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Triple Negative Breast CancerMIMOSANCT04368468

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

An observational study of Triple Negative Breast Cancer, run by Institut Claudius Regaud at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. . Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
biomarker evolution
How many people
100 participants
Where
1 siteFrance
Study dates
15 Jun 2020to 31 Jan 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Study population: 100 samples

Who may be able to join

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

Who cannot join

  • Samples not available before or after neoadjuvant chemotherapy

Trial locations and contacts

1 site in 1 country.

France1 site

  • Institut claudius regaud

    Toulouse, 31059

Other trials in France

About this study

Official title: 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.

Read more

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)
Read the 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
Being tested
biomarker evolution
Keywords
post neo adjuvant therapy, immune micro environment, biomerker chacterization
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • biomarker evolutionOther

    Also called triple negative breast cancer biomarker evolution

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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Identify Change of immune ME by TILS quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients

    TILS ans substype quantification

    Measured: 12 months

  2. Identify Change of immune ME by PDL1 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients

    expression of PDL1,

    Measured: 12 months

  3. Identify Change of immune ME by TIM3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients

    expression of TIM3

    Measured: 12 months

  4. Identify Change of immune ME by LAG3 expression of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients

    LAG3 expression

    Measured: 12 months

Secondary outcomes (8)

  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

    Quantification of TILs and subtypes TILs;

    Measured: 12 months

  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

    expression of PDL1

    Measured: 12 months

  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

    expression of TIM3

    Measured: 12 months

  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

    expression of LAG3; organization of immune system

    Measured: 12 months

  5. determination of predictive factors of TILs quantification for response to neoadjuvant chemotherapy and disease free survival

    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.

    Measured: 12 months

  6. determination of predictive factors of PDL1 expression for response to neoadjuvant chemotherapy and disease free survival

    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.

    Measured: 12 months

  7. determination of predictive factors of TIM3 for response to neoadjuvant chemotherapy and disease free survival

    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.

    Measured: 12 months

  8. determination of predictive factors of LAG3 for response to neoadjuvant chemotherapy and disease free survival

    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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2020
  2. Study start15 Jun 2020
  3. Primary completion15 Dec 2020
  4. Study completion31 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04368468
Sponsor's protocol ID
19HLSEIN02
Acronym
MIMOSA
Status last verified
Dec 2022
First submitted
20 Apr 2020
Last updated
23 Dec 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pusztai L, Foldi J, Dhawan A, DiGiovanna MP, Mamounas EP. Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers. Lancet Oncol. 2019 Jul;20(7):e390-e396. doi: 10.1016/S1470-2045(19)30158-5.

    PubMed 31267973

  • Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. doi: 10.1200/JCO.2007.10.6823. Epub 2007 Sep 4.

    PubMed 17785706

  • Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.

    PubMed 24529560

  • von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wulfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. doi: 10.1056/NEJMoa1814017. Epub 2018 Dec 5.

    PubMed 30516102

  • Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147-2159. doi: 10.1056/NEJMoa1612645.

    PubMed 28564564

  • Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, Martino S, Wang M, Jones VE, Saphner TJ, Wolff AC, Wood WC, Davidson NE, Sledge GW, Sparano JA, Badve SS. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014 Sep 20;32(27):2959-66. doi: 10.1200/JCO.2013.55.0491.

    PubMed 25071121

  • Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, Rouas G, Francis P, Crown JP, Hitre E, de Azambuja E, Quinaux E, Di Leo A, Michiels S, Piccart MJ, Sotiriou C. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol. 2013 Mar 1;31(7):860-7. doi: 10.1200/JCO.2011.41.0902. Epub 2013 Jan 22.

    PubMed 23341518

  • Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, Joensuu H, Dieci MV, Badve S, Demaria S, Gray R, Munzone E, Lemonnier J, Sotiriou C, Piccart MJ, Kellokumpu-Lehtinen PL, Vingiani A, Gray K, Andre F, Denkert C, Salgado R, Michiels S. Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers. J Clin Oncol. 2019 Mar 1;37(7):559-569. doi: 10.1200/JCO.18.01010. Epub 2019 Jan 16.

    PubMed 30650045

  • DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009 Aug 4;16(2):91-102. doi: 10.1016/j.ccr.2009.06.018.

    PubMed 19647220

  • Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011 May 20;29(15):1949-55. doi: 10.1200/JCO.2010.30.5037. Epub 2011 Apr 11.

    PubMed 21483002

  • Mahmoud SM, Lee AH, Paish EC, Macmillan RD, Ellis IO, Green AR. The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat. 2012 Apr;132(2):545-53. doi: 10.1007/s10549-011-1620-1. Epub 2011 Jun 14.

    PubMed 21671016

  • Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, de Wind A, Ravoet M, Le Buanec H, Sibille C, Manfouo-Foutsop G, Veys I, Haibe-Kains B, Singhal SK, Michiels S, Rothe F, Salgado R, Duvillier H, Ignatiadis M, Desmedt C, Bron D, Larsimont D, Piccart M, Sotiriou C, Willard-Gallo K. CD4(+) follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. 2013 Jul;123(7):2873-92. doi: 10.1172/JCI67428. Epub 2013 Jun 17.

    PubMed 23778140

  • Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J, Castellano R, Goncalves A, Andre P, Romagne F, Thibault G, Viens P, Birnbaum D, Bertucci F, Moretta A, Olive D. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest. 2011 Sep;121(9):3609-22. doi: 10.1172/JCI45816. Epub 2011 Aug 15.

    PubMed 21841316

  • Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006 Dec 1;24(34):5373-80. doi: 10.1200/JCO.2006.05.9584.

    PubMed 17135638

  • Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Lee AH, Ellis IO, Green AR. An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res Treat. 2011 May;127(1):99-108. doi: 10.1007/s10549-010-0987-8. Epub 2010 Jun 17.

    PubMed 20556505

Questions about this trial

What is this clinical trial studying?

An observational study of Triple Negative Breast Cancer, run by Institut Claudius Regaud at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Identify Change of immune ME by TILS quantification of triple-negative breast cancer induced by neoadjuvant chemotherapy for all patients (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04368468, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2022.

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