Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer - Episode 2
Insights on diagnosing patients who have HER2+ metastatic breast cancer with brain metastases based on current NCCN Guidelines recommendations when they may present with them during the course of treatment, and the impact on quality of life.
Sarah Sammons, MD: The current NCCN [National Comprehensive Cancer Network] Guidelines in metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer do not recommend a screening MRI. When a patient is diagnosed with metastatic disease, they undergo a biopsy. The guidelines do not say that we should do a baseline MRI of the brain. I can say that some experts do that at baseline given the high incidence of brain metastases in HER2-positive metastatic breast cancer. However, the vast majority of brain metastases are diagnosed based on symptoms, and the current recommendation is to order brain imaging only if a patient has neurological symptoms. Symptoms often include headaches; dizziness; weakness in a unilateral extremity, such as an arm or a leg; numbness or tingling in a unilateral extremity; numbness, tingling, or weakness unilaterally in the face; and slurred speech. Any neurological symptom would lead us to order imaging of the brain. The gold standard would be an MRI of the brain, and that is generally how brain metastases would be diagnosed.
Adam Brufsky did an analysis in 2011 of a large database of patients with metastatic HER2-positive breast cancer, and he and his colleagues asked several questions. When do patients with HER2-positive metastatic breast cancer develop brain metastases? How often do they develop brain metastases? What are some of the risk factors for them to develop brain metastases? What he found was that, on average, the initial metastatic breast cancer brain metastases diagnosis was at about 13 months: 13 months after their initial metastatic diagnosis was the average amount of time that somebody developed a brain metastases. He found that development of brain metastases was associated with younger patients and was also associated with hormone receptor–negative status.
Another clinical trial that would support this quite well would be the standard-of-care first-line clinical trial called the CLEOPATRA trial. This study looked at what is now standard of care in first-line, HER2-positivemetastatic breast cancer with a taxane added to pertuzumab and trastuzumab. What they found was that, with the addition of pertuzumab, there was prolonged progression-free survival and overall survival leading to the standard of care. However, they also found in that study that a patient who developed brain metastases developed a brain metastases at 15 months on average, so it was similar to Brufsky’s 13-month range. We know that 13 to 15 months usually still falls within a patient being on first- or second-line therapy for metastatic disease. The average patient who will develop a brain metastases will develop it earlier on in their course in the first- or second-line settings. That speaks to the need for us to bring blood-brain barrier penetrable agents into earlier lines of treatment for patients who may be at risk for brain metastases.
We know from many retrospective and prospective series that patients with brain metastases have a worse overall prognosis and overall survival than patients who do not have brain metastases. I will say with great hope that this gap seems to be closing in HER2-postitive metastatic breast cancer with the addition of highly active agents, which we’ll talk about later, but I would still say that their survival is less than patients without brain metastases. There is certainly a greater impact on quality of life and health care utilization. We know that patients with breast cancer brain metastases are more likely to be hospitalized, and they are more likely to utilize the health care system.
We know that, for patients who have predominant CNS [central nervous system] disease, their quality of life is severely affected by the brain metastases as well as the subsequent treatments they receive for those brain metastases. Brain metastases can cause an array of neurological complications, depression, anxiety, and decreased quality of life. But the treatments, such as radiation, certainly whole-brain radiation, also come with severely affected quality of life.