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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01513408
Recruitment Status : Completed
First Posted : January 20, 2012
Last Update Posted : October 18, 2017
Information provided by (Responsible Party):
Centre Georges Francois Leclerc

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Other: immunohistochemical detection of lymphocytes T CD8+/Foxp3 ratio Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 500 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prospective Study of the Relevance of T Lymphocytes Tumor Infiltrates CD8 and Foxp3 as a New imMUne Prognostic Biomarker in Breast Cancer Treated by NEOadjuvant Chemotherapy
Actual Study Start Date : May 2012
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: CD8/Foxp3
patient suffering from non-metastatic breast cancer
Other: 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.

Primary Outcome Measures :
  1. Overall survival [ Time Frame: From date of inclusion up to the end of follow-up period : december 2014 (anticipated) ]
    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.

Secondary Outcome Measures :
  1. Recurrence-free survival [ Time Frame: From inclusion up to the end of follow up period: december 2014 ]
    Recurrence-free survival is defined as the time interval from the date of surgery to the date of first recurrence (loco-regional or metastatic) or to death (all causes). Patients alive without recurrence will be censored on the date of last follow-up.

  2. Pathological complete response [ Time Frame: After surgery ]
    Pathological complete response on the surgically resected specimen is defined as the absence of any evidence of invasive carcinoma in the breast or dissected axillary lymph nodes.

  3. PathIm score (pathological-immunological) [ Time Frame: From inclusion up to the end of surgery for all patients: december 2014 (anticipated) ]
    PathIm score (pathological-immunological)from 0 to 2, defining three patient groups with different prognoses (0 = good prognosis; 1 = intermediate prognosis; 2 = unfavourable prognosis), and defined as the sum of the pathology information regarding the extent of residual tumour according to the pAJCC score(pAJCC stage≤IIA = 0; pAJCC stage>IIA = 1), and the immunological information from the CD8/Foxp3 ratio (high CD8 AND low Foxp3 infiltration = 0, all other situations = 1)

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01513408

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Dijon, France, 21079
Sponsors and Collaborators
Centre Georges Francois Leclerc
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Principal Investigator: Sylvain LADOIRE, MD Centre Georges Francois Leclerc

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Responsible Party: Centre Georges Francois Leclerc Identifier: NCT01513408     History of Changes
Other Study ID Numbers: 2011-1SLa-01
First Posted: January 20, 2012    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: June 2017
Keywords provided by Centre Georges Francois Leclerc:
breast cancer
neoadjuvant chemotherapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases