Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer - Episode 1

Progression of HER2+ mBC

Sarah Sammons, MD, provides an overview of the progression HER2-positive metastatic breast cancer [mBC] and common areas for the development of metastases, including in the brain.

Sarah Sammons, MD: HER2 [human epidermal growth factor receptor 2]–positive breast cancer 20 or 30 years ago had 1 of the highest risks of spreading distantly and developing metastatic disease. Over the last few decades, given the highly effective HER2-targeted therapies that we’ve had, that has somewhat changed. HER2-positive early stage breast cancer is now 1 of the earliest, most curable breast cancers, given the highly effective therapies that we have.

Patients are generally treated for early stage HER2-positive breast cancer. They’re treated with trastuzumab and sometimes pertuzumab-based chemotherapy. They are then taken to surgery, and based on the KATHERINE data from a few years ago, it has become of the utmost importance to understand whether patients have residual disease at the time of surgery, which means determining whether they have any invasive disease after their HER2-based chemotherapy. If they have residual disease, then we transition them over to trastuzumab emtansine. If they have a complete pathologic response and no residual disease, then we maintain them on their trastuzumab-based therapy for a year. With this most up-to-date treatment regimen, even in the highest-risk early stage breast cancer patients, about 88% will not have any disease come back at 3 years, which is tremendous.

That certainly does leave a small portion of patients with high-risk, early-stage disease who progress and become metastatic. A large portion of the metastatic HER2-positive population has what we call de novo metastatic disease. Their early stage disease is not caught soon enough, and by the time their disease is diagnosed, they already have metastatic disease, which is disease that has spread beyond the breast and regional lymph nodes.

Usually in HER2-positive metastatic breast cancer, common places of spread include the liver, lung, bones, lymph nodes, and unfortunately the brain. Even with the highly effective HER2-targeted early stage breast cancer agents that we have–trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine]—of the patients who progress to become metastatic, about 50% will progress in the brain as their first site of metastatic disease. We’ll talk more later about why that might be, but certainly brain metastasis and progression to metastatic disease in the brain is still a large problem in early and late-stage HER2-positive breast cancer.