Hereditary Breast Cancer Clinical Trial
Official title:
Comparative, Multicenter Study Estimating Association Between Germline DNA-repair Genes Mutations and PD-L1 Expression Level in Breast Cancer
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.
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.
To date, it is widely accepted that 5-10% of BC cases are represented by hereditary types,
i.e. mediated by germline pathogenic mutations in genes of DNA reparation pathways.
Hereditary breast cancer (HBC), as well as ovarian cancer (OC), сaused by mutations in genes
BRCA1, BRCA2, CHEK2, TP53 и PTEN, and others. Thus, one of the promising directions here is
to understand the inter-relation among germline pathogenic mutations associated with HBC, and
activity of PD-L1. It would allow to optimize selection of anti-PD-L1 therapy, by forming
group of patients (matching criteria of HBC) with high level of PD-L1 expression in cancer
cells and tumor-infiltrating lymphocytes.
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