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NCT Number: NCT04368468

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

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)

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Key information

Conditions

Triple Negative Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases Triple Negative Breast Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Institut claudius regaud

Toulouse, 31059, France

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

biomarker evolution

Other

analysis of a list of biomarkers on triple negative breast tumors samples before and after neoadjuvant therapy

Other names: triple negative breast cancer biomarker evolution

Primary outcomes

  1. 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

  2. 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,

  3. 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

  4. 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

Secondary outcomes

  1. 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;

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

Sponsors and collaborators

Lead sponsor

Institut Claudius Regaud

Other

Registry information

Official study title

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

Acronym: MIMOSA

Important dates

Study start
2020
Primary completion
2020
Study completion
2021
First posted
Apr 29, 2020
Registry last updated
Dec 23, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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