HER2+ Metastatic Breast Cancer: Role of Radiation Therapy in Managing CNS Disease


Expert perspectives on the respective role of radiation therapy to manage brain metastases in the setting of HER2+ breast cancer.


Sara Tolaney, MD: Well, that’s super helpful. I think you’re exactly right. We do phone a friend. Thankfully, we have a friend here, Ayal, who is an expert on this. As you know, we do call you all the time for these questions in clinic, and we do appreciate it. I think what we struggle with is how do we make a decision about who’s a candidate for SRS [stereotactic radiosurgery] and who needs to really get whole brain radiation. How do you make these decisions when you’re seeing patients?

Ayal Aizer, MD: It’s a great, great question. I think the first thing we always ask is do we need radiation? Because both SRS and whole-brain [radiation therapy] can have some toxicities. That requires us to rely on your guidance as to what the viable systemic therapies are for a given patient. Thankfully, in the HER2 realm, there’s much more available and much more effective options than in other subtypes of breast cancer for intracranial management, which is always really nice to see. So, we’re often interdigitating radiation with a systemic approach and thinking about the long-term plan for a given patient.

When it comes to deciding with SRS vs whole brain, there have been a number of randomized trials on this topic. They included patients of many different primaries, so lung cancer, breast cancer, and melanoma. Those studies generally told us that whole-brain radiation, although it lowers the likelihood that a new tumor will develop, doesn’t tend to improve survival, and it is associated with decreases in quality of life and neurocognitive function. The one catch with those studies is that they typically capped the number of tumors that were eligible for enrollment. So, some studies included 1 brain tumor, some up to 3, some up to 4. There’s very early data for more than that. Thankfully we’re going to have in the next few years, 3 additional randomized studies published, going up to 15 or 20 tumors hopefully. Then we’ll really have a better answer.

In addition to the number of tumors, we’re also thinking how quickly new tumors are showing up. It’s different if there are 6 tumors that showed up relative to a scan that was a month and a half ago vs 6 that developed over the course of a year. The size and symptomatology can impact this decision and how urgently we need to start radiation. Whole brain radiation can start instantaneously. SRS takes at least a few days, typically, to arrange. So, thankfully, in breast cancer, we often have that time window. That’s another thing that goes into our thinking.

We know that whole brain radiation has a lot of [adverse] effects, both in the short and long term that are impactful, and I think the field is certainly moving towards more and more SRS, which is probably a good thing. I think the question is how far we push. For example, if a patient comes in with 12 to 15 metastases that have some decent size to them. We know at some point, if the patient lives long enough, there’s a decent chance that there’ll be radiation necrosis somewhere. These are really tough questions, and we need more data. Thankfully, within a few years, we should have more data.

Sara Tolaney, MD: That’s great to hear that more data is coming because it is such a challenging question.

Transcript edited for clarity.

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