PEM vs Liquid Biopsy for Breast Cancer

Overseen By Samira Taeb, MSc

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Pregnancy, Breast-feeding, Allergies to F-18 FDG, others

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

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Liquid Biopsy for breast cancer?

Research shows that liquid biopsy, which involves analyzing circulating tumor cells (CTCs) in the blood, can help monitor breast cancer progression and treatment response. It is a non-invasive method that can detect cancer cells earlier and in smaller numbers compared to traditional tissue biopsies, making it a valuable tool for ongoing cancer management. ^{1 2 3 4 5}

Is liquid biopsy safe for breast cancer patients?

In a study involving 127 patients with metastatic breast cancer, the use of a liquid biopsy method called Cellcollector showed a high incidence of adverse events (66.9%) and severe adverse events (39.8%). ^{2 6 7 8 9}

How is the treatment 'Liquid Biopsy and PEM' different from other breast cancer treatments?

Liquid biopsy is a unique and non-invasive method that detects cancer cells in the blood, allowing for real-time monitoring of breast cancer without the need for painful tissue biopsies. It can identify circulating tumor cells and DNA, providing a comprehensive view of the disease's progression and potentially detecting cancer earlier than traditional methods. ^{1 2 3 4 10}

What is the purpose of this trial?

The goal of this research study is to evaluate the performance of two experimental tests, namely Liquid Biopsy and Positron Emission Mammography (PEM) in women at high risk of breast cancer. The plan for this study is to assess whether findings from the combination or each individual test can assist radiologists in visualizing and characterizing beast abnormalities. Liquid Biopsy is a blood test that can detect early tumours in patients with malignancies, while PEM is an imaging tool equipped with a high-resolution camera that uses a low dose of injected positron emitting isotope to locate breast tumours. Participation in this study entails a blood draw for Liquid Biopsy test and a PEM imaging exam before undergoing a magnetic resonance imaging (MRI) - guided biopsy for a suspicious breast lesion. If PEM and/or Liquid Biopsy provide accurate information to assist radiologists in visualizing and characterizing breast abnormalities, this method may serve as the first step towards establishing these genomic and new imaging technologies as new diagnostic modalities and ultimately reduce the unnecessary biopsies and anxiety in high-risk populations.

Research Team

Vivianne Freitas, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for women at high risk of breast cancer who are due to have an MRI-guided biopsy for a suspicious breast lesion. Participants will undergo two experimental tests: a blood test called Liquid Biopsy and an imaging exam known as Positron Emission Mammography (PEM).

Inclusion Criteria

I am older than 18 years.

I can understand and am willing to sign the consent form.

I am scheduled for an MRI-guided biopsy due to high-risk lesions found during screening.

Exclusion Criteria

High-risk individuals with screening-imaging studies without suspicious lesions detected by the standard of care mammogram and/or MRI

Individuals who are pregnant or who think they may be pregnant

Individuals who are breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a blood draw for Liquid Biopsy and a PEM imaging exam before an MRI-guided biopsy

1 day

1 visit (in-person)

Follow-up

Follow-up blood and tissue samples may be requested post-surgery if malignancy is confirmed

Varies

Outcome Evaluation

Evaluation of the performance of PEM and Liquid Biopsy in visualizing and characterizing breast abnormalities

3 years

Treatment Details

Interventions

• Liquid Biopsy
• Positron Emission Mammography (PEM)

Trial Overview The study aims to see if results from the Liquid Biopsy, which detects early tumors through blood analysis, match up with images from PEM. PEM uses a special camera and injected isotopes to find tumors in the breast.

Participant Groups

Group I: Liquid Biopsy and Positron Emission Mammography (PEM) Experimental Treatment 2 Interventions

To perform the Liquid Biopsy assays, a baseline blood sample will be collected prior to the MRI-guided biopsy, and a follow-up blood and a tissue sample (if available) may be requested post-surgery If malignancy is confirmed by the standard of care histopathology results. To perform the Positron Emission Mammography (PEM), participants will be injected with 74 megabecquerel (MBq) of commercially distributed 2-\[fluorine-18\]-fluoro-2-deoxy-D-glucose (F-18 FDG). Following a delay of one hour for F-18 FDG uptake, the study participants will undergo a bilateral 4-view combination PEM scan.

Liquid Biopsy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Liquid Biopsy for:

• Monitoring and diagnosis of various cancers including breast cancer

Approved in European Union as Liquid Biopsy for:

• Non-invasive diagnosis and monitoring of cancer, including breast cancer

Approved in Canada as Liquid Biopsy for:

• Diagnosis and monitoring of cancer, including breast cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Radialis Inc.

Industry Sponsor

Trials

1

Recruited

100+

The Princess Margaret Cancer Foundation

Collaborator

Trials

7

Recruited

1,300+

Findings from Research

A study involving 92 breast cancer patients demonstrated that RT-qPCR can effectively detect specific gene expressions in circulating tumor cells (CTCs) at the single-cell level, highlighting its sensitivity and specificity for molecular characterization.

The results showed significant heterogeneity in gene expression among patients, with CTCs from operable and metastatic breast cancer patients expressing various genes, suggesting that RT-qPCR may provide more positive results than the CellSearch system for detecting CTCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR. Strati, A., Markou, A., Parisi, C., et al.[2022]

Liquid biopsy offers a less invasive alternative to traditional tissue biopsy for monitoring breast cancer, utilizing circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) found in the bloodstream.

This method allows for real-time tracking of tumor evolution and could improve disease management for postmenopausal women with breast cancer, addressing the limitations of invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A headlight on liquid biopsies: a challenging tool for breast cancer management. Massihnia, D., Perez, A., Bazan, V., et al.[2017]

The study demonstrated that circulating tumor cells (CTCs) can be effectively captured from various breast cancer subtypes using EpCAM-based immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE/FACS), although claudin-low subtypes showed significantly lower capture rates.

The method allows for the isolation of high-quality RNA from CTCs, which is suitable for RNA sequencing, enabling detailed gene expression analysis that can help in understanding the molecular characteristics of different breast cancer subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EpCAM based capture detects and recovers circulating tumor cells from all subtypes of breast cancer except claudin-low. Ring, A., Mineyev, N., Zhu, W., et al.[2018]

Circulating Tumor Cells (CTCs) are crucial for understanding breast cancer metastasis, as they can migrate to vital organs like the lungs and brain even in early stages, highlighting the aggressive nature of this cancer.

Liquid biopsy, which isolates CTCs from blood samples, offers a non-invasive and potentially earlier detection method for breast cancer compared to traditional tissue biopsies, making it a promising tool for improving diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection Methods and Clinical Applications of Circulating Tumor Cells in Breast Cancer. Zhang, H., Lin, X., Huang, Y., et al.[2021]

Circulating tumor cells (CTCs) in blood can be effectively monitored through a simple blood withdrawal procedure, providing a non-invasive method for tracking cancer progression and treatment response in patients with various cancers, including breast, colorectal, prostate, and lung cancer.

The study highlights the clinical utility of CTC testing in different treatment phases (neoadjuvant, adjuvant, and palliative), supporting its role in predicting treatment efficacy and enhancing monitoring of malignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor cells: what we know, what do we want to know about them and are they ready to be used in clinics? Bielčiková, Z., Jakabová, A., Pinkas, M., et al.[2022]

In a study of 254 metastatic breast cancer patients, the EPISPOT assay detected viable circulating tumor cells (CTC) in 59% of cases, indicating a significant presence of these cells in the bloodstream.

The presence of viable CTC, as measured by both the EPISPOT and CellSearch assays, was linked to overall survival, with the combination of both methods providing the strongest prediction of patient outcomes, highlighting their prognostic relevance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Ramirez, JM., Fehm, T., Orsini, M., et al.[2022]

In a study of 190 patients, the Cellcollector method successfully detected circulating tumor cells (CTCs) in 74.8% of patients with metastatic breast cancer, while all patients with benign tumors tested negative for CTCs, demonstrating high specificity (100%) and moderate sensitivity (74.8%).

The study suggests that using Cellcollector for CTC detection not only aids in diagnosing metastatic breast cancer but also allows for further molecular testing, which could enhance clinical decision-making in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Circulating tumor cells in patients with breast tumors were detected by a novel device: a multicenter, clinical trial in China]. Li, JB., Geng, CZ., Yan, M., et al.[2018]

Circulating tumor cells (CTCs) can be captured and analyzed through liquid biopsies, providing a non-invasive alternative to traditional tissue biopsies for cancer diagnostics, particularly in breast, prostate, colon, and lung cancers.

Recent advancements in culturing viable CTCs from patients with advanced cancer have opened up new possibilities for functional studies, which can help identify metastatic cell properties and potential therapeutic targets for drug screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Studies on Viable Circulating Tumor Cells. Pantel, K., Alix-Panabières, C.[2019]

Circulating tumor cells (CTCs) are emerging as important liquid-based biomarkers in oncology, particularly for breast cancer, offering a new way to monitor treatment response and patient outcomes.

The review highlights the use of the FDA-approved CellSearch platform for CTC enumeration, emphasizing its potential in assessing radiation treatment response and ongoing clinical studies exploring its predictive capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions. Goodman, CR., Speers, CW.[2021]

Liquid biopsy offers a non-invasive alternative to traditional tissue biopsy for early breast cancer detection, allowing for a more comprehensive analysis of tumor characteristics through the study of circulating tumor components like ctDNA, CTCs, and ctRNA.

This review highlights recent advancements in technologies and analytes used in liquid biopsies, emphasizing their potential to provide a complete molecular picture of breast cancer, which is crucial for effective monitoring and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and achievements of liquid biopsy technologies employed in early breast cancer. Alba-Bernal, A., Lavado-Valenzuela, R., Domínguez-Recio, ME., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Gene expression profile of circulating tumor cells in breast cancer by RT-qPCR. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A headlight on liquid biopsies: a challenging tool for breast cancer management. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

EpCAM based capture detects and recovers circulating tumor cells from all subtypes of breast cancer except claudin-low. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Detection Methods and Clinical Applications of Circulating Tumor Cells in Breast Cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Circulating tumor cells: what we know, what do we want to know about them and are they ready to be used in clinics? [2022]

6. England pubmed.ncbi.nlm.nih.gov

Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Circulating tumor cells in patients with breast tumors were detected by a novel device: a multicenter, clinical trial in China]. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Functional Studies on Viable Circulating Tumor Cells. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Challenges and achievements of liquid biopsy technologies employed in early breast cancer. [2023]