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| ID | Type | Description | Link |
|---|---|---|---|
| TNNP 001 | Other Identifier | Russian Cancer Research Center named after N.N.Blokhin RAMS |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neoadjuvant platinum-based chemotherapy | Experimental | Doxorubicin, Paclitaxel, Cisplatin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxorubicin, Paclitaxel, Cisplatin | Drug | Doxorubicin 25 mg/m2, IV weekly. Number of Cycles: 8 Paclitaxel 100 mg/m2, IV weekly. Number of Cycles: 8. Cisplatin 30 mg/m2, IV weekly. Number of Cycles: 8. |
| Measure | Description | Time Frame |
|---|---|---|
| The pathological complete response rate to neoadjuvant platinum-based chemotherapy | Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature. | after 8 weeks of neoadjuvant chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free survival | 3 years | |
| Clinical responses to neadjuvant chemotherapy | after 8 weeks of neoadjuvant chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen | after 8 weeks of neadjuvant chemotherapy |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Russian Cancer Research Center named after N.N.Blokhin RAMS | Moscow | 115478 | Russia |
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| Label | URL |
|---|---|
| Breast Cancer, Neoadjuvant Chemotherapy | View source |
| Doxorubicin, Paclitaxel, Cisplatin | View source |
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| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| D017239 | Paclitaxel |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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