BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
|ClinicalTrials.gov Identifier: NCT01672671|
Recruitment Status : Completed
First Posted : August 27, 2012
Last Update Posted : November 3, 2015
|Condition or disease||Intervention/treatment||Phase|
|Early Triple Negative Breast Cancer||Drug: Doxorubicin, Paclitaxel, Cisplatin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy|
|Study Start Date :||August 2011|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||November 2015|
Experimental: Neoadjuvant platinum-based chemotherapy
Doxorubicin, Paclitaxel, Cisplatin
Drug: Doxorubicin, Paclitaxel, Cisplatin
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.
- The pathological complete response rate to neoadjuvant platinum-based chemotherapy [ Time Frame: after 8 weeks of neoadjuvant chemotherapy ]Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.
- Disease-free survival [ Time Frame: 3 years ]
- Clinical responses to neadjuvant chemotherapy [ Time Frame: after 8 weeks of neoadjuvant chemotherapy ]
- Number of patients with 3/4 Grade CTC adverse events to assess toxicity and tolerability of the chemotherapy regimen [ Time Frame: after 8 weeks of neadjuvant chemotherapy ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01672671
|Russian Cancer Research Center named after N.N.Blokhin RAMS|
|Moscow, Russian Federation, 115478|