Zeroing in on Druggable Targets for Metastatic Breast Cancer
Bonni Lee Guerin, MD
Breast cancer is the second most common type of cancer to metastasize to the brain. In fact, 20 percent of women with metastatic breast cancer will ultimately develop central nervous system metastases. In the HER2-positive subset, that number is closer to 40 or 50 percent. Thankfully, targeted therapies are driving major advances in treatment and improving life expectancy from a number of months to a number of years. Oncologist and Director of the Breast Cancer Treatment and Prevention Program at Overlook Medical Center Bonni Lee Guerin, MD, shares the latest.
How does genetic sequencing factor into breast cancer care?
Over the past decade, breast cancer treatment has undergone massive changes – particularly in the area of medical oncology thanks to advances in genetic sequencing. Historically we would separate breast cancers into two categories, slower-growing estrogen-positive breast cancers and faster-growing estrogen-negative breast cancers. With the ability to take a deeper dive into the genetic makeup of individual cancers, we are now able to not just look at what category into which they fall, but actually give these tumors signatures or fingerprints. This plays a significant role in steering how we deliver personalized care.
How is genetic knowledge being used to treat metastatic breast cancer in the brain?
Oncology has been getting better from the neck down. We can control disease in the lungs or liver, for example, because we have new treatments that can get to these places through free exposure in the bloodstream. The painful irony is that cancer patients are now living long enough to develop metastases in the brain.
In this regard, the challenge is getting beyond the blood-brain barrier. The trick is using the genetic information we now have about the specific cancer types to our advantage and finding breakthrough therapies that can deliver targeted drugs across that barrier. This is particularly important for people with HER2-positive breast cancer, which has an inordinate predilection to metastasize in the brain.
What are the latest drugs being used to treat breast cancer brain metastases?
There are two drugs in particular worth talking about in the HER2-positive space. The first is ENHERTU, which is an antibody and chemotherapy connected to each other. At the tail end of the antibody is a powerful chemotherapy. When connected to the antibody, it acts like a guided missile that can pass the blood-brain barrier. It can hunt out and latch onto the HER2-positive cells in the brain and then releases the chemotherapy. Clinical studies have shown a 60 percent success rate with ENHERTU and this Trojan Horse approach.
Tucatnib is another fascinating drug that works in a different way. Tucatnib interferes with the unique signals that cancer cells use to grow. In studies, patients who received Tucatnib as a pill as part of their treatment lived an average of 20 months compared to 11 months for those who did not receive the drug. That is still not enough time, but with new therapies continually being developed, it may be enough time to get them to an even more effective treatment.