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Breast CancerTMEM-MRINCT03694756

TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer

A study testing TMEM-MRI and FNA in people with Breast Cancer, run by Montefiore Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer - Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
TMEM-MRI and FNA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
1 siteUnited States
Study dates
12 Dec 2018to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For pre-pilot phase (MRI sequence development):
  • o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)
  • For pilot phase Cohort A:
  • o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).
  • For pilot phase Cohort B:
  • Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
Show all 25Show fewer
  • No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
  • For pilot phase Cohort C:
  • Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
  • Residual palpable mass > 1 cm in largest diameter after neoadjuvant therapy.
  • Candidate for breast MRI before definitive surgery.
  • Tumor size/breast mass should be > 1 cm in largest diameter (radiologically).
  • Multifocal disease is allowed, as long as patients meet all eligibility criteria.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Willingness to undergo a "research breast MRI".
  • Patient must be able to undergo MRI with gadolinium enhancement.
  • No history of untreatable claustrophobia.
  • No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
  • No history of sickle cell disease.
  • No contraindication to intravenous contrast administration.
  • No known allergy-like reaction to gadolinium
  • No known or suspected renal impairment. Glomerular Filtration Rate (GFR) should be greater than 30 mL/min/1.73 m2.
  • Weight less than or equal to the MRI table limit.
  • Ability to understand and willingness to sign a written informed consent.

Who cannot join

  • Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
  • No breast prosthetic implants (silicone or saline) are allowed.
  • Use of any investigational agent within 30 days of starting study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
  • Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jesus Anampa, MD, MS contact

7184058505

janampa@montefiore.org

United States1 site, 1 recruiting

  • Montefiore Medical Center

    The Bronx, New York, 10461

    Jesus D Anampa, MD,MS, 718-405-8505, janampa@montefiore.org

    Karen Fehn, RN, 7184058505, kfehn@montefiore.org

    Recruiting

Other trials in United States

About this study

Official title: TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer - Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI).

Read the detailed description

The primary objective of this study is to develop a magnetic resonance imaging (MRI) based method for assessing TMEM-mediated permeability associated with cancer cell dissemination in breast cancer patients. TMEM-MRI has the ability to detect tumor areas with more leakiness (perfusion), where cancer cells enter blood vessels to travel to other sites. This novel TMEM-MRI has potential to be used in clinical practice to identify tumors with high leakiness that might have higher chances to recur after breast cancer treatment. In addition, TMEM-MRI can potentially be used to assess response to preoperative treatments (chemotherapy, hormonal therapy) over time.

In a prior study, it was found that patients with high TMEM doorway score, compared to patients with mid/low TMEM doorway score, in their residual disease after neoadjuvant therapy, had worse distant relapse-free survival (p = 0.008). These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development of the proposed TMEM MRI in humans, the tumor microenvironment is naïve to treatment. However, neoadjuvant therapy may affect the tumor microenvironment which could affect vascular anatomy - a key component of the TMEM MRI algorithm. Therefore, the study team aims to assess the correlation between TMEM doorway density and TMEM MRI activity after neoadjuvant therapy (Pilot Cohort C).

Conditions
Breast Cancer
Being tested
TMEM-MRI, FNA
Keywords
TMEM;, Magnetic resonance imaging (MRI)
Medical subject headings
Breast Neoplasms

What participants receive

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

  • TMEM-MRIDevice

    TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.

  • FNAProcedure or surgery

    FNA: The patients who are recruited prior to biopsy (Cohort A) will have had TMEM-MRI performed prior to biopsy. They will then present to radiology for ultrasound-guided core biopsy of the breast mass. FNA will be performed during this procedure. The FNA will be performed after local anesthetic is administered but prior to insertion of the core biopsy needle. FNA will be performed by the radiologist under direct sonographic visualization of the mass. Five passes will be obtained with a 25-gauge needle. The FNA material will be expelled into 1.5 ml Eppendorf tube containing phosphate buffered saline with Ethylenediaminetetraacetic acid (EDTA).

Study groups in NCT03694756
Study groupRoleWhat they receive
Pre-biopsy patients (Cohort A)OtherPatients identified by radiologist at the time of diagnostic evaluation and TMEM-MRI scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional fine-needle aspiration (FNA) preceding the core biopsy). After the breast biopsy confirms the suspected diagnosis of invasive breast carcinoma, the patient will be referred to breast surgery and a treatment plan devised per National Comprehensive Cancer Network/American Society of Clinical Oncology (NCCN/ASCO) guidelines. No patients were enrolled into this arm/group and Cohort A has been removed by protocol amendment. This was intended to be a cohort for patients before breast biopsy in the event the biopsy procedure created a hematoma which would, in turn, affect measurement of TMEM-MRI activity. Since this effect was not observed in the first set of patients enrolled, Cohort A was removed from the study and only patients post-breast biopsy were enrolled (Cohort B).
Receives: Device: TMEM-MRI; Procedure: FNA
Post-biopsy patients (Cohort B)OtherPatients after breast biopsy. Once consent is obtained, patients will undergo TMEM-MRI. The patients will undergo definitive breast surgery and will receive adjuvant treatments as per NCCN/ASCO guidelines. TMEM density, MenaCalc and MenaINV will be evaluated in final surgical specimen. Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV.
Receives: Device: TMEM-MRI
Post-neoadjuvant therapy patients (Cohort C)OtherPatients status post neoadjuvant therapy. Patients who received neoadjuvant will be enrolled into Cohort C to understand the correlation between TMEM MRI activity and TMEM doorway density following after neoadjuvant chemotherapy. Only patients with residual palpable mass on physical exam will be included (≥ 1cm). Patients will undergo TMEM-MRI after neoadjuvant therapy is completed. Patients will also have CTCs and circulating tumor DNA (ctDNA) measured on the same day of TMEM-MRI (+/- 3 days). TMEM density, MenaCalc and MenaINV will be evaluated in breast surgical specimen (after pre-operative therapy). Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV after pre-operative therapy.
Receives: Device: TMEM-MRI

What is being measured

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

  1. Tumor permeability assessed by TMEM-MRI

    Tumor permeability will be assessed by TMEM-MRI, and is defined as a number of Uth units (the number of tumor voxels with permeability density above threshold divided by the number of all tumor voxels) that will be obtained from the permeability map and TMEM-MRI algorithm.

    Measured: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery

Secondary outcomes (4)

  1. TMEM density in breast cancer patients

    TMEM density is defined as the number of TMEM units visualized by triple immunohistochemistry in 10 high power fields (40X). TMEM density will be measured with a fully automated and scalable clinical assay for identification and enumeration of TMEM utilizing digital pathology methods coupled with image analysis

    Measured: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes

  2. MenaCalc

    MenaCalc is calculated by subtracting the Z-score value of Mena11a from the Z-score value of pan-Mena, obtained by quantitative immunohistochemistry in formalin-fixed paraffin-embedded breast tumor specimens. MenaCalc can also be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in cancer cells obtained by FNA

    Measured: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes

  3. MenaInv

    MenaInv is calculated as pixel intensity obtained by quantitative immunofluorescence per area of formalin-fixed paraffin-embedded tumor tissue. MenaINV can also be measured by qRT-PCR in cancer cells obtained by FNA

    Measured: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes

  4. Circulating Tumor Cells (CTCs)

    CTCs will detected and enumerated from peripheral blood samples using EPIC sciences or RareCyte platform. Patients will undergo venipuncture to obtain specimen for CTC assays. Specimens will be shipped to EPIC sciences (using CTC liquid biopsy blood collection kit) or the University of Southern California (using RareCyte collection kit) to be processed and analyzed as per respective protocols. CTCs will be measured +/- 3 days of TMEM-MRI. Group mean results in number of cells/mL of peripheral blood will be reported for patients in pilot phase Cohort B and pilot phase Cohort C.

    Measured: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery

Timeline

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

  1. First posted3 Oct 2018
  2. Study start12 Dec 2018
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Patients were originally intended to be enrolled in 2 cohorts (A and B), based on breast biopsy status; however, the study design was changed following Protocol Amendment.
Masking
None (open label)
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03694756
Sponsor's protocol ID
2018-9529
Acronym
TMEM-MRI
Status last verified
Nov 2025
First submitted
28 Sep 2018
Last updated
10 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

    PubMed 21296855

  • Hellman, S. and J.R. Harris, Natural history of breast cancer, in Diseases of the Breast., J.R. eds Harris, Lippman, M. E., Morrow, M. & Osborne, C. K., Editor. 2000, Lippincott Williams & Wilkins: Philadelphia. p. 407-23.

  • Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. doi: 10.1038/nrc1670.

    PubMed 16056258

  • Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009 Nov 25;139(5):871-90. doi: 10.1016/j.cell.2009.11.007.

    PubMed 19945376

  • Fidler IJ, Poste G. The "seed and soil" hypothesis revisited. Lancet Oncol. 2008 Aug;9(8):808. doi: 10.1016/S1470-2045(08)70201-8. No abstract available.

    PubMed 18672217

  • Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009 Jun;119(6):1420-8. doi: 10.1172/JCI39104.

    PubMed 19487818

  • Warzecha CC, Carstens RP. Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT). Semin Cancer Biol. 2012 Oct;22(5-6):417-27. doi: 10.1016/j.semcancer.2012.04.003. Epub 2012 Apr 23.

    PubMed 22548723

  • Ellis JD, Barrios-Rodiles M, Colak R, Irimia M, Kim T, Calarco JA, Wang X, Pan Q, O'Hanlon D, Kim PM, Wrana JL, Blencowe BJ. Tissue-specific alternative splicing remodels protein-protein interaction networks. Mol Cell. 2012 Jun 29;46(6):884-92. doi: 10.1016/j.molcel.2012.05.037.

    PubMed 22749401

  • Gertler F, Condeelis J. Metastasis: tumor cells becoming MENAcing. Trends Cell Biol. 2011 Feb;21(2):81-90. doi: 10.1016/j.tcb.2010.10.001. Epub 2010 Nov 9.

    PubMed 21071226

  • Shapiro IM, Cheng AW, Flytzanis NC, Balsamo M, Condeelis JS, Oktay MH, Burge CB, Gertler FB. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 2011 Aug;7(8):e1002218. doi: 10.1371/journal.pgen.1002218. Epub 2011 Aug 18.

    PubMed 21876675

  • Agarwal S, Gertler FB, Balsamo M, Condeelis JS, Camp RL, Xue X, Lin J, Rohan TE, Rimm DL. Quantitative assessment of invasive mena isoforms (Menacalc) as an independent prognostic marker in breast cancer. Breast Cancer Res. 2012 Sep 12;14(5):R124. doi: 10.1186/bcr3318.

    PubMed 22971274

  • Forse CL, Agarwal S, Pinnaduwage D, Gertler F, Condeelis JS, Lin J, Xue X, Johung K, Mulligan AM, Rohan TE, Bull SB, Andrulis IL. Menacalc, a quantitative method of metastasis assessment, as a prognostic marker for axillary node-negative breast cancer. BMC Cancer. 2015 Jun 27;15:483. doi: 10.1186/s12885-015-1468-6.

    PubMed 26112005

  • Di Modugno F, Bronzi G, Scanlan MJ, Del Bello D, Cascioli S, Venturo I, Botti C, Nicotra MR, Mottolese M, Natali PG, Santoni A, Jager E, Nistico P. Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T-cell immune response. Int J Cancer. 2004 May 10;109(6):909-18. doi: 10.1002/ijc.20094.

    PubMed 15027125

  • Goswami S, Philippar U, Sun D, Patsialou A, Avraham J, Wang W, Di Modugno F, Nistico P, Gertler FB, Condeelis JS. Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo. Clin Exp Metastasis. 2009;26(2):153-9. doi: 10.1007/s10585-008-9225-8. Epub 2008 Nov 5.

    PubMed 18985426

  • Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim HD, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Lauffenburger DA, Sahai E, Condeelis JS, Gertler FB. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell. 2008 Dec;15(6):813-28. doi: 10.1016/j.devcel.2008.09.003.

    PubMed 19081071

Questions about this trial

What is this clinical trial studying?

A study testing TMEM-MRI and FNA in people with Breast Cancer, run by Montefiore Medical Center at 1 site in United States.

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 25 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 10 Nov 2025. 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 United States. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Jesus Anampa, MD, MS (7184058505, janampa@montefiore.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor permeability assessed by TMEM-MRI (time frame: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery). 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 NCT03694756, which also lists 34 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 10 Nov 2025.

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