Comparative, Multicenter Study Estimating Association Between Germline DNA-repair Genes Mutations and PD-L1 Expression Level in Breast Cancer
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 390
- 试验地点
- 1
- 主要终点
- Diagnostic performance of PD-L1 expression in breast cancer
研究概览
简要总结
This is a multicentre, non-interventional, prospective study to be carried out in representative oncology departments / institutions in order to determine the association between the presence of germline DNA-repair genes mutations and PD-L1 expression level in tumour and immune cells in breast cancer. No additional procedures besides those already used in the routine clinical practice will be applied to the patients.
详细描述
Breast cancer (BC) occupies the first place among malignancy in females (29.9% of all tumors in female patients in Russian Federation in 2015) [1].
One of the most perspective direction of the oncotherapy is anticancer immunotherapy - employment of inhibitors of immune checkpoints. Immune checkpoints inhibitors (such as anti-PD-1 and anti-PD-L1 antibodies) have shown good clinical efficiency in clinical research to cure such malignant tumor with high mutation load, as melanoma, lung cancer, and others.
One of the hypothesis of such effect states that, usually, more cancer neoantigens are synthetized in the tumors with high mutation load (driven by genome instability), causing severe lymphoid infiltration [2-3]. This situation is balanced by overexpression of such inhibitors of the immune response as PD-1 and PD-L1 [4 - 6].
Breast cancer - is relatively heterogenic tumor, with different genetic, morphological and phenotypic forms.
Despite relatively low expression of PD-L1 in BC in general, there are reasons to believe that genetic instability, driven by mutations in genes involved in DNA repair, can increase the immunogenicity and, thus, the expression of PD-L1 in BC.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
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
- •The voluntary obtained informed consent signed by both the subject and the investigator.
- •Females 18 years age or more.
- •Histologically confirmed BC with known hormone receptors and HER2neu receptors status, Grade of tumor, diagnosed before enrolment into the study.
- •Availability of FFPE tissue samples received prior to any type of antitumor treatment start. Tumour tissue samples must be satisfied IHC requirements for PD-L1 testing.
- •Ability of blood samples receiving for NGS germline mutations testing.
- •Completed medical records (stage, receptors status, demographic data)
排除标准
- •Any evidence of uncontrolled system pathology, active infections, active bleeding diathesis, renal graft, including virus hepatitis B, C or HIV.
结局指标
主要结局
Diagnostic performance of PD-L1 expression in breast cancer
时间窗: January 2018-January 2019
Number of samples of PD-L1 high expression in tumor and immune cells in FFPE breast tumor tissue and number of samples of PD-L1 low expression in tumor and immune cells in FFPE breast tumor tissue . The report will be represented as "PD-L1 high" or "PD-L1 low".
次要结局
- Diagnostic performance of inherited gene mutations in breast cancer(January 2018-January 2019)
- Association between germline DNA-repair genes mutations and PD-L1 expression level in in breast cancer(January 2018-January 2019)