TMEM-MRI Imaging for Breast Cancer

(TMEM-MRI Trial)

Recruiting at 1 trial location

Overseen By Jesus Anampa, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Montefiore Medical Center

Must not be taking: Investigational agents

Disqualifiers: Breast cancer history, Implants, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging technology called TMEM-MRI (Tumor Microenvironment of Metastasis Magnetic Resonance Imaging) to help manage breast cancer. The researchers aim to determine if this method provides better insights into breast tumors, especially after certain treatments. The trial involves two groups: patients with a biopsy showing invasive ductal carcinoma and those who have completed therapy but still have a noticeable lump. Suitable candidates have been diagnosed with breast cancer, have a mass larger than 1 cm, and can undergo an MRI with contrast. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance breast cancer management.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have started any preoperative therapy for breast cancer before the TMEM-MRI is conducted.

What prior data suggests that TMEM-MRI is safe for breast cancer management?

Research shows that TMEM-MRI, a new imaging method for breast cancer, is generally safe. As a type of MRI, it does not use radiation, reducing the risk of radiation-related side effects. MRI (Magnetic Resonance Imaging) is non-invasive, meaning it does not involve surgery or entering the body, which generally makes it safer for patients.

Studies have not reported specific negative effects from TMEM-MRI, suggesting it is well-tolerated, similar to regular MRI procedures. It is important to note that this information pertains to the imaging process itself and not to any findings related to cancer risk or spread. Patients should consult their healthcare provider to understand the full details and implications of joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about TMEM-MRI imaging for breast cancer because it offers a new way to analyze the tumor microenvironment, potentially providing more detailed insights than traditional imaging methods. Unlike standard imaging techniques, TMEM-MRI focuses on TMEM doorway density, which is linked to the tumor's ability to spread. This approach could lead to more personalized treatment plans by better predicting how aggressive a cancer might be and how it might respond to therapies. By evaluating factors like MenaCalc and MenaINV, TMEM-MRI can offer a deeper understanding of tumor biology, promising more targeted and effective interventions for patients.

What evidence suggests that TMEM-MRI is effective for breast cancer management?

Research has shown that TMEM-MRI, which participants in this trial will undergo, is a promising tool for evaluating breast cancer. Studies have found a high number of TMEM doorways (specific structures in tumors) links to a greater risk of cancer spreading. TMEM-MRI aligns well with these TMEM doorway counts, which is important for predicting cancer behavior. Additionally, the density of TMEM doorways strongly predicts breast cancer outcomes, especially after treatments like chemotherapy. This suggests that TMEM-MRI could be valuable in planning treatments and monitoring the disease. ^{1 2 4 5 6}

Who Is on the Research Team?

Jesus Anampa, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a breast mass larger than 1 cm, diagnosed as invasive breast carcinoma or highly suspicious of it. It's for those who haven't had preoperative therapy and can undergo an MRI with contrast, without any history of severe claustrophobia, metallic implants incompatible with MRI, sickle cell disease, known allergies to gadolinium, or renal impairment.

Inclusion Criteria

I have a breast mass confirmed as invasive breast cancer by biopsy.

My breast mass is highly likely to be cancer, as per my radiologist.

Exclusion Criteria

Use of any investigational agent within 30 days of starting study

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I have never had breast cancer or radiation to the same breast before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

TMEM-MRI Imaging

Participants undergo TMEM-MRI to assess tumor permeability and TMEM density

2 weeks

1 visit (in-person)

Post-Imaging Analysis

Analysis of TMEM density, MenaCalc, and MenaINV from surgical specimens

0-56 days before surgery

Follow-up

Participants are monitored for safety and effectiveness after imaging and surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• FNA
• TMEM-MRI

Trial Overview The study is testing the feasibility of TMEM-MRI technology in managing operable breast cancer. Participants will undergo a 'research breast MRI' using this new imaging technique alongside standard care to see how well it works in detecting and assessing their cancer.

How Is the Trial Designed?

Group I: Pre-biopsy patients (Cohort A) Experimental Treatment 2 Interventions

Patients 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).

Group II: Post-neoadjuvant therapy patients (Cohort C) Experimental Treatment 1 Intervention

Patients 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.

Group III: Post-biopsy patients (Cohort B) Experimental Treatment 1 Intervention

Patients 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.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

University of Southern California

Collaborator

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

Functional MRI techniques, including dynamic contrast-enhanced MRI, are valuable for noninvasively assessing the blood flow and oxygenation of breast tumors, which can help predict how well they respond to neoadjuvant chemotherapy.

Advanced MRI methods like diffusion-weighted MRI and MR spectroscopy may provide insights into tumor cellularity and metabolism, enhancing our understanding of breast carcinoma characteristics during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging and blood oxygenation level-dependent magnetic resonance imaging for the assessment of changes in tumor biology with treatment. Li, SP., Padhani, AR., Makris, A.[2015]

TMEM Activity-MRI is a new imaging technique that can detect specific vascular openings associated with tumor microenvironment of metastasis (TMEM) in breast cancer, which are linked to the risk of cancer spreading.

This imaging method not only correlates with the number of TMEM doorways in tumors but also shows changes in response to treatments, such as decreased activity with the TMEM inhibitor rebastinib and increased activity with chemotherapy like paclitaxel, indicating its potential as a tool for assessing metastatic risk and monitoring treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of MRI to estimate metastatic dissemination risk and prometastatic effects of chemotherapy. Karagiannis, GS., Bianchi, A., Sanchez, LR., et al.[2023]

The study used dynamic contrast-enhanced MRI to analyze tumor blood flow and permeability in MCF7 human breast cancer implanted in mice, revealing that areas of rapid enhancement corresponded to regions with dense, permeable microcapillaries, particularly around necrotic areas.

The findings suggest that the degree of angiogenic activity induced by stress conditions in tumors, which was heightened in response to tamoxifen treatment, could provide valuable diagnostic and prognostic information when assessed through contrast-enhanced MRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors. Furman-Haran, E., Margalit, R., Grobgeld, D., et al.[2019]

Non-invasive imaging techniques, such as PET, MRI, and optical imaging, can provide crucial insights into the tumor microenvironment, helping to assess cancer aggressiveness, metastasis, and treatment response.

Current research is focused on imaging specific features of the tumor microenvironment, like inflammation and hypoxia, which can guide the development of new treatments and improve patient monitoring in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging the Tumor Microenvironment. Abadjian, MZ., Edwards, WB., Anderson, CJ.[2018]

Tamoxifen treatment in MCF7 human breast tumors led to rapid necrosis of tumor cells, indicating its potential to inhibit blood vessel growth (angiogenesis) and promote tumor regression.

Imaging techniques revealed that after tamoxifen treatment, there was a significant increase in ATP levels, suggesting enhanced energy metabolism in the tumor's reparative fibrous tissue, which may play a role in the tumor's response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging and spectroscopy of MCF7 human breast cancer: pathophysiology and monitoring of treatment. Degani, H., Furman, E., Fields, S.[2019]

The tumor microenvironment (TME) is crucial for understanding cancer progression and treatment response, as it consists of various cells and molecules that interact with tumor cells.

Novel non-invasive imaging techniques are needed to better characterize the TME, which can improve early diagnosis, guide biopsies, monitor therapies, and help develop new treatments tailored to individual patients' tumor compositions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Molecular Imaging of the Tumour Microenvironment. Foray, C., Barca, C., Backhaus, P., et al.[2021]

The tumor microenvironment (TME) plays a crucial role in the progression and metastasis of cancers, including breast cancer, by influencing drug activity and efficacy.

Targeting specific components of the TME presents a novel therapeutic approach for treating breast cancer, highlighting the potential for new treatment strategies that go beyond traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress. Bahrami, A., Hassanian, SM., Khazaei, M., et al.[2018]

Preclinical imaging strategies have revealed three distinct types of brain metastases from breast cancer: permeable metastases, nonpermeable metastases, and solitary dormant cancer cells, each likely requiring different therapeutic approaches.

Current MRI techniques may not fully capture the extent of metastatic disease in the brain, suggesting that a better understanding of these metastases could lead to the development of more effective treatments that can cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. Murrell, DH., Foster, PJ., Chambers, AF.[2021]

The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment resistance, with factors like tissue hypoxia and acidosis influencing cancer cell survival and normal cell toxicity.

Targeting and normalizing the redox parameters within the TME could potentially reduce the selection of aggressive cancer cell phenotypes, offering a new strategy for anticancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus-faced tumor microenvironment and redox. Khramtsov, VV., Gillies, RJ.[2021]

The study identifies Tumor MicroEnvironment of Metastasis (TMEM) doorways as critical sites for cancer cell dissemination in breast cancer, with their number being a prognostic indicator for metastatic recurrence.

Two methods for assessing TMEM-mediated vascular permeability—intravital imaging and fixed tissue immunofluorescence—are proposed, suggesting that combining these techniques can enhance understanding of how cancer cells spread and aid in developing treatments to prevent metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing Tumor Microenvironment of Metastasis Doorway-Mediated Vascular Permeability Associated with Cancer Cell Dissemination using Intravital Imaging and Fixed Tissue Analysis. Karagiannis, GS., Pastoriza, JM., Borriello, L., et al.[2023]

Advanced MRI techniques can provide crucial functional and structural information about tumors, such as oxygen levels, cellular growth, and blood flow, which are essential for understanding the tumor microenvironment.

Integrating these diverse MRI methods can significantly enhance tumor detection, characterization, and treatment monitoring in cancer patients, leading to better risk assessment and drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of magnetic resonance imaging in oncology. González Hernando, C., Esteban, L., Cañas, T., et al.[2021]

Citations

1. nature.com nature.com/articles/s41523-022-00463-5

Assessment of MRI to estimate metastatic dissemination ... High TMEM doorway number is associated with an increased risk of distant metastasis in human breast cancer and mouse models of breast carcinoma.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36056005/

Assessment of MRI to estimate metastatic dissemination risk ... We demonstrate that TMEM Activity-MRI correlates with primary tumor TMEM doorway counts in both breast cancer patients and mouse models, ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-00073

Magnetic Resonance Imaging for Imaging of Tumor ... This clinical trial evaluates the use of TMEM-MRI for imaging breast tumors in patients with breast cancer that can be treated by surgery (operable).

4. researchgate.net researchgate.net/publication/377313783_Signaling_events_at_TMEM_doorways_provide_potential_targets_for_inhibiting_breast_cancer_dissemination

Signaling events at TMEM doorways provide potential ... Our data suggest that cancer cell dissemination via TMEM doorways is a common mechanism of breast cancer cell dissemination to distant sites and ...

5. clinicaltrial.be clinicaltrial.be/nl/details/66957?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of... These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development ...

6. mdpi.com mdpi.com/2077-0383/10/11/2340

Breast Cancer Cell Re-Dissemination from Lung ... As such, TMEM doorways may be a common mechanism of cancer cell dissemination, present at all tumor sites and during all stages of breast cancer ...