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

Phase 2
18 Years
75 Years
Open (Enrolling)
Early Triple Negative Breast Cancer

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Trial Information

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The pathological complete response rate to neoadjuvant platinum-based chemotherapy

Outcome Description:

Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.

Outcome Time Frame:

after 8 weeks of neoadjuvant chemotherapy

Safety Issue:



Russia: Ethics Committee

Study ID:

TNNP 001



Start Date:

August 2011

Completion Date:

Related Keywords:

  • Early Triple Negative Breast Cancer
  • Breast Neoplasms