Clinical trial NCT01513408: Relevance of T Lymphocytes Tumor Infiltrates CD8 and Foxp3 as Immune Prognostic Biomarker in Breast Cancer Treated by Neo Adjuvant Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
CD8+
Foxp3
neoadjuvant chemotherapy
Lead sponsor: Centre Georges Francois Leclerc
Sponsor class: OTHER
First posted: 2012-01-20
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Overall survival
timeFrame: From date of inclusion up to the end of follow-up period : december 2014 (anticipated)
Secondary outcomes:
measure: Recurrence-free survival
timeFrame: From inclusion up to the end of follow up period: december 2014
measure: Pathological complete response
timeFrame: After surgery
measure: PathIm score (pathological-immunological)
timeFrame: From inclusion up to the end of surgery for all patients: december 2014 (anticipated)
Other outcomes:
Locations:
city: Dijon
country: France
facility: CGFL
Study officials:
affiliation: Centre Georges Francois Leclerc
name: Sylvain LADOIRE, MD
role: PRINCIPAL_INVESTIGATOR
References: