MRI Screening for Brain Metastases in Breast Cancer

Overseen By Ivy Ricca, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Chronic kidney disease, Pregnancy, Brain metastases, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

214 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether MRI scans (Magnetic Resonance Imaging) can detect breast cancer that has spread to the brain. It compares different groups, such as those with specific types of breast cancer (HR+, HER2+, or Triple Negative), to determine if regular MRI screenings make a difference. Participants should have breast cancer that has spread or recurred and be about to start certain treatments. The goal is to see if MRI screenings can catch brain metastases early, potentially improving care and outcomes. As an unphased trial, this study allows patients to contribute to groundbreaking research that could enhance early detection and treatment strategies.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What prior data suggests that magnetic resonance imaging is safe for screening brain metastases in breast cancer?

Research has shown that MRI (magnetic resonance imaging) is safe for people. In one study, researchers used MRI to monitor women with BRCA mutations, which increase the risk of breast cancer. The MRI scans detected most cancers early. Another study found that MRI screening reduced the risk of dying from breast cancer over 20 years.

MRI does not use radiation, making it safer than some other scans. Most people tolerate MRI well, experiencing few side effects. Some might feel uncomfortable due to the noise or being in a small space, but serious issues are rare.

Overall, MRI is a well-tested and safe method for screening, including for conditions like cancer spread to the brain in breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using MRI screening for brain metastases in breast cancer patients because it offers a non-invasive way to detect brain involvement early. Unlike standard practices that might wait for symptoms to appear before imaging, this approach could allow for earlier interventions, potentially improving outcomes. By regularly monitoring with MRIs, doctors can catch any changes much sooner than waiting for a patient's condition to change visibly. This proactive method might lead to better management of metastatic breast cancer, offering hope for extending patient survival and quality of life.

What evidence suggests that MRI screening is effective for detecting brain metastases in breast cancer?

Research has shown that MRI scans can detect cancer that has spread to the brain in breast cancer patients. One study highlighted a high risk of this occurrence in various types of breast cancer, underscoring the importance of screening. In this trial, some participants will receive initial MRI screening, while others will not. MRI provides a safe and painless method to capture detailed images of the brain, aiding in early problem detection. By identifying these issues sooner, there may be a better opportunity to manage or treat them effectively. This makes MRI a potentially valuable tool for early detection and management of cancer spread to the brain in breast cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Ayal Aizer, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed breast cancer, either starting first/second-line chemo for metastatic disease or managing inflammatory breast cancer. They must expect to live more than 12 weeks and agree to use birth control. It's not for those with MRI contraindications, severe kidney disease, gadolinium allergies, or existing brain metastases.

Inclusion Criteria

Participants must have a life expectancy of greater than 12 weeks.

Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.

I am starting treatment for breast cancer that has spread or cannot be surgically removed.

Exclusion Criteria

Pregnant women are excluded from this study because gadolinium-based agents have not been proven to be safe to administer to a developing fetus. Similarly, breastfeeding women will be excluded from this study.

I have been diagnosed with brain metastases before.

You have had a severe allergic reaction to gadolinium in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial MRI Screening

Participants undergo an initial MRI screening of the brain to evaluate for metastases

1 week

1 visit (in-person)

Follow-up MRI Screening

Participants receive additional MRI screenings every six months for two years if no initial metastases are found

24 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Magnetic Resonance Imaging

Trial Overview The study tests if MRI can effectively screen for the spread of breast cancer to the brain in patients undergoing certain treatments. The goal is to assess how useful MRI scans are in detecting these brain metastases early on.

How Is the Trial Designed?

Group I: Triple Negative Breast Cancer Experimental Treatment 1 Intervention

* An initial MRI screening will be conducted * If negative, patients will receive a second MRI of the brain at first systemic progression after study entry

Group II: Inflammatory Breast Cancer Managed with Curative Intent Experimental Treatment 1 Intervention

* Patients will receive an initial screening magnetic resonance imaging (MRI) of the brain * If no evidence of intracranial involvement is identified, additional screening MRIs of the brain every six months for two years and at initial systemic progression.

Group III: HR+ or HER2+ Metastatic Breast Cancer - Screening Arm Experimental Treatment 1 Intervention

* An initial MRI screening will be conducted * If negative, patients will receive a second MRI of the brain at first systemic progression after study entry

Group IV: HR+ or HER2+ Metastatic Breast Cancer - No Screening Arm Active Control 1 Intervention

No initial MRI screening will be conducted

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Conquer Cancer Foundation

Collaborator

Trials

22

Recruited

4,000+

Published Research Related to This Trial

In a study of 88 female patients with breast cancer who underwent surgery for brain metastases, the presence of intra-tumoral necrosis was found to be significantly associated with overall survival, with a median survival of 14.5 months for those with necrosis compared to 22.5 months for those without.

The study also revealed that certain characteristics, such as a shorter time interval between breast cancer diagnosis and brain metastases and preoperative leukocytosis, were linked to the presence of necrosis, indicating that radiographic features on MRI can reflect underlying tumor biology and patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome. Michel, A., Dinger, T., Darkwah Oppong, M., et al.[2022]

A clinically relevant mouse model was developed to study melanoma brain metastases, using longitudinal MRI to track tumor development and blood-tumor barrier permeability over time.

The study found that both enhancing and nonenhancing brain metastases coexist, with many metastases transitioning from a nonenhancing to an enhancing phenotype, highlighting the dynamic nature of these tumors and their potential responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vivo longitudinal MRI study: an assessment of melanoma brain metastases in a clinically relevant mouse model. Henry, MN., Chen, Y., McFadden, CD., et al.[2015]

Early whole-brain radiotherapy effectively reduces the outgrowth of breast cancer metastases from individual disseminated cancer cells, as shown in a study using the MDA-MB-231-BR-HER2 cell model.

Despite the reduction in metastasis outgrowth, the number of nonproliferative cancer cells in the brain remained unchanged, indicating that these dormant cells may evade treatment and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI surveillance of cancer cell fate in a brain metastasis model after early radiotherapy. Murrell, DH., Zarghami, N., Jensen, MD., et al.[2022]

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]

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]

Whole brain radiotherapy (WBRT) significantly reduced the size of brain metastases in a breast cancer mouse model, as shown by MRI, indicating its efficacy in treating these tumors.

MRI techniques revealed that WBRT increased blood-tumor-barrier (BTB) permeability and induced apoptosis in tumor cells, suggesting that combining WBRT with other treatments could enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis. Crowe, W., Wang, L., Zhang, Z., et al.[2020]

In a study of 183 patients with non-small cell lung cancer (NSCLC), early screening for brain metastases (BM) using MRI revealed a significantly higher incidence of BM (20.8%) compared to a control group (4.6%) that only received MRI if they showed neurological symptoms.

While the MRI screening did not lead to a significant difference in overall survival between the groups, it did allow for timely treatment and improved quality of life, particularly for patients with BM alone, who had a longer survival time (49 weeks) compared to those with multiple systemic metastases (27 weeks).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening of brain metastasis with limited magnetic resonance imaging (MRI): clinical implications of using limited brain MRI during initial staging for non-small cell lung cancer patients. Kim, SY., Kim, JS., Park, HS., et al.[2022]

In a study of patients undergoing GammaKnife™ MRI, 43.9% experienced growth of existing brain metastases, while 32.9% developed additional metastases, indicating a significant prevalence of disease progression.

Factors such as the initial brain metastasis velocity and the time between diagnostic MRI and GammaKnife MRI were linked to increased risks of new or enlarged brain metastases, but these changes did not significantly impact overall survival or the rate of distant intracranial failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes. Mereniuk, TR., Burney, HN., Lautenschlaeger, T., et al.[2023]

Preclinical imaging strategies have revealed three distinct types of brain metastases from breast cancer: permeable metastases, nonpermeable metastases, and solitary dormant cancer cells, each likely requiring different therapeutic approaches.

Current MRI techniques may not fully capture the extent of metastatic disease in the brain, suggesting that a better understanding of these metastases could lead to the development of more effective treatments that can cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. Murrell, DH., Foster, PJ., Chambers, AF.[2021]

In a mouse model of breast cancer brain metastasis, half brain irradiation effectively induced DNA damage in tumors, which remained unrepaired over time, while normal brain tissue showed recovery, indicating a differential response to radiation.

Higher radiation doses (16 and 24 Gy) significantly reduced tumor cell density and increased the size of surviving tumor cell nuclei, suggesting that while radiation can damage tumor cells, some may continue to progress in the cell cycle despite the damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Half brain irradiation in a murine model of breast cancer brain metastasis: magnetic resonance imaging and histological assessments of dose-response. Zarghami, N., Murrell, DH., Jensen, MD., et al.[2018]

A study involving 412 brain metastases from 106 breast cancer patients demonstrated that machine learning can effectively predict receptor status (ER, PR, HER2) using MR imaging features, achieving high accuracy with AUC values of 0.82 for ER+, 0.73 for PR+, and 0.74 for HER2+.

This approach allows for continuous monitoring of receptor expressions in metastatic lesions, which is crucial for personalizing treatment strategies in patients with brain metastases, potentially leading to better-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discordant and Converting Receptor Expressions in Brain Metastases from Breast Cancer: MRI-Based Non-Invasive Receptor Status Tracking. Heitkamp, A., Madesta, F., Amberg, S., et al.[2023]

Citations

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Brain Imaging Surveillance for Patients With Metastatic ... These data confirm a substantially high risk of brain metastases across breast cancer subtypes and support the need for a definitive RCT ...

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Diagnostics and Screening in Breast Cancer with Brain and ... This review discusses the evidence behind screening for breast cancer that has spread to the central nervous system, as well as new methods of diagnosis.

3. thebreastonline.com thebreastonline.com/article/S0960-9776(25)00575-2/fulltext

Brain imaging screening in metastatic breast cancer A total of 529 physicians from 50 countries (80 % European) responded, mostly medical oncologists (70 %) working in academic hospitals (53 %).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04030507

NCT04030507 | Screening Magnetic Resonance Imaging ... This research study is studying the usefulness of magnetic resonance imaging (MRI) to screen for brain metastases (spread of the breast cancer to the brain).

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Brain imaging screening in metastatic breast cancer Screening magnetic resonance imaging of the brain in patients with metastatic breast cancer managed with first/second line chemotherapy or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4014797/

Magnetic resonance imaging in breast cancer: A literature ... In a cohort of 496 women, Passaperuma et al[42] concluded that MRI surveillance of women with BRCA mutations detects most breast cancers at an early stage.

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MRI Surveillance and Breast Cancer Mortality in Women ... At 20 years, the risk of breast cancer mortality was 3.2% in the MRI surveillance group compared with 14.9% for women who did not undergo MRI ...

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Recommendation: Breast Cancer: Screening There is insufficient evidence to recommend for or against supplemental screening using breast ultrasonography or MRI in women who have dense ...

9. insightsimaging.springeropen.com insightsimaging.springeropen.com/articles/10.1186/s13244-024-01653-4

The paradox of MRI for breast cancer screening: high-risk and ... This trial demonstrated that breast MRI screening can lead to a shift in tumour stage upon detection, thereby reducing the incidence of late- ...

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MRI-only breast cancers are less aggressive than ... Our data provide evidence that MRI-only lesions are biologically less aggressive and of lower stage, offering the potential of earlier treatment chance.