MRI Screening for Brain Metastases in Breast Cancer

Overseen By Katarzyna Jerzak, MD, M.Sc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Low creatinine clearance, Pregnancy, CNS symptoms

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 2

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how often individuals with certain types of breast cancer—Triple Negative or HER2 positive at stage II or III—experience brain issues without symptoms. Participants will undergo a brain scan (such as an MRI or CT scan) and a blood test to check for cancer DNA (circulating tumor DNA testing) and provide feedback on the process. Eligible participants include those diagnosed within the last year, with no current brain symptoms, and who are open to trying this early detection method.

As an unphased trial, this study allows participants to contribute to early detection research, potentially benefiting future patients.

Will I have to stop taking my current medications?

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

What prior data suggests that this screening method is safe for patients with breast cancer?

Research has shown that MRI, or magnetic resonance imaging, is a trusted method for determining if breast cancer has spread to the brain. Often called the "gold standard," it is highly reliable and commonly used. No specific safety concerns exist for using MRI in this context.

For checking circulating tumor DNA (ctDNA), studies have found it safe and useful for monitoring cancer. This test requires a simple blood draw, which most people handle well. It helps doctors detect small pieces of cancer DNA in the blood, allowing them to track the cancer without harming patients.

In summary, both MRI and ctDNA tests are considered safe and have been used in various ways to help manage cancer effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to detect brain metastases in breast cancer patients using a combination of MRI screening, circulating tumor DNA analysis, and the Testing Morbidity Index. Unlike traditional imaging methods, this approach aims to catch metastases earlier by detecting tumor DNA in the bloodstream, potentially leading to quicker interventions. Additionally, by assessing the Testing Morbidity Index, researchers hope to better understand the impact of screening on patients' quality of life. This innovative combination could lead to more personalized and timely care for breast cancer patients at risk of brain metastases.

What evidence suggests that this screening method is effective for detecting asymptomatic brain metastases in breast cancer?

Research has shown that brain scans like MRIs, which participants in this trial will undergo, can detect cancer spread to the brain in breast cancer patients before symptoms appear. Many patients support this type of screening, with studies indicating that over 85% are willing to participate. In this trial, participants will also have their circulating tumor DNA (ctDNA) analyzed. Analyzing ctDNA is crucial because it can indicate how breast cancer might progress. Higher levels of ctDNA often suggest a poorer chance of survival, making it a valuable tool for understanding cancer's development. Both brain scans and ctDNA analysis in this trial aim to catch problems early and guide treatment decisions. ^{6 7 8 9 10}

Who Is on the Research Team?

Katarzyna Jerzak

Principal Investigator

Sunnybrook Health Science Centre

Are You a Good Fit for This Trial?

This trial is for people with stage II or III Triple Negative or HER2 positive breast cancer who haven't shown symptoms of brain metastasis. Participants must be within one year of their initial diagnosis and can join before or after systemic therapy.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My breast cancer is either Triple Negative or HER2 positive.

I have another cancer, but it won't affect this treatment's safety or results.

Exclusion Criteria

My kidney function is low, with a creatinine clearance under 30 mL/min.

I have symptoms that may suggest my cancer has spread to my brain.

Pregnant women are not permitted to participate given that the safety of IV contrast is unknown in this population

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Imaging and Biomarker Analysis

Participants undergo brain imaging and collect a blood sample for ctDNA analysis, followed by filling the Testing Morbidities Index (TMI)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for the development of brain metastasis and undergo annual chart reviews

36 months

Annual chart reviews

What Are the Treatments Tested in This Trial?

Interventions

• Analysis of circulating tumor DNA
• Brain imaging
• Testing Morbidities Index

Trial Overview The study aims to find out how common asymptomatic brain metastases are in certain breast cancer patients by using MRI (or CT scans if MRI isn't possible), analyzing blood samples for tumor DNA, and assessing feelings about the screening process.

How Is the Trial Designed?

Group I: Screening MRI Experimental Treatment 3 Interventions

One-time brain magnetic resonance (or computed tomography when magnetic resonance is contraindicated), plus circulating tumor DNA analysis, plus Testing Morbidity Index (TMI)

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Trillium Health Partners

Collaborator

Trials

8

Recruited

3,100+

MOUNT SINAI HOSPITAL

Collaborator

Trials

44

Recruited

17,000+

Princess Margaret Hospital, Canada

Collaborator

Trials

121

Recruited

40,000+

Published Research Related to This Trial

In a study of 218 patients with solitary brain tumors, preoperative whole body CT demonstrated high sensitivity (92%) and specificity (95%) for detecting metastatic disease, effectively distinguishing between primary brain tumors and metastases.

The whole body CT screening had an 88% positive predictive value for identifying systemic malignancies and a 97% negative predictive value, suggesting it is a reliable tool that could significantly influence treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Utility of Whole Body Imaging in the Evaluation of Solitary Brain Tumors. White, MD., Agarwal, N., Tonetti, DA.[2020]

MRI is the preferred method for detecting cerebral metastases due to its superior sensitivity compared to CT scans.

In cases where MRI is not available, a double-dose delayed CT can be used effectively; however, if a single lesion is found on CT, an MRI is crucial to identify any additional lesions that may not be visible on the CT scan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How can metastatic extension be assessed in the brain?]. Baleriaux, D., Lemort, M.[2006]

Circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) shows improved sensitivity for detecting gliomas compared to plasma, with an area under the curve (AUC) of 0.947 for CSF versus 0.741 for plasma, indicating it may be a more effective biomarker for tumor genetics.

Higher-grade gliomas demonstrate greater sensitivity for ctDNA detection, suggesting that targeted genetic analysis of CSF could enhance diagnostic performance, especially in more aggressive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance. McMahon, JT., Studer, M., Ulrich, B., et al.[2022]

In a patient with HER2-positive metastatic breast cancer and brain metastases, liquid biopsy of cerebrospinal fluid (CSF) revealed significant genomic alterations, including TP53 and PIK3CA mutations, which can help track tumor evolution during treatment.

Post-treatment analysis showed that while ctDNA levels decreased in plasma, indicating control of disease outside the CNS, levels increased in the CSF, suggesting limited treatment effectiveness for brain metastases, highlighting the need for better management strategies for CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases. Siravegna, G., Geuna, E., Mussolin, B., et al.[2021]

CSF circulating tumor DNA (ctDNA) detection showed a 100% sensitivity in identifying cancer-associated gene mutations in patients with meningeal carcinomatosis (MC), outperforming traditional CSF cytology (71% sensitivity) and neuroimaging (63% sensitivity).

The study involved 35 patients, primarily with lung cancer, and highlights the potential of using CSF ctDNA as a more reliable diagnostic tool for MC, especially in cases where CSF cytology and neuroimaging yield negative results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the cerebrospinal fluid ctDNA detection by next-generation sequencing in the diagnosis of meningeal Carcinomatosis. Zhao, Y., He, JY., Zou, YL., et al.[2020]

Circulating tumor DNA (ctDNA) mutations, particularly in genes like TP53, PIK3CA, and ESR1, are significantly associated with cancer recurrence and poor survival outcomes in breast cancer patients, based on a meta-analysis of 69 studies involving 5736 patients.

High levels of cell-free DNA (cfDNA) are linked to breast cancer presence and can predict axillary lymph node metastasis, although their detection rates are not sufficient for effective breast cancer screening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer: A meta-analysis. Lee, JH., Jeong, H., Choi, JW., et al.[2022]

The Idylla ctDNA assay demonstrated high accuracy in detecting metastatic melanoma, with 91% sensitivity and 96% specificity, making it a reliable tool for monitoring disease progression alongside traditional imaging methods.

Changes in plasma ctDNA levels provided earlier indications of disease progression, detecting changes an average of 82 days before conventional CT imaging, suggesting that ctDNA could be a valuable complement for assessing treatment response in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Relationship between Idylla Plasma ctBRAF V600 Mutation Detection and Tumor Burden in Patients with Metastatic Melanoma. Linder, MW., Egger, ME., Van Meter, T., et al.[2022]

In a study involving 60 patients suspected of having brain metastases, both contrast-enhanced CT scans and plain MRI were evaluated for their ability to detect these metastases.

The results indicated that neither CT nor MRI was clearly superior in sensitivity for detecting brain metastases, suggesting that both imaging methods are equally effective in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of brain metastases. Comparison of computerized tomography (CT) and magnetic resonance imaging (MRI). Taphoorn, MJ., Heimans, JJ., Kaiser, MC., et al.[2019]

In a study of 38 patients undergoing stereotactic radiosurgery (SRS) for brain metastases, delayed MRI scans (10-15 minutes post-contrast injection) detected significantly more brain metastases, with 35.3% of subjects showing at least one new lesion in the second scan compared to the first.

The volume of detected brain metastases also increased significantly with time delay, with a 25.4% increase in tumor volume between the first and second scans, suggesting that delayed imaging can improve treatment planning and reduce the risk of missing treatable tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes. Kushnirsky, M., Nguyen, V., Katz, JS., et al.[2016]

MRI is the most sensitive imaging technique for detecting hidden lesions in metastatic breast cancer, identifying about 15% of cases that may not be visible through other methods.

Advanced MRI techniques, such as diffusion and perfusion imaging, provide over 95% specificity for diagnosis and are essential for monitoring treatment response, especially when considering neurosurgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brain metastasis of breast cancer; imaging evaluation]. Gerber, S., Ollivier, L., Ala-Eddine, C., et al.[2012]

Circulating tumor DNA (ctDNA) can be used as a biomarker in breast cancer to identify specific genetic alterations that guide targeted treatments, particularly in metastatic cases, with approved assays for mutations like PIK3CA and ESR1.

In early-stage breast cancer, ctDNA analysis may detect disease relapse up to 10 months before traditional imaging methods, potentially allowing for timely treatment adjustments, although this needs further validation through prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor DNA in breast cancer: a biomarker for patient selection. Agostinetto, E., Nader-Marta, G., Ignatiadis, M.[2023]

The study involved 31 breast cancer patients and utilized circulating tumor DNA (ctDNA) analysis at three key time points to assess tumor progression and treatment effectiveness, revealing a total of 500 somatic mutations across samples.

Mutations in specific genes like KMT2C in ctDNA were identified as potential indicators of breast cancer recurrence, suggesting that ctDNA could be a valuable tool for monitoring patients over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Circulating Tumor DNA to Predict Neoadjuvant Therapy Effectiveness and Breast Cancer Recurrence. Hao, S., Tian, W., Zhao, J., et al.[2023]

Cerebrospinal fluid (csf) ctDNA detection is more sensitive than traditional cytology for diagnosing meningeal metastasis in non-small cell lung cancer (NSCLC), as shown in a study of 21 patients.

The ctDNA in cerebrospinal fluid not only provides a higher detection rate and mutation abundance compared to peripheral blood but also allows for dynamic monitoring of disease progression and treatment response, potentially identifying drug resistance earlier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Value of Cerebrospinal Fluid ctDNA in Patients with Non-small Cell Lung Cancer Meningeal Metastasis]. Zhang, K., Dai, Z., Liu, S., et al.[2021]

Citations

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