MRI Screening for Brain Metastases in Breast Cancer

(SYMPToM Trial)

Overseen By Ellen Warner, MD FRCPC MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Severe claustrophobia, Pregnancy, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, 50 women with either HER2+ or triple negative metastatic breast cancer but no known brain metastases will be recruited at the Sunnybrook Odette Cancer Centre. They will be randomized to undergo either routine MRI screening of their brain every 4 months for 1 year or standard-of-care (MRI only if symptoms of brain metastases develop). Patients will complete questionnaires about quality of life and cancer-related anxiety throughout the study. To determine why some cancers spread to the brain and others do not, blood samples will be collected to analyze the genetic makeup of patients' breast cancers. Finally, a novel MRI imaging technique that detects abnormal metabolism in the brain will be used to help detect brain metastases even earlier than the standard MRI. If results are promising, we will conduct a large multi-centre randomized trial to determine whether screening for brain metastases can help them live longer with improved quality of life.

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 MRI screening for brain metastases in breast cancer?

MRI is a valuable tool for detecting and monitoring brain metastases from breast cancer, as it helps in diagnosis and targeted therapy. Studies show that MRI findings can be associated with prognosis and survival outcomes, making it an important part of managing breast cancer patients with brain metastases. ^{1 2 3 4 5}

Is MRI screening generally safe for humans?

MRI screening is generally considered safe for humans. However, it can sometimes lead to false-positive results, which might cause unnecessary stress and additional testing. ^{6 7 8 9 10}

How is MRI screening for brain metastases in breast cancer different from other treatments?

MRI screening is unique because it uses advanced imaging techniques to detect and monitor brain metastases in breast cancer patients, allowing for early detection and targeted therapy. Unlike other treatments, it provides detailed information about the size, shape, and characteristics of brain lesions, which can help guide treatment decisions and improve outcomes. ^{2 5 11 12 13}

Research Team

Katarzya J Jerzak, MD MSc FRCPC

Principal Investigator

University of Toronto

Eligibility Criteria

This trial is for women over 18 with HER2+ or triple negative metastatic breast cancer, diagnosed within the last 12 weeks and without symptoms or known brain metastases. It's not open to those with other cancers that could affect the study results.

Inclusion Criteria

I am 18 years old or older.

My breast cancer is either triple negative or HER2 positive.

My cancer spread to other parts was diagnosed within the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either routine MRI screening every 4 months or symptom-directed surveillance for brain metastases

12 months

Baseline, 4 months, 8 months, 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• MRI screening

Trial Overview The study compares routine MRI screening every four months against MRIs only when symptoms appear, in detecting brain metastases early. Participants will also provide blood samples and complete questionnaires on life quality and anxiety.

Participant Groups

Group I: MRI screening Experimental Treatment 1 Intervention

Contrast-enhanced MRI and Chemical Exchange Saturation Transfer (CEST) MRI of the brain at baseline, 4 months, 8 months and 12 months.

Group II: Symptom-directed surveillance Active Control 1 Intervention

Imaging of the brain will take place only if patients develop symptoms that are suggestive of brain metastases (e.g. headaches, vision changes, gait instability).

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Harvard University

Collaborator

Trials

237

Recruited

588,000+

Findings from Research

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]

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]

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]

MRI screening for high-risk women can significantly increase the detection of breast cancers, particularly identifying cancers before they spread to lymph nodes.

While MRI offers benefits in cancer detection, it also carries risks of false positives, which may result in unnecessary additional imaging or benign biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening MRI for women at high risk for breast cancer. Lehman, CD.[2019]

References

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

Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC). [2022]

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

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

3. 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]

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

Contralateral Breast Screening with Preoperative MRI: Long-Term Outcomes for Newly Diagnosed Breast Cancer. [2022]

5. Austria pubmed.ncbi.nlm.nih.gov

Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome. [2022]

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

The utility of magnetic resonance imaging in early-stage breast cancer survivors-An institutional experience and literature review. [2021]

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Baseline Screening MRI Uptake and Findings in Women with ≥ 20% Lifetime Risk of Breast Cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical surveillance compared with clinical and magnetic resonance imaging surveillance for brain metastasis: a feasibility survey. [2019]

9. Canada pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Imaging as an Adjunct to Mammography for Breast Cancer Screening in Women at Less Than High Risk for Breast Cancer: A Health Technology Assessment. [2018]

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

Screening MRI for women at high risk for breast cancer. [2019]

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

Incidence of Brain Metastasis at the Initial Diagnosis of Lung Squamous Cell Carcinoma on the Basis of Stage, Excluding Brain Metastasis. [2017]

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

Incidence of Brain Metastases in Women Treated With Neoadjuvant Chemotherapy for Breast Cancer: Implications for Screening. [2023]

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

Deep-Learning Detection of Cancer Metastases to the Brain on MRI. [2021]