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

NCT01513408 | Unknown

• 1 other identifier: 2011-1SLa-01
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

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

Keywords

breast cancer; CD8+; Foxp3; neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival is defined as the time from inclusion date to death from any cause, or to date of last follow-up, if death does not occur.

  From date of inclusion up to the end of follow-up period : december 2014 (anticipated)

Secondary Outcomes (3)

• Recurrence-free survival

  From inclusion up to the end of follow up period: december 2014

• Pathological complete response

  After surgery

• PathIm score (pathological-immunological)

  From inclusion up to the end of surgery for all patients: december 2014 (anticipated)

Study Arms (1)

CD8/Foxp3

EXPERIMENTAL

patient suffering from non-metastatic breast cancer

Other: immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio

Interventions

immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio 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.

CD8/Foxp3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Social security coverage
• Age between 18 and 80 years
• Histologically proven breast cancer, regardless of histological type or molecular subtype (triple negative, hormone-receptor positive, HER2+++), including inflammatory forms
• Localised breast cancer with or without axillary or subclavicular lymph node involvement
• 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)
• Treatment by neoadjuvant chemotherapy (treatment protocol at physician's discretion)
• Patient amenable to receiving adjuvant therapy (chemotherapy, radiotherapy, hormone therapy, targeted therapy)
• Breast surgery (breast-sparing or not) planned after neoadjuvant chemotherapy

You may not qualify if:

• Metastatic breast cancer
• Neoadjuvant radiotherapy
• Patient not amenable to surgery
• Ongoing therapy for any other type of cancer
• Legal incapacity (incarceration or persons under legal guardianship)
• Patient unable to sign the informed consent or unable to attend medical follow-up for geographical, social or mental reasons.

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead

Study Sites (1)

CGFL

Dijon, 21079, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sylvain LADOIRE, MD

  Centre Georges Francois Leclerc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 20, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2025
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

FR (1)