Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer - Episode 3

Monitoring Brain Mets in HER2+ mBC

Kevin M. Kalinsky, MD, MS, discusses monitoring patients with HER2-positive mBC who have asymptomatic brain metastases and advancements in therapy for HER2-positive disease leading to increased brain metastases.

Kevin M. Kalinsky, MD, MS: Brain metastasis is a real issue in our patients with breast cancer, particularly for some subtests of breast cancer, including HER2 [human epidermal growth factor receptor 2]–negative and HER2-positive disease.

One of the things we’ve seen with HER2-positive metastatic breast cancer is that, while patients may not have brain metastases at the time that they have metastatic disease, it might ultimately occur. There are descriptions that it can occur for up to 50% of patients. As opposed to when they get breast cancer, where we can see the tropism is a little earlier. One of the issues we’re facing is that, as our drugs get better and offer better systemic control, then patients may have asymptomatic CNS [central nervous system] metastases.

The exact rate is hard to describe. However, this is something that comes up in our tumor board [at the Columbia University Irving Medical Center] on a regular basis. In particular, for those patients who have newly metastatic disease, we determine whether we should be doing brain MRIs on those patients. There are some data that have been published that have documented that patients can have asymptomatic brain metastases at that time. The guidelines do not recommend doing that, and every institution may have a different approach. At our institution, it’s not something we commonly do in the absence of brain metastases. However, this is going to be an increasing issue given the fact that we have better therapeutics to keep the disease under control in the body.

One of the advantages of treating patients with HER2-positivemetastatic breast cancer is that we have a number of agents. There was a landscape change when we started to utilize trastuzumab. Think about all the leaps and bounds in terms of the therapies that have been able to treat our patients. Other monoclonal antibodies, like pertuzumab, the antibody drug conjugate T-DM1 [trastuzumab emtansine], and more recently trastuzumab deruxtecan. We have a number of small molecules as well as tyrosine kinase inhibitors.

The issue is that not all those drugs have great CNS penetration. We know that these smaller molecules, the tyrosine kinase inhibitors, have good CNS activity, but it’s not so clear for some of the larger molecules. On the 1 hand, you can get great systemic response with these monoclonal antibodies. In terms of crossing into the blood-brain barrier and treating the CNS, it’s a real issue. It’s also an issue for our patients with early stage breast cancer when we’re treating with agents, and we’re hoping to decrease the likelihood of developing metastases, including CNS metastases. It’s important to think about agents that may prevent CNS disease or keep it under control.

When we’re talking with patients in our clinic, it’s important to make sure that we’re asking about whether anybody is having any neurological symptoms. This is 1 thing that sometimes comes up with my patients when they’re getting screen imaging, and they’re not having their CNS-related adverse effects: whether they should have brain imaging even though it’s not within the guidelines. When a patient is really worried, I’ll have a discussion with the patient on a 1-to-1 basis about whether we should get a good baseline brain image. In terms of screening for the brain, if one has a large CNS metastasis, we can see this with a head CT scan. Our radiologists often recommend doing brain MRIs, which can be beneficial at looking at the parenchyma and looking for evidence: the presence or absence of leptomeningeal metastasis.

If we have a concern about whether a patient has a brain metastasis and there are no contraindications for getting a brain MRI, the insurance company will pay for it, so that’s often the test that we will select.

When we treat patients with CNS metastasis, there can be a range of symptoms that we can see. It can sometimes present with some more mild symptoms where patients may, for instance, have some headaches or not quite feel themselves. It can then be a bit more extreme, where patients are having seizures, weakness, sensory loss, or any associated cranial abnormalities that develop. When patients get a CNS disease, it can range from having a few small brain metastases to having innumerable brain metastases. When we get really concerned is when patients have leptomeningeal disease because that particular disease portends a poor prognosis, unfortunately.

When we were treating patients with CNS metastasis with a limited burden, and we’re able to get some local therapy and keep that under control, it doesn’t necessarily affect adherence and cognition. However, we get concerned when patients have a higher burden of disease, whether that is because of the amount of disease that they have or because of the treatment we’re giving, such as whole-brain radiotherapy. With patients who have a good amount of CNS parenchymal brain disease, while we often treat those patients with whole-brain radiotherapy, the real concern is that patients can have acute and more late effects of toxicity from whole-brain radiotherapy that can affect patients’ memory, and they can become increasingly forgetful. It can be hard to treat the patient, and it can be hard for the family to help manage that patient.