CNS Monitoring for Breast Cancer

Overseen By Chau Dang, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: CNS metastases, Positive cytology, others

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

Compensation: Varies

Number of Visits: 4

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The researchers doing this study think that performing scans of the brain and testing cerebrospinal fluid (CSF) in people with HER2-positive breast cancer may be an effective way of identifying the early onset of CNS metastases (such as brain cancer). If the researchers can identify the early onset of CNS metastases, they can immediately treat that cancer and possibly prevent it from worsening. Currently, people with breast cancer don't usually have scans of the brain or CSF testing unless they are experiencing symptoms of CNS metastases.

Will I have to stop taking my current medications?

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 Lumbar puncture, Spinal tap, LP, MRI, Magnetic Resonance Imaging for CNS Monitoring in Breast Cancer?

MRI is highly effective in detecting brain and spinal issues in breast cancer patients, with a sensitivity of over 95% for certain brain lesions and superior accuracy in identifying spinal metastases compared to other methods. This suggests that MRI is a valuable tool in monitoring and assessing treatment response in breast cancer patients with central nervous system involvement. ^{1 2 3 4 5}

Is CNS monitoring for breast cancer safe for humans?

MRI (Magnetic Resonance Imaging) is generally considered safe for humans and is commonly used to monitor various conditions, including spinal metastases in breast cancer patients. It does not involve radiation and is non-invasive, making it a widely accepted tool for medical imaging. ^{2 6 7 8 9}

How does the CNS Monitoring treatment for breast cancer differ from other treatments?

The CNS Monitoring treatment for breast cancer is unique because it focuses on using advanced MRI techniques to detect and monitor brain metastases, which are cancer cells that have spread to the brain. This approach allows for precise assessment and follow-up, potentially improving the management of brain involvement in breast cancer patients. ^{1 3 10 11 12}

Research Team

Jessica A Wilcox, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for men and women over 18 with HER2-positive Stage II-III or IV metastatic breast cancer, but without CNS disease. They must have had at least one line of HER2 therapy and be able to undergo an MRI and a lumbar puncture. It's not open to those who can't have an MRI with gadolinium, already have CNS metastases, or show positive cytology from a lumbar puncture.

Inclusion Criteria

I can sign a consent form and my cancer is HER2 positive according to specific guidelines.

My cancer is HER2 positive according to specific guidelines.

I have stage IV HER2+ breast cancer and have received HER2 therapy but don't have brain involvement.

Exclusion Criteria

My spinal fluid test shows abnormal cells.

You cannot have an MRI scan with a contrast agent called gadolinium.

You have cancer that has spread to your brain as shown on a screening MRI.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 months

1 visit (in-person)

Initial Evaluation

Participants undergo MRI Brain and lumbar puncture to evaluate for CNS disease

1 day

1 visit (in-person)

Monitoring

Participants undergo MRI Brain and lumbar puncture at 6-month intervals to monitor for CNS metastases

12 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the monitoring phase

6 months

Treatment Details

Interventions

• Lumbar puncture
• MRI

Trial Overview The study is testing if brain scans (MRI) and cerebrospinal fluid tests (lumbar puncture) can detect early spread of breast cancer to the central nervous system in patients with HER2-positive breast cancer before symptoms appear.

Participant Groups

Group I: Stage IV HER2+ breast cancer Experimental Treatment 2 Interventions

Once enrolled on study, patients will undergo screening MRI Brain (unless already done as standard of care within 2 months on enrollment to evaluate for CNS disease) as well as lumbar puncture to evaluate for CNS disease. Once on study, patients will undergo LP and MRI Brain at 2 timepoints 6 months apart (+/- 8 weeks). LP will be performed to analyze cerebrospinal fluid for: cytology, circulating tumor cells and cell-free DNA. 6-month intervals for investigations have been based on feedback from patient advocates as well as clinical determination.

Group II: Stage II-III HER2+ breast cancer Experimental Treatment 2 Interventions

Once enrolled on study, patients will undergo screening MRI Brain (unless already done as standard of care within 2 months on enrollment to evaluate for CNS disease) as well as lumbar puncture to evaluate for CNS disease. Once on study, patients will undergo LP and MRI Brain at 2 timepoints 6 months apart (+/- 8 weeks). LP will be performed to analyze cerebrospinal fluid for: cytology, circulating tumor cells and cell-free DNA. 6-month intervals for investigations have been based on feedback from patient advocates as well as clinical determination.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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]

In a study of 32 patients with spinal metastases from breast cancer, radiotherapy (RT) resulted in excellent local tumor control, with a decrease in intraspinal tumor volume observed in all patients after treatment.

Despite some patients developing new vertebral fractures, 38% and 44% reported pain relief at 2 and 6 months post-RT, respectively, indicating that pain response was not linked to MRI findings or the presence of fractures, suggesting that MRI cannot effectively predict which patients may not respond to RT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for spinal metastases from breast cancer with emphasis on local disease control and pain response using repeated MRI. Switlyk, MD., Bruland, ØS., Skjeldal, S., et al.[2020]

In a study of 26 breast cancer patients with brachial plexopathy, MR imaging effectively identified metastases in the brachial plexus in 2 patients, highlighting its role in detecting serious complications.

The imaging also revealed other regional abnormalities in 9 patients, indicating that MR imaging can help differentiate between metastatic disease and other causes of plexopathy symptoms, guiding appropriate treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR imaging of brachial plexopathy in breast cancer patients without palpable recurrence. Lingawi, SS., Bilbey, JH., Munk, PL., et al.[2019]

MRI is superior to traditional methods like myelography and CT scans in detecting spinal metastases, particularly in identifying bone and epidural tumor involvement, based on a review of 64 studies involving 58 patients.

Due to its noninvasive nature and better visualization of soft tissue, MRI is recommended as the first-line diagnostic tool for patients suspected of having metastatic spinal disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of magnetic resonance imaging in the evaluation of metastatic spinal disease. Godersky, JC., Smoker, WR., Knutzon, R.[2022]

In a study of 142 breast cancer patients with leptomeningeal metastases, the use of the 2019 revised RANO LM criteria to assess treatment response showed a significant correlation with overall survival, indicating its effectiveness as a prognostic tool.

Patients who achieved a complete response had a median overall survival of 31.1 months, while those with progressive disease had a median survival of only 9.5 months, highlighting the importance of radiological response in predicting patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiological response of leptomeningeal metastases according to revised RANO criteria is associated with overall survival in breast cancer patients. Griguolo, G., Aldegheri, V., Bottosso, M., et al.[2023]

The use of phased-array surface coil intensity correction in MRI significantly improves the detection and assessment of spinal metastases, as shown in a study involving 50 patients and 80 spinal metastases.

MRI with this correction technique resulted in higher image quality scores and shorter reading times compared to conventional MRI, indicating enhanced diagnostic efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surface Coil Intensity Correction in Magnetic Resonance Imaging in Spinal Metastases. Ren, H., Lin, W., Ding, X.[2020]

A systematic review of MRI surveillance in children with high-grade CNS tumors found no conclusive evidence supporting its effectiveness, as no comparative studies were identified and only three retrospective studies with high bias were reviewed, involving 306 patients.

The studies indicated that recurrence rates and overall survival were similar for asymptomatic and symptomatic patients, highlighting the need for more research to determine the true benefits and risks of MRI surveillance in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The utility of routine surveillance screening with magnetic resonance imaging to detect tumor recurrence/progression in children with high-grade central nervous system tumors: a systematic review. Stevens, SP., Main, C., Bailey, S., et al.[2021]

In a study of 134 breast cancer patients, those with one or two spinal lesions on bone scans were found to have a high likelihood (70%) of benign conditions, such as facet arthrosis and compression fractures, as determined by MR imaging.

In contrast, patients with multiple spinal lesions (more than two) on bone scans were predominantly found to have malignant bone metastases (96%), indicating that the number of lesions can help differentiate between benign and malignant spinal pathologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging diagnoses of bone scan abnormalities in breast cancer patients. Kim, DS., Hong, SH., Choi, JY., et al.[2022]

In a study of 55 pediatric patients with primary brain tumors, spinal MRI using both 2D and 3D sequences showed a low false-negative rate of 4% for MRI and 16% for cerebrospinal fluid, indicating reliable diagnostic capability for detecting drop metastases.

The use of 3D T1-weighted contrast-enhanced VIBE sequences improved detection of drop metastases in 42% of patients, while 3D T2-weighted SPACE sequences made metastases more visible in 25% of patients, suggesting that these advanced imaging techniques enhance diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiological diagnosis of drop metastases from paediatric brain tumours using combination of 2D and 3D MRI sequences. Kralik, SF., O'Neill, DP., Kamer, AP., et al.[2017]

Breast MRI is a promising technology for managing women with known or suspected breast cancer, particularly in assessing the extent of disease and monitoring treatment response.

It has shown effectiveness in identifying multifocal disease and tumor recurrence, but further research is needed to explore its role in screening high-risk women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast cancer imaging with MRI. Morris, EA.[2019]

A systematic review of 24 studies involving 1580 breast cancer patients with brain metastases (BMs) highlighted that MRI is crucial for detecting and characterizing BMs, with findings varying based on the MRI technique used, the subtype of breast cancer, and the characteristics of the lesions.

Certain MRI findings were linked to prognosis and cognitive impairment in patients, indicating that MRI not only aids in diagnosis but also has potential implications for treatment strategies and understanding the biology of breast cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases from breast cancer using magnetic resonance imaging: A systematic review. Mohammadi, M., Mohammadi, S., Hadizadeh, H., et al.[2023]

Contrast-enhanced magnetic resonance (MR) imaging has shown nearly 100% sensitivity in detecting invasive breast cancer, making it a highly effective tool for diagnosis and staging.

Despite its effectiveness, there are significant challenges in standardizing techniques, interpretation criteria, and clinical indications for MR imaging, which have hindered its widespread adoption in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Orel, SG., Schnall, MD.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Brain metastasis of breast cancer; imaging evaluation]. [2012]

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

Radiotherapy for spinal metastases from breast cancer with emphasis on local disease control and pain response using repeated MRI. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

MR imaging of brachial plexopathy in breast cancer patients without palpable recurrence. [2019]

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

Use of magnetic resonance imaging in the evaluation of metastatic spinal disease. [2022]

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

Radiological response of leptomeningeal metastases according to revised RANO criteria is associated with overall survival in breast cancer patients. [2023]

6. Poland pubmed.ncbi.nlm.nih.gov

Surface Coil Intensity Correction in Magnetic Resonance Imaging in Spinal Metastases. [2020]

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

The utility of routine surveillance screening with magnetic resonance imaging to detect tumor recurrence/progression in children with high-grade central nervous system tumors: a systematic review. [2021]

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

Magnetic resonance imaging diagnoses of bone scan abnormalities in breast cancer patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Radiological diagnosis of drop metastases from paediatric brain tumours using combination of 2D and 3D MRI sequences. [2017]

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

Breast cancer imaging with MRI. [2019]

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

Brain metastases from breast cancer using magnetic resonance imaging: A systematic review. [2023]

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

MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. [2022]