Clinical trial NCT03667612: Endogenous Mechanisms of Inactivation of the Endothelium Tumor
Official title: Endogenous Mechanisms of Inactivation of the Endothelium Tumor
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Cancer
Colon Cancer
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: Institut de Biologie de Lille
First posted: 2018-09-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with:

* a breast cancer
* a colorectal cancer

Brief summary: The role of immunity in the development of cancers, and the associated escape mechanisms, have attracted renewed interest since the publication of tests testing immunological checkpoint inhibitors. One of the steps in the probably least studied immunological response is the penetration of immunocompetent cells within the tumor across the vascular barrier. This infiltration is suggested as a prognostic and predictive marker of treatment response, particularly in triple negative HER2 (Human Epidermal Growth Factor Receptor-2) overexpressing breast cancers. The methods of evaluating these infiltrates are complex and have been the subject of recommendations.

A better understanding of the mechanisms of infiltration of immunity cells within tumors will certainly help to better understand the impact of cancer treatments and develop new therapeutic strategies.

It is this issue of vascular endothelium that Dr. Soncin's team is developing as part of an INCa (Institut National du cancer) project. The egfl7 / VE-statin (vascular endothelial-statin) gene is thought to be involved in transendothelial passage of immune cells from vascular lumen to tumor. Its expression has already been studied in a series of breast cancers. Other markers of endothelial activation are currently being identified.

The main objective of this project will be to better understand the behavior of the endothelium in a population of breast cancer where the infiltrate in immune cells is precisely likely to play a leading role. This retrospective cohort of 250 to 300 cases treated with adjuvant and neoadjuvant will be immunologically characterized using the recommendations of Salgado et al. that a multicentric team of pathologists will take ownership. This evaluation will be counter-appraised.

Once our cohort is immunologically characterized, our project will focus on better understanding the endothelial mechanisms involved: which cells? immunophenotyping of immunity cells. By which vessels? (measurement of densities in blood and lymphatic vessels, density in HEV). By what mechanisms? Do the actors identified in vitro within the Inca project have an in vivo translation

Detailed description: The main objective of this project will be to better understand the behavior of the endothelium in a population of breast cancer where the infiltrate in immune cells is precisely likely to play a leading role. This retrospective cohort of 250 to 300 cases treated with adjuvant and neoadjuvant will be immunologically characterized using the recommendations of Salgado et al., that a multicentric team of pathologists will take ownership. This evaluation will be counter-appraised.

Once our cohort is immunologically characterized, our project will focus on better understanding the endothelial mechanisms involved: which cells? immunophenotyping of immunity cells. By which vessels? (measurement of densities in blood and lymphatic vessels, density in HEV). By what mechanisms? Do the actors identified in vitro within the Inca project have an in vivo translation

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 and over
* Confirmed histological diagnosis of breast carcinoma at localized or metastatic stage or colorectal cancer
* Treated at the Oscar Lambret Center or the Henri Becquerel Center between 1/1/2005 and 31/12/2007
* Having undergone surgery for excision of the primary tumor and / or a metastasis
* resected specimen available
* Patients who gave their consent

Exclusion Criteria:

* History of other cancers
* Breast or colic tumors with other histological profiles
* Patient treated for breast or colonic recurrence

Primary outcomes:
measure: correlation between the expression levels of the genes involved in the regulation of endothelial activation and the degree of tumor-infiltrating lymphocytes
timeFrame: 24 months
Secondary outcomes:
measure: reproducibility of lymphocyte infiltration assessment on H & E slides
timeFrame: 24 months
measure: study of the subgroups of the cohort with a predominant lymphocytes infiltration cancer
timeFrame: 24 months
measure: Cell density description
timeFrame: 24 months
measure: Prognostic value assessment
timeFrame: 24 months
measure: Expression levels of genes involved in the regulation of endothelial activation
timeFrame: 24 months
measure: treatment response data
timeFrame: 24 months
measure: lymphocytic infiltrate data
timeFrame: 24 months
measure: the existence of a BRCA1 and or BRCA 2 mutation (which are tumour suppressor genes)
timeFrame: 24 months
measure: association between lymphocytic infiltrate data and the RER phenotype (the replication error phenotype)
timeFrame: 24 months
measure: The RER phenotype (the replication error phenotype)
timeFrame: 24 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Rouen
country: France
facility: Centre Henri Becquerel
Study officials:
affiliation: Centre oscar Lambret de Lille
name: Géraldine Lauridant, MD
role: PRINCIPAL_INVESTIGATOR
References: