Relevance of T Lymphocytes Tumor Infiltrates CD8 and Foxp3 as Immune Prognostic Biomarker in Breast Cancer Treated by Neo Adjuvant Chemotherapy

NCT ID: NCT01513408

Last Updated: 2023-10-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2025-10-31

Brief Summary

Neoadjuvant chemotherapy is standard therapy for the management of localised breast cancer, and makes it possible to evaluate tumour response. Achieving pathological complete response (pCR) after chemotherapy is the most important prognostic factor for these patients. However, patients with pCR can suffer relapse. In parallel, long-term prognosis of patients who do not achieve pCR is poorly documented, and no specific prognostic factors have been clearly identified.Preclinical and clinical studies argue for an immunogenic role of some chemotherapy regimens, such as anthracyclines, taxanes or trastuzumab. By facilitating recruitment of CD8 T-lymphocytes in the tumour bed, these agents could favourably influence antitumour immune response, partially contributing to efficacy. Conversely, tumours can promote accumulation of regulatory T-lymphocytes expressing Foxp3, thus evading anti-tumour immune response, and increased numbers of regulatory T-cells are associated with less favourable prognosis in breast cancer patients. We have previously shown that a high number of CD8 T-cells associated with low Foxp3 infiltration, as quantified by immunohistochemistry on surgical specimens, is associated with better response and better survival in breast cancer patients, independently of whether pCR was achieved, the type of chemotherapy used, and the type of breast cancer. Therefore, we propose to validate in a prospective study this immunological prognostic marker in a large cohort of patients treated with neoadjuvant chemotherapy.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

CD8/Foxp3

patient suffering from non-metastatic breast cancer

Group Type: EXPERIMENTAL

immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio

Intervention Type: OTHER

For each patients included the study, a tumour block from the initial biopsy, as well as a representative block of residual tumour (area of complete tumoral regression, area of partial tumoral regression or area of unmodified residual tumour) will be chosen by the initial pathologist in each investigating centre. Once the pathologist has verified the concordance between the images observed on the blocks sent from the investigating centres, and the associated pathology reports, immunohistochemical analysis will be performed on the slides prepared from each block.

Interventions

immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio

For each patients included the study, a tumour block from the initial biopsy, as well as a representative block of residual tumour (area of complete tumoral regression, area of partial tumoral regression or area of unmodified residual tumour) will be chosen by the initial pathologist in each investigating centre. Once the pathologist has verified the concordance between the images observed on the blocks sent from the investigating centres, and the associated pathology reports, immunohistochemical analysis will be performed on the slides prepared from each block.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent

2. Social security coverage

3. Age between 18 and 80 years

4. Histologically proven breast cancer, regardless of histological type or molecular subtype (triple negative, hormone-receptor positive, HER2+++), including inflammatory forms

5. Localised breast cancer with or without axillary or subclavicular lymph node involvement

6. Absence of bone or visceral metastasis on further evaluation (bone scintigraphy, chest X-ray, abdominal echocardiography or CT scan of the thorax, abdomen and pelvic area)

7. Treatment by neoadjuvant chemotherapy (treatment protocol at physician's discretion)

8. Patient amenable to receiving adjuvant therapy (chemotherapy, radiotherapy, hormone therapy, targeted therapy)

9. Breast surgery (breast-sparing or not) planned after neoadjuvant chemotherapy

Exclusion Criteria

1. Metastatic breast cancer

2. Neoadjuvant radiotherapy

3. Patient not amenable to surgery

4. Ongoing therapy for any other type of cancer

5. Legal incapacity (incarceration or persons under legal guardianship)

6. Patient unable to sign the informed consent or unable to attend medical follow-up for geographical, social or mental reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Georges Francois Leclerc

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvain LADOIRE, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Georges Francois Leclerc

Locations

CGFL

Dijon, , France

Countries

France

Other Identifiers

2011-1SLa-01

Identifier Type: -

Identifier Source: org_study_id