Association of Adjuvant Radiotherapy of Non-metastatic Breast Carcinoma With Immunomodulation and Circulating Tumor Cell Phenotype in Relation to Patient Age.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Longitudinal quantification of CETCs as well as immunophenotype at specific time points during the course of therapy.
研究概览
简要总结
In a prospective study, the influence of adjuvant radiotherapy in patients with non-metastatic breast carcinoma on the epithelial tumor cells (CETCs) circulating in the blood and their immunohistochemical characteristics depending on age will be investigated. In addition to a histopathological assignment of the CETCs as cells of the primary tumor, major trigger points of the immune system will be exploratively analyzed.
For this purpose, blood samples are taken from the patients at different time points after tumor resection and during adjuvant radiotherapy. In addition to the detection, isolation and genetic characterization of the CETCs, the determination of immunological biomarkers by immunophenotyping, among other methods, is planned. Furthermore, analyses of tissue from the primary tumor with respect to immunohistochemical features as well as tumor-infiltrating lymphocytes (TILs) are planned. The results will be classified and correlated especially with regard to patient age.
As there are insufficient data available for breast carcinoma regarding radiotherapeutic effects on the immune system depending on patient age, it is of great interest to better understand these molecular biological basics in order to identify potential prognostic biomarkers.
详细描述
The primary aim of this prospective-explorative phase 0 study is to investigate the influence of adjuvant radiotherapy in patients with non-metastatic breast cancer on the circulating epithelial tumor cells (CETCs) in the peripheral blood and their immunohistochemical characteristics in younger high risk (premenopausal) versus older low risk (postmenopausal) patients. In addition, the immunophenotype will be determined using peripheral venous blood mononuclear cells (PBMCs) at different time points during the course of therapy and correlated with the results of CETC analysis. The aim of the study is to identify prognostic and predictive biomarkers for early stage breast cancer patients. No therapeutic consequences will be derived.
For this purpose, the phenotype and molecular biological profile of CETC will be investigated and compared with the corresponding characteristics of the primary tumor in order to assign the tumor cells detected in the peripheral blood to the primary tumor. In this context, the number of tumor-infiltrating lymphocytes (TILs) will be correlated with circulating tumor cells and immunophenotype.
Another goal is the characterization of individually isolated CETC by RT-PCR. The expression of selected marker genes involved in metastatic processes will be investigated during the course of therapy and compared with that of the primary tumor to identify therapy-associated changes. The in vitro cultivation of so-called tumor spheres and their characterization as a sign of a therapy-resistant phenotype is a secondary objective of the study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Primary diagnosis histologically confirmed invasive breast carcinoma pT1-4 pN0 or pN+ cM0
- •curative-intended breast-conserving therapy (BET) ± (neo-) adj. system therapy with subsequent adjuvant radiotherapy of the breast ± lymphatic drainage system planned
- •informed consent of the patient
排除标准
- •DCIS, Inflammatory breast carcinoma
- •Recurrence situation
- •Presence of distant metastases
- •Second malignancies < 10 years prior to diagnosis of breast carcinoma
- •Prior exposure to radiotherapy
研究组 & 干预措施
premenopausal patients
干预措施: Adjuvant radiotherapy (Radiation)
premenopausal patients
干预措施: neoadjuvant and adjuvant chemotherapy (Drug)
postmenopausal patients
干预措施: Adjuvant radiotherapy (Radiation)
postmenopausal patients
干预措施: neoadjuvant and adjuvant chemotherapy (Drug)
结局指标
主要结局
Longitudinal quantification of CETCs as well as immunophenotype at specific time points during the course of therapy.
时间窗: observation period 2 years
Measurement of CETC count / µl blood in the course of therapy and correlation with the cell count of detected T and B cells / µl blood.
Age-dependent influence of radiotherapy on circulating epithelial tumor cell counts (CETC) and immunophenotype (PBMC).
时间窗: observation period 2 years
Measurement of CETC count / µl blood in the course of therapy and correlation with patient age.
Comparison of immunohistochemical parameters of the primary tumor with the immunohistochemical and cytological parameters of CETC
时间窗: observation period 2 years
Comparison of PD-L1 expression of primary tumor cells with CETC in percent. Comparison of hormone receptor status (estrogen, progesterone) values of primary tumor and CETC in percent.
次要结局
- Recurrence-free survival (RFS)(observation period 3 years follow up)
研究者
Matthias Mäurer
Dr. med.
University of Jena