Pilot Study of the Predictive Value of TREM1 Expression and Activation in Inflammation and Radio-induced Mammary Fibrosis (TREM-1)

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.

Study Overview

• Status: Recruiting
• Conditions: Fibrosis; Breast Cancer; Radiation Toxicity
• Intervention / Treatment: Biological: Blood sampling

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Metz, France
    • Recruiting
    • Centre Hospitalier de Metz Thionville
    • Contact: Claire Gamelon - Benichou, MD
  • Nancy, France
    • Recruiting
    • Institut de cancerologie de Lorraine
• Luxembourg
  • SUD
    • Esch-sur-Alzette, SUD, Luxembourg, 4240
      • Recruiting
      • Centre Francois Baclesse
      • Contact: Guillaume Vogin, MD PhD
      • Contact: Charlotte Lieunard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Group A

1. Patients over 18 years old,
2. Breast cancer (adenocarcinoma in situ or invasive)
3. Non-metastatic disease
4. Radiotherapy after conservative surgery with irradiation of the breast alone and complement on the operating bed (optional) completed two to six months ago
5. Absence of postoperative complications
6. Early radio-induced epidermis grade ≥2 (CTCAE v4.0) persistent at inclusion
7. Chest circumference <120 cm and Cup <E,
8. Absence of breast reconstructive surgery,
9. Signature of informed consent,
10. Affiliation to a social security scheme for French patients.

Group B

1. Patients over 18 years old,
2. Breast cancer (adenocarcinoma in situ or invasive)
3. Non-metastatic disease
4. Radiotherapy after conservative surgery with irradiation of the breast alone and complement on the operating bed (optional), completed two to six months ago
5. Absence of postoperative complications
6. Early grade 0-1 radiation-induced epidermis (CTCAE v4.0) at inclusion
7. Chest circumference <120 cm and Cup <E,
8. Absence of breast reconstructive surgery,
9. Signature of informed consent,
10. 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:

1. Systemic inflammatory disease associated with individual radiosensitivity
2. Dermatological pathology in the breast
3. Radiotherapy having delivered an overdose> 107% of the prescribed dose in at least 10% of the PTV
4. Diabetes
5. Active smoking
6. Chronic systemic anti-inflammatory therapy, immunotherapy, immunosuppressants, anti-TNF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A; Patients with early grade ≥2 radio-induced epidermis Intervention : blood sample	Biological: Blood sampling; 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).
Other: Group B; Patients with early grade 0-1 radiation-induced epidermis Intervention : blood sample	Biological: Blood sampling; 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).
No Intervention: Group C; 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; 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; 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?

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

Collaborators and Investigators

• Sponsor: Centre Francois Baclesse, Luxembourg
• Collaborators: Inotrem

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: June 17, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): July 2, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Inflammation
• Other Study ID Numbers: TREM-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No