Modifications of Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative BC (MIMOSA)

December 22, 2022 updated by: Institut Claudius Regaud

Study of the Modifications of the Immune Microenvironment Induced by Neoadjuvant Chemotherapy in Triple-negative Breast Cancers

The prescription of neoadjuvant chemotherapy becomes a standard in women with HER2-positive or triple-negative breast cancer and allows a complete histological response (pCR) which represents a prognostic factor for survival. . The problem for patients who are not pCR is that they are currently receiving non-personalized adjuvant systemic treatment.

The identification of biomarkers present in the residual disease would be a criterion to guide the choice of post-neoadjuvant adjuvant systemic treatment, in order to personalize it.

At the present time, there is no published study describing extensively the immune micro-environment (ME) in breast cancer, whether before or after chemotherapy, nor its modification induced by chemotherapy.

The team therefore propose to study in a retrospective and monocentric series, the modifications of the immune ME induced by a "standard" neo-adjuvant chemotherapy in patients with triple-negative CS, whether they are in complete histological response or not (n = twice 50).

The main objective of this project is to describe the changes in the immune ME of triple-negative breast cancers induced by neoadjuvant chemotherapy for all patients (in pCR or not):

  • Quantification of TILs and subtypes of TILs (CD4 and CD8)
  • Expression of the three immune checkpoints that are PDL1, TIM3 and LAG3
  • Describe the organization of the immune system (immunostaining on the same slide of the PDL1, TIM3 and LAG3 immune checkpoints)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Retrospective and monocentric translational study carried out on patients treated at the IUCT-Oncopole by neoadjuvant chemotherapy (sequential treatment FEC100 or EC100 then taxane, paclitaxel weekly for the most part) for a triple-negative CS between 2012 and 2018.

We have the microbiopsy of the primary tumor preserved in FFPE and the operating room preserved in FFPE.

We have all the clinical data for the diagnosis and monitoring of these patients, already entered into a database.

The search for a BRCA germline mutation is available in most patients if indicated for an oncogenetic consultation.

biomarkers analysis :

  • TILS account according to Salgado et al. before and after neoadjuvant chemotherapy
  • IHC CK5-6 and EGFR then RA if the first two are negative to characterize triple negative tumors in "basal-like" and "non-basal-like"
  • IHC CD3 (labeling of T lymphocytes)
  • IHC CD4, CD8 and FOXP3 before and after neoadjuvant chemotherapy
  • PDL1, TIM3 and LAG3 multiplex IHC before and after neoadjuvant chemotherapy
  • Labeling of tumor cells: AE1 / AE3
  • Use of markings for exploratory analyzes: CD68 (macrophages), CD39 (marker of lymphocyte exhaust

Study Type

Observational

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Toulouse, France, 31059
        • Institut Claudius Regaud

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

100 samples

Description

Inclusion Criteria:

  • Samples from triple negative BC patients, patients treated by neoadjuvant chemotherapy ( FEC or EC than taxanes) Patients consent to use their samples.

Exclusion Criteria:

  • Samples not available before or after neoadjuvant chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identify Change of immune ME by TILS quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients
Time Frame: 12 months
TILS ans substype quantification
12 months
Identify Change of immune ME by PDL1 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients
Time Frame: 12 months
expression of PDL1,
12 months
Identify Change of immune ME by TIM3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients
Time Frame: 12 months
expression of TIM3
12 months
Identify Change of immune ME by LAG3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients
Time Frame: 12 months
LAG3 expression
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare change ofTILs quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like
Time Frame: 12 months
Quantification of TILs and subtypes TILs;
12 months
Compare change of PDL1 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like
Time Frame: 12 months
expression of PDL1
12 months
Compare change of TIM3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like
Time Frame: 12 months
expression of TIM3
12 months
Compare change of LAG3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for pCR patients and those not pCR and for subtype basal-like or not basal-like
Time Frame: 12 months
expression of LAG3; organization of immune system
12 months
determination of predictive factors of TILs quantification for response to neoadjuvant chemotherapy and disease free survival
Time Frame: 12 months
Correlation between TILs and TILs substypes quantification (on microbiopsy) and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.
12 months
determination of predictive factors of PDL1 expression for response to neoadjuvant chemotherapy and disease free survival
Time Frame: 12 months
Correlation between PDL1 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.
12 months
determination of predictive factors of TIM3 for response to neoadjuvant chemotherapy and disease free survival
Time Frame: 12 months
Correlation between TIM3 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.
12 months
determination of predictive factors of LAG3 for response to neoadjuvant chemotherapy and disease free survival
Time Frame: 12 months
Correlation between LAG3 expression on microbiopsy and the histological response after neoadjuvant chemotherapy (pCR versus non pCR): determination of predictive factors for response to chemotherapy.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Claudius Regaud

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2020

Primary Completion (Actual)

December 15, 2020

Study Completion (Actual)

January 31, 2021

Study Registration Dates

First Submitted

April 20, 2020

First Submitted That Met QC Criteria

April 27, 2020

First Posted (Actual)

April 29, 2020

Study Record Updates

Last Update Posted (Actual)

December 23, 2022

Last Update Submitted That Met QC Criteria

December 22, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19HLSEIN02

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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