BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy

NCT ID: NCT01672671

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2015-11-30

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.

Conditions

Early Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant platinum-based chemotherapy

Doxorubicin, Paclitaxel, Cisplatin

Group Type: EXPERIMENTAL

Doxorubicin, Paclitaxel, Cisplatin

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Female patients, age ≥18 years≤75;

2. Histologically confirmed invasive ER-, PR-, and HER2-negative (triple- negative) adenocarcinoma of the breast;

3. Clinical stage T1-2, N0-1, M0.

Exclusion Criteria

1. Previous treatment for this breast cancer

2. History of malignancy treated with curative intent within the previous 5 years with the exception of skin cancer, cervical carcinoma in situ, or follicular thyroid cancer. Patients with previous invasive cancers (including breast cancer) are eligible if the treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease

3. Pregnancy or breast-feeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Russian Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Mona Frolova

Research Associate of Department of Clinical Pharmacology and Chemotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Russian Cancer Research Center named after N.N.Blokhin RAMS

Moscow, , Russia

Countries

Russia

Related Links

http://www.ncbi.nlm.nih.gov/pubmed

Breast Cancer, Neoadjuvant Chemotherapy

http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp

Doxorubicin, Paclitaxel, Cisplatin

Other Identifiers

TNNP 001

Identifier Type: OTHER

Identifier Source: secondary_id

TNNP 001

Identifier Type: -

Identifier Source: org_study_id