Breast Cancer
Conditions
Keywords
TMEM;, Magnetic resonance imaging (MRI)
Brief 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).
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).
Interventions
DEVICETMEM-MRI
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.
PROCEDUREFNA
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).
Sponsors
University of Southern California
Montefiore Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
No need for masking, all patients will undergo TMEM-MRI
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor permeability assessed by TMEM-MRI | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TMEM density in breast cancer patients | 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 | 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 |
| MenaCalc | 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 | 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 |
| MenaInv | 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 | 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 |
| Circulating Tumor Cells (CTCs) | Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery | 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. |
Countries
United States
Contacts
Primary ContactJesus Anampa, MD, MS
Outcome results
None listed