Triple-negative Breast Cancer: a New Perspective on Predictive and Prognostic Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 239
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
A single-institutional cohort to determine the prevalence of new immunohistochemical panel in advanced triple-negative submitted to neoadjuvant chemotherapy and its association with response and survival.
详细描述
Background/Rationale: Triple negative breast cancer (TNBC) is known to be a heterogeneous disease, and different molecular sub-classifications are proposed based in specific biomarkers as immunohistochemical (IHC) expression of the androgen-receptor (AR), Epidermal growth Factor Receptor (EGFR), Cytokeratin 5/6 (CK5/6), Cytokeratin14 (CK14), Cytokeratin 17 (CK17), clusters of differentiation 117 (CD 117), p53, Ki67 level, Programmed cell death-ligand 1 (PD-L1) and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes (PD-1+, FOXP3+, CD 4+ or cluster designation 8 (CD8 +), CD 3+, cluster of differentiation 56 (CD56+), cluster designation 68 (CD68+) or CD 14+). Predicting response and survival to neoadjuvant treatment of locally advanced triple-negative breast cancer remains a major challenge. Many doubts still prevail over the role of new biomarkers in predicting different outcomes for tumors with the same stage and morphological characteristics.
Objectives and Hypotheses:
Primary objective: To evaluate the association of the intratumoral lymphocytic infiltrate (TILs) status profile in the core biopsy with complete pathological response (CPR) outcomes to neoadjuvant chemotherapy and progression-free survival (PFS). Secondary objectives: To evaluate the association of the others biomarkers expression profile and the quality of TILs with PFS and CPR. To determine the prevalence of a large immunohistochemical panel (AR, EGFR, CK5/6, CK14, CK17, CD 117, p53, Ki67 level, PD-L1 and PD-L2 in tumor cell membrane and the pattern of tumor infiltrating mono-lymphocytes PD-1+, FOXP3+, CD 4+ , CD8 +, CD 3+, CD56+, CD68+ and/or CD 14+), before and after neoadjuvant chemotherapy. To determine if the negativation of biomarkers after the systemic treatment is associated with CPR and PFS.
Methods:
Study design: A cohort with retrospective data collection and sectional analysis of pathological material.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women older than 18 years
- •Locally advanced TNBC (T3-4, any Node, M0; any Tumor, N1-3, M0)
- •Patients submitted to anthracycline and taxane-based neoadjuvant chemotherapy and then operated between January 2010 and December 2014 at the Brazilian National Cancer Institute.
排除标准
- •Patients with metastatic Breast Cancer;
- •Other non-epithelial histologies of breast cancer;
- •Pure Ductal Carcinoma In Situ diagnoses are not eligible.
- •Patients with scarce material for immunohistochemistry;
- •Other primary synchronous or anachronistic tumors in the breast or other sites;
- •No prior immunotherapeutic, chemotherapeutic or antiandrogenic drugs allowed
- •Patients treated with alternative neoadjuvant chemotherapy regimens (not based on anthracycline and taxane) or with only hormone therapy;
- •Patients who received chemotherapy or who were operated outside the INCA.
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.
The first event defined as local recurrence or distant relapse, or death, whichever come first.
次要结局
- Objective response rate(From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks)
- Determine predictive markers(Approximately 24 weeks: from diagnosis up to surgery.)
- Determine prognostic markers(Approximately 24 months: from diagnosis up to the first event defined as local recurrence or distant relapse, or death, whichever come first through study completion.)
- Clinical Response Rate(From date of first cycle of chemotherapy until completion of neoadjuvant treatment, approximately 16 weeks)
研究者
Jesse Lopes da Silva
MD
Instituto Nacional de Cancer, Brazil