A study of the feasibility of randomising women and men with HER2 Positive metastatic breast cancer to Central Nervous System surveillance versus not.

In spring 2023 Make 2nds Count awarded £219,560 over 3 years to the HER2-CNS.

SURVEILLANCE study. This vital research will investigate MRI screening for breast cancer which has spread to the brain, before patients become symptomatic. The study is taking place across the UK and Ireland and will start recruiting secondary breast cancer patients in 2024. 

The Co-Chief Investigators of this study are Prof Carlo Palmieri, Professor of Translational Oncology at The University of Liverpool and a Consultant in Medical Oncology at The Clatterbridge Cancer Centre NHS Foundation Trust in Liverpool and Dr Sara Meade, a Consultant Oncologist at University Hospitals Birmingham NHS Foundation Trust.

Study Background

HER2 (human epidermal growth factor receptor 2) is a protein that some breast cancer cells express at higher than normal levels that stimulates cancer cell growth. Research has shown [1] that breast cancer spreading to the brain or spinal cord occurs at a higher rate in HER2+ secondary breast cancer patients, compared to other cancer subtypes. Targeted treatments for HER2+ secondary breast cancer do exist and are enabling patients to live longer, but as a result of living longer many of these HER2+ patients are developing brain metastases.   

Brain metastases (or brain mets) can cause a number of symptoms that impact on quality of life including: headaches, nausea or vomiting, changes in vision, seizures, changes in motor function and alterations in mental/psychological well being. In the early stages, brain metastases can be present and not yet cause any of these symptoms.

HER2+ patients who are at higher risk of brain mets could benefit from a screening strategy in which an MRI is used to scan the brain to see if any asymptomatic cancer is present in the brain. Diagnosing brain mets when no symptoms are present is associated with better overall survival than discovering brain metastases after symptoms are present [1].

Brain metastases can be treated with surgery, targeted radiotherapy, whole-brain radiotherapy or combinations of such treatments. Some HER2 targeted treatments can also cross the blood-brain barrier and could also be used in the treatment of HER2+ brain metastases.       

Given the higher risk of HER2+ secondary breast cancer patients developing brain metastases and the impact on lifespan and quality of life, this is an urgent area of unmet need for the community. Research is needed right now to test surveillance strategies that can enable early detection of asymptomatic brain metastases.

Study Aims

The HER2-CNS SURVEILLANCE study is investigating if it is acceptable to women and men with HER2+ secondary breast cancer with no history of brain metastases to be randomised to surveillance via MRI scanning versus no surveillance (the current standard of care). All enrolled patients will have an initial MRI scan to see if brain metastases are present. Patients who are randomised to MRI surveillance will have 6 monthly scans for 1 year.  

This is an initial feasibility study to demonstrate if it is feasible to approach and consent secondary breast cancer into this type of study, perform initial MRI screening and randomise patients to those who receive surveillance or not. Some preliminary data on the frequency at which brain metastases are detected in patients having a brain scan with no symptoms will also be collected. We hope that the HER2-CNS SURVEILLANCE study will lead to a larger study that will explore the benefits of regular MRI brain scanning for detecting brain metastases when no symptoms are present. 

The study team are aiming to recruit 69 patients for the initial MRI brain scan, after which these consented patients will then be randomised to further MRI surveillance or not. The study is recruiting patients from six different cancer centres across the UK (Liverpool, Birmingham, London, Manchester, Edinburgh and Cardiff) and one in The Republic of Ireland (Dublin). The study is anticipated to have a total duration of 36 months.     

Make 2nds Count awarded this funding after an open call and independent external review facilitated by the National Cancer Research Institute.


[1] Darlix et al., Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort. British Journal of Cancer 2019; 121:991–1000. DOI: 10.1038/s41416-019-0619-y