10/21/2025
This lab investigates breast cancer brain metastasis by following how cancer travels and changes across the body
Breast cancer involves a full network of cancerous and healthy cells that live and work together, far beyond an initial bump or tumor. When breast cancer spreads to the brain – called breast cancer brain metastasis (BCBM) – that complex network makes it especially difficult to treat, turning an already serious diagnosis into one of the most challenging forms of the disease.
"This stage of breast cancer is one of the most challenging forms of the disease, and developing treatment strategies requires us to investigate beyond the breast,” explains Cleveland Clinic’s Peiwen Chen, PhD. “We need a deeper understanding of the brain itself, and of our immune systems. We need a deeper understanding of how cancer behaves as part of a microenvironment within these larger systems.”
Dr. Chen and Fatima Khan, PhD, a senior researcher in the Peiwen Chen Lab, discussed their lab’s latest breast cancer breakthroughs that reshape how we think about and treat metastatic breast cancer.
What is breast cancer brain metastasis?
Breast cancer brain metastasis describes the process where cancer cells from breast tumors spread to the brain and form brain tumors. It also describes the brain tumors that are formed, differentiating them from when the cancer started in the brain.
The speed that breast cancer can metastasize to the brain, and how common that phenomenon is, depends on the genetic mutations in the breast tumor. Up to 30–50% of individuals with HER2-positive breast cancer might develop brain tumors. For triple-negative breast cancer, it’s closer to 20%.
No matter what type of breast cancer, when that cancer reaches the brain, the prognosis becomes more dire. And until recently, this type of cancer has been understudied and undertreated.
Why does breast cancer brain metastasis need its own research strategy?
Put simply, BCBM needs its own research strategy because it needs its own treatment strategy.
“Once breast cancer spreads to the brain, it’s not just breast cancer anymore. The tumor adapts to its new environment," Dr. Chen explains.
“The brain is a fortress,” Dr. Khan says. “The blood-brain barrier makes it hard for drugs to reach tumors. And the immune system behaves differently here. You can’t just apply the same treatments used for primary breast cancer, because a lot of those treatments involve the immune system.”
Dr. Chen’s lab is working to understand the brain’s unique immune environment: how cancer cells and healthy cells interact and influence one another. Their recent breakthroughs in breast cancer brain metastasis reveal that brain-resident immune cells aren’t just bystanders; they’re active participants in helping cancer spread.
Taking a whole-body approach to breast cancer breakthroughs
Dr. Khan’s previous work in primary breast cancer research and Dr. Chen’s expertise in glioblastoma lets them approach BCBM from both ends of the disease.
In preclinical models, the Chen Lab showed that FDA-approved canker sore medications can stop immune cells in our brain from helping breast cancer brain metastasis. The medication works because it also blocks brain-resident immune cells from making signaling molecules called TBK1, which helps cancer cells colonize the brain.
“We’re not targeting brain tumor cells directly,” Dr. Khan explains. “We’re educating the immune cells to help reduce tumor invasion and metastasis.”
The team is already in discussions with Cleveland Clinic’s Brain Tumor Center to design clinical trials targeting TBK1.
“We’re learning that the key to stopping breast cancer brain metastasis isn’t just about attacking the tumor,” Dr. Chen says. “It’s about the entire ecosystem they live in. And if we can change that ecosystem, we can change the outcome.”
