In a new trial, Sunnybrook researchers are exploring the use of focused ultrasound (FUS) to open the blood-brain barrier (BBB) and enhance the delivery of chemotherapy drug Herceptin to HER2+ breast cancer that has spread to the brain.
Metastatic breast cancer is cancer that starts in the breast and then spreads beyond the breast to areas like the bone, liver or other organs, and brain. There is currently no treatment that can completely cure metastatic breast cancer, also known as Stage IV breast cancer.
Treatments for management of the disease include hormone therapy and chemotherapy.
About 5 to 10 per cent of newly diagnosed breast cancers are metastatic. Women facing metastatic breast cancer have a median survival of two years, according to It’s About mBC Time, an organization dedicated to raising awareness of metastatic breast cancer.
Dr. Nir Lipsman, neurosurgeon and researcher, explains the challenges of treating breast cancer that has spread to the brain, and what he hopes this new FUS trial will accomplish:
What is this focused ultrasound (FUS) trial looking at?
This is a phase 1 trial, meaning we are looking at the safety of using FUS to open the BBB in patients with breast cancer that has spread to the brain. We want to ensure that the BBB closes after it is opened, and that there are not adverse effects of opening it up.
What is the blood-brain barrier (BBB)?
The BBB is a physical barrier that protects the brain. It’s invisible to the naked eye and is made up of cells that work together to prevent toxins from getting passed through the barrier and into the brain. In many ways, that’s a good thing because it stops dangerous things from reaching our brains. But, it also stops medications like chemotherapy from reaching tumours, where they are needed most.
How does this trial work?
For FUS, we use a helmet-like device, containing over 1,000 individual transducers (which convert electrical energy into sound energy), to converge ultrasound waves on to discrete points in the brain. The idea is to temporarily open the BBB to allow the passage of chemotherapy to regions surrounding the tumour.
Patients in this trial will wear this special helmet and go inside an MRI that helps target the specific area of the brain where FUS is directed to temporarily open the BBB.
Our trial participants will be given Herceptin, a chemotherapy drug that is used to treat both early stage and metastatic breast cancer. The drug typically does not cross fully the blood brain barrier, so it is our hope that by opening the BBB, we can better deliver Herceptin straight to the tumour.
The participants will receive MRIs after 24 hours, one month and three months, to see if there was any affect on tumour growth, as well as other cognitive functioning tests to see how the treatments are being tolerated.
For the first phase of the trial, patients will be undergoing a single FUS BBB opening session with Herceptin. We are in the process of expanding this to up to 6 treatments with a combination of chemotherapies to see if this is safe and effective in patients with Her2+ breast tumours spread to the brain.
Why is metastatic breast cancer in the brain so hard to treat?
The BBB makes it difficult for potentially effective treatments, such as Herceptin, to cross and target breast tumour cells in the brain. Herceptin is a large compound, several thousand times larger than the typical compound that can bass through the BBB. FUS offers the potential to temporarily open the BBB permitting Herceptin in to the brain in larger concentrations.
Trial participants (so far we have recruited three) will have a single chemotherapy treatment together with FUS BBB opening, and we are currently in the process of expanding this to up to 6 treatments. We are especially interested in whether opening the BBB repeatedly, over several months, is safe and well tolerated by patients, and whether there is any effect on tumour growth or progression.Learn more about the Focused Ultrasound Foundation