Pilot Study of the Predictive Value of TREM1 Expression and Activation in Inflammation and Radio-induced Mammary Fibrosis

Study Overview
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Brief Summary
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Breast cancer is the most common cancer in the world. Half of patients with such cancer are treated with radiation therapy. Some patients will develop cutaneous or subcutaneous fibrosis, more or less bothersome. Several studies have shown a correlation between an inflammatory reaction and a protein, called TREM-1. But to date, no link has been proven between TREM-1 and inflammation / fibrosis in the phenomena of fibrosis induced by radiotherapy in patients with breast cancer. Our study aims to understand the involvement of this TREM-1 protein in the development of fibrosis or radio-epidermis in patients with breast cancer.

Official Title
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Pilot Study of the Predictive Value of TREM1 Expression and Activation in Inflammation and Radio-induced Mammary Fibrosis

Conditions
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Radiation Toxicity, Fibrosis, Breast Cancer

Intervention / Treatment
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* Biological: Blood sampling


Participation Criteria
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Eligibility Criteria
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Group A Patients over 18 years old, Breast cancer (adenocarcinoma in situ or invasive) Non-metastatic disease Radiotherapy after conservative surgery with irradiation of the breast alone and complement on the operating bed (optional) completed two to six months ago Absence of postoperative complications Early radio-induced epidermis grade ≥2 (CTCAE v4.0) persistent at inclusion Chest circumference <120 cm and Cup <E, Absence of breast reconstructive surgery, Signature of informed consent, Affiliation to a social security scheme for French patients. Group B Patients over 18 years old, Breast cancer (adenocarcinoma in situ or invasive) Non-metastatic disease Radiotherapy after conservative surgery with irradiation of the breast alone and complement on the operating bed (optional), completed two to six months ago Absence of postoperative complications Early grade 0-1 radiation-induced epidermis (CTCAE v4.0) at inclusion Chest circumference <120 cm and Cup <E, Absence of breast reconstructive surgery, Signature of informed consent, Affiliation to a social security scheme for French patients. Groups C, D Patients included in the SPLICIRAD study who have formulated their agreement for the use of supernumerary samples at the time of inclusion: 10 patients with late pathologic radio-induced fibrosis (more than 6 months after the end of radiotherapy), grade CTCAE v4.0 ≥ 3 vs. 10 patients without late pathological radio-induced fibrosis of grade CTCAE v4.0 ≤ 1 (follow-up after RT ≥4 years) Group E Patients over 18 who have given their consent to the Blood Establishment for the use of their samples for research purposes. Non-inclusion criteria for groups A, B, C, D: Systemic inflammatory disease associated with individual radiosensitivity Dermatological pathology in the breast Radiotherapy having delivered an overdose> 107% of the prescribed dose in at least 10% of the PTV Diabetes Active smoking Chronic systemic anti-inflammatory therapy, immunotherapy, immunosuppressants, anti-TNF

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The are 5 groups of patients: Group A and B : cohort prospective Groups C and D : cohort retrospective Group E : control group, samples from French blood establishment For groups A and B, the only intervention consists in a blood sample.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A<br>Patients with early grade ≥2 radio-induced epidermis Intervention : blood sample | Biological: Blood sampling<br>* Blood sample of 7 mL whole venous blood in an EDTA citrate tube (4.5 mL) and a PAXgene Blood RNA tube (2.5 mL).<br>|
| Other: Group B<br>Patients with early grade 0-1 radiation-induced epidermis Intervention : blood sample | Biological: Blood sampling<br>* Blood sample of 7 mL whole venous blood in an EDTA citrate tube (4.5 mL) and a PAXgene Blood RNA tube (2.5 mL).<br>|
| No Intervention: Group C<br>Patients with late pathologic radio-induced fibrosis (more than 6 months after the end of radiotherapy), grade CTCAE v4.0 ≥ 3 No intervention : Blood sample already collected from another study and patients agree to use their blood sample for another research | |
| No Intervention: Group D<br>Patients without late pathologic radio-induced fibrosis of grade CTCAE v4.0 ≤ 1 (follow-up after RT ≥4 years) No intervention : Blood sample already collected from another study and patients agree to use their blood sample for another research | |
| No Intervention: Group E<br>Control group : patients over 18 who have given their consent to the Blood Establishment for the use of their samples for research purposes. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coorelate the amount of circulating TREM1 with the presence or absence of early persistent radiation-induced epidermis. | Correlate the amount of circulating TREM1 with the presence or absence of early persistent radiation-induced epidermis. | after recruitment of all samples, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate the amount of circulating TREM1 with the presence or absence of late radio-induced fibrosis / atrophy | Correlate the amount of circulating TREM1 with the presence or absence of late radio-induced fibrosis / atrophy | after recruitment of all samples, an average of 2 years | 
| Intrinsic characteristics of the TREM1 blood assay in ELISA technique | Intrinsic characteristics of the TREM1 blood assay in ELISA technique | after recruitment of all samples, an average of 2 years | 
| correlate TREM-1 expression with circulating markers of inflammation such as IL-6, CRP, and fibrosis such as TGF-beta, IL-1beta, TNF-alpha | correlate TREM-1 expression with circulating markers of inflammation such as IL-6, CRP, and fibrosis such as TGF-beta, IL-1beta, TNF-alpha | after recruitment of all samples, an average of 2 years |