Management of CNS Metastases in R/R HER2+ mBC


Sarah A. Hurvitz, MD: HER2-positive breast cancer is a unique subtype. Generally the way we look at breast cancer as a whole is, we generally group them based on expression of receptors. There is hormone receptor-positive breast cancer, HER2-positive breast cancer—which can have hormone receptor coexpressions, 50% to 60% of the cases—and then there is triple-negative breast cancer, which lacks hormone receptor expression as well as HER2.

HER2 breast cancer is unique not only in its aggressive behavior, but also the fact that even though we have a lot of successes in the metastatic setting for the treatment of it with HER2-targeted therapy, patients still have their disease progress. We need new therapies to treat this disease.

Another unique unmet need and challenge in the management of HER2-positive metastatic breast cancer is the occurrence of CNS [central nervous system] metastases, both in the brain parenchyma, and then an even worse challenge to manage is leptomeningeal carcinomatosis.

Up to 50% of women with HER2-positive metastatic breast cancer will develop central nervous system metastases. This is an area that’s a huge unmet need because many of our molecules can’t traverse that blood-brain barrier and manage or improve outcomes within the brain for this complication.

When you compare the incidence rates of CNS metastases in HER2-positive breast cancer to that in hormone receptor-positive HER2-negative, hormone receptor-positive breast cancer has a lower incidence overall. It does happen, but it tends to be later in the course of the disease. Of course, triple-negative breast cancer has its own unmet need because it, too, has a higher risk of CNS metastases.

The current management for CNS metastases is primarily local regional therapy, which means whole brain radiation, stereotactic radiation, and sometimes surgical resection. These can be associated with a lot of morbidities for patients, and certainly can’t be repeated in perpetuity for patients who have recurrences in the brain. It is so important for us to identify and develop molecules that patients can take as pills or intravenously that cross that blood-brain barrier and impact the control of disease within the central nervous system.

Transcript Edited for Clarity

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