Identification of BRCA1-associated DNA Repair Dysfunction in Patients With Early Triple Negative Breast Cancer Treated With Neoadjuvant Platinum-based Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- The pathological complete response rate to neoadjuvant platinum-based chemotherapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients, age ≥18 years≤75;
- •Histologically confirmed invasive ER-, PR-, and HER2-negative (triple- negative) adenocarcinoma of the breast;
- •Clinical stage T1-2, N0-1, M0.
排除标准
- •Previous treatment for this breast cancer
- •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
- •Pregnancy or breast-feeding
研究组 & 干预措施
Neoadjuvant platinum-based chemotherapy
Doxorubicin, Paclitaxel, Cisplatin
干预措施: Doxorubicin, Paclitaxel, Cisplatin (Drug)
结局指标
主要结局
The pathological complete response rate to neoadjuvant platinum-based chemotherapy
时间窗: after 8 weeks of neoadjuvant chemotherapy
Pathologic treatment response will be assessed in correlation with BRCA1-associated DNA repair dysfunction signature.
次要结局
- Disease-free survival(3 years)
- Clinical responses to neadjuvant chemotherapy(after 8 weeks of neoadjuvant chemotherapy)
研究者
Mona Frolova
Research Associate of Department of Clinical Pharmacology and Chemotherapy
Russian Academy of Medical Sciences