
2015-11-03
First Post:
2012-08-16
Brief Title:
BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
Sponsor:
Russian Academy of Medical Sciences
Organization:
Russian Academy of Medical Sciences
Study Overview
Official Title:
Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
Status:
COMPLETED
Status Verified Date:
2015-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to assess efficacy of platinum-based neoadjuvant chemotherapy in correlation with BRCA1-associated DNA repair dysfunction in patients with early triple negative breast cancer
Detailed Description:
Recent gene expression profiling of breast cancer has identified specific subtypes with clinical biologic and therapeutic implications The basal-like group of tumors is associated with aggressive behavior and poor prognosis and typically do not express hormone receptors or HER-2 triple-negative phenotype Therefore patients with basal-like cancers do not benefit from currently available targeted systemic therapy
There is a lot of evidence about a link between basal-like breast cancer and BRCA1 deficiency Many clinical characteristics and molecular features are shared by basal-like breast cancers and tumors that arise in carriers of BRCA1 germline mutations
Some studies have indicated that BRCA1 mRNA expression was lower in basal-like sporadic cancers than in controls matched for age and grade BRCA1 is rarely mutated in sporadic breast cancers and therefore it is believed that this may be a result of epigenetic mechanisms such as acquired methylation of the BRCA1 gene promoter or a dysfunction in the pathways that regulate BRCA1 expression such as overexpression of ID4 The profound similarities between hereditary BRCA1-related breast tumors and basal-like tumors strongly implicate a fundamental defect in the BRCA1 or associated DNA-repair pathways p53 PTEN in sporadic basal-like tumors
There is increasing evidence that the BRCA1-related DNA-repair defects especially defective homologous recombination determines sensitivity to certain agents such as platinum salts-based chemotherapy The complexity in downregulation of BRCA1 expression suggests that these approaches may only be effective in the treatment of a subset of sporadic basal-like cancers Identification of specific markers for these cancers will be essential to translate an understanding of defective DNA repair into targeted treatments for this poor prognosis subtype
There is a lot of evidence about a link between basal-like breast cancer and BRCA1 deficiency Many clinical characteristics and molecular features are shared by basal-like breast cancers and tumors that arise in carriers of BRCA1 germline mutations
Some studies have indicated that BRCA1 mRNA expression was lower in basal-like sporadic cancers than in controls matched for age and grade BRCA1 is rarely mutated in sporadic breast cancers and therefore it is believed that this may be a result of epigenetic mechanisms such as acquired methylation of the BRCA1 gene promoter or a dysfunction in the pathways that regulate BRCA1 expression such as overexpression of ID4 The profound similarities between hereditary BRCA1-related breast tumors and basal-like tumors strongly implicate a fundamental defect in the BRCA1 or associated DNA-repair pathways p53 PTEN in sporadic basal-like tumors
There is increasing evidence that the BRCA1-related DNA-repair defects especially defective homologous recombination determines sensitivity to certain agents such as platinum salts-based chemotherapy The complexity in downregulation of BRCA1 expression suggests that these approaches may only be effective in the treatment of a subset of sporadic basal-like cancers Identification of specific markers for these cancers will be essential to translate an understanding of defective DNA repair into targeted treatments for this poor prognosis subtype
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| TNNP 001 | OTHER | Russian Cancer Research Center named after NNBlokhin RAMS | None |