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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to detect early signs of brain cancer in individuals with HER2-positive breast cancer through brain scans and spinal fluid tests. The goal is to identify cancer spread to the brain more quickly, enabling immediate treatment and potentially preventing the cancer from worsening. Individuals with Stage II-IV HER2-positive breast cancer who have not experienced brain-related symptoms may be suitable candidates. Participants will undergo a lumbar puncture (a procedure to collect spinal fluid) and MRI scans every six months. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to earlier detection and treatment strategies.

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 prior data suggests that these monitoring techniques are safe for patients with breast cancer?

Research has shown that both lumbar punctures and MRIs are generally well-tolerated. A lumbar puncture involves taking a small amount of fluid from the spine to help diagnose and monitor health conditions. It might cause some discomfort or a headache, but serious issues are rare.

Studies have found that MRI scans are safe and effective for spotting changes in the brain. An MRI uses magnets and radio waves to create detailed pictures, and there are no known long-term side effects. Any risks are usually related to comfort, such as feeling claustrophobic or hearing loud noises during the scan.

Overall, these procedures are widely used in medicine and are considered safe for detecting changes related to cancer spread in the brain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it offers a new approach to monitoring central nervous system (CNS) involvement in HER2+ breast cancer patients. Unlike standard care options that primarily focus on treating existing brain metastases, this trial utilizes lumbar punctures and MRI scans to detect CNS disease early by analyzing cerebrospinal fluid for tumor cells and DNA. This method could potentially catch issues sooner, providing a proactive way to manage and treat the cancer before it progresses further. By monitoring at set intervals, researchers aim to gain a clearer understanding of CNS disease development, ultimately improving patient outcomes.

What evidence suggests that this protocol is effective for identifying early CNS metastases in HER2-positive breast cancer?

This trial will use MRI scans and lumbar punctures to monitor brain metastases in patients with HER2-positive breast cancer. Research has shown that cancer spreads to the brain in 20-40% of these patients. Early detection can lead to better treatment outcomes. MRI scans can identify brain metastases early, potentially improving survival rates. Studies have found that analyzing the fluid around the brain and spine through a lumbar puncture can detect cancer cells and DNA, providing a detailed view of cancer spread. Using these methods together can identify metastases before symptoms appear, allowing for quicker treatment and possibly preventing cancer progression. Participants in this trial will undergo these procedures at two timepoints, six months apart, to evaluate for CNS disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Jessica A Wilcox, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05130840

Monitoring for Cancer Spread to the Central Nervous ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12563209/

Molecular Analysis of Cerebrospinal Fluid Tumor-Derived ... Metastasis to the brain occurs in an estimated 20–40% of breast cancer patients with a median overall survival of 1 month when untreated and 1–2 ...

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1210873/full

Long-term response to sequential anti-HER2 therapies ... The prospective, observational registHER study confirmed a prolonged OS of 17.5 months in patients with newly diagnosed HER2+ CNS metastases ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34518

Neurologic complications of breast cancer - Atkins - 2023 The authors present a review of the neurologic complications of breast cancer arising from disease dissemination or secondary to treatment.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11140729/

implications for treating the LM tumor with anti-HER2 therapy We show that HER2 is amplified on CSF tumor cells in 62% (16/26) of LMD breast cancer patients. 10/26 (38%) patients had discordant HER2- ...

6. ejbc.kr ejbc.kr/DOIx.php?id=10.4048/jbc.2023.26.e40

Intrathecal Catheter for Chemotherapy in Leptomeningeal ... Infusing chemotherapy using an implanted catheter is an efficient option for managing IT chemotherapy with a good tolerance profile.