Patient Profile 3: Metastatic HER2+ BC


Dr Kaklamani presents a profile of a patient with HER2+ breast cancer and liver metastases who had disease progression after first-line chemotherapy and a solitary new brain metastasis after second-line T-DM1.


Sara Hurvitz, MD: Now we’re going to go through a case of metastatic breast cancer. For that, Virginia, take us through.

Virginia G. Kaklamani, MD, DSc: Sure. This was a 49-year-old woman who presented with a large breast mass and positive axillary nodes. I staged her and she was found to have liver metastases at the time of a diagnosis of de novo metastatic disease. She didn’t have any bone metastases when we treated her, and she was HER2 positive.

We gave her the initial CLEOPATRA regimen with docetaxel. She had a great response for a long time. At 22 months after initiation of treatment she was found to have progression of disease with her liver metastases. And so, the question then was, what do we do? So we gave her T-DM1 [trastuzumab emtansine] a little while ago, she had 12 months of progression-free interval, and at that point she started complaining of a headache.

I don’t typically do MRIs [magnetic resonance imaging] for asymptomatic patients so I had not been doing those, but obviously when she [reported] a headache I did do an MRI. She was found to have a 2.5-cm frontal lobe lesion, but her systemic disease was stable. So the question here was, what do we do with this patient?

Sara Hurvitz, MD: Well, again, this is something we encounter, unfortunately, in practice. Earlier Heather mentioned this potential for screening patients for brain metastases who are asymptomatic. So based on that, Melinda [and] Debu, are you doing brain imaging in your asymptomatic patients? If you are, at what intervals? Melinda.

Melinda L. Telli, MD: I am not. Only if they have symptoms.

Debu Tripathy, MD: I don’t routinely do it. A lot of my patients ask me about it, and I tell them that at the current time we don’t have any basis to do it. We might be overtreating patients if we diagnose [when they’re] asymptomatic. I do tell my patients that my threshold is very low and if they were to come and tell me that they had anything that sounded like a CNS [central nervous system] symptom, I would go ahead and scan them. And some of my patients take advantage of that and get scans because they had a moment of dizziness. But I just want to emphasize that this is something we should formally study, and there are some plans to get a consortium together to actually do this.

Sara Hurvitz, MD: And Heather, are you routinely doing it in asymptomatic patients, or is it patient by patient?

Heather McArthur, MD: I’m not doing it routinely, but I do wonder whether I should be. But I haven’t pivoted yet and changed my practice. And I guess until we actually demonstrate that surveillance and earlier detection informs a clinical pivot that actually improves clinically meaningful outcomes, I probably won’t change that practice.

Sara Hurvitz, MD: I agree with you. So what would you do in this situation? It sounds like everything below the neck was stable, right? Systemic disease was not progressing. So what would you do, Heather?

Heather McArthur, MD: This is another really challenging real-world question because I would potentially be tempted to continue T-DM1 for this patient and refer them for radiation. HER2CLIMB was very bold in enrolling all of those patients with active brain metastasis, so I would think about the HER2CLIMB regimen. But also given the non-CNS disease control, I would wonder whether I would just save that for a later date when I had more global disease to attend to.

Sara Hurvitz, MD: Yes, and with HER2CLIMB, I think …if the lesion in the brain was greater than 2 cm, or patients were highly symptomatic or needed steroids, they weren’t eligible to go on. And the one thing I’m thinking of, there are some retrospective analyses suggesting T-DM1–treated patients who have stereotactic radiosurgery [SRS] may have a higher rate of radiation necrosis. This hasn’t been formally validated, but…I’m seeing so much radiation necrosis now, it’s a downside of radiation. How would you address this patient, Melinda?

Melinda L. Telli, MD: I think in the past, my approach would have been to send her for local therapy to the brain and to continue the T-DM1. In this case, it’s just a solitary lesion. Of course, [for] some of these patients it starts with a solitary lesion, we treat them, and then a few months later there are multiple lesions. And so we don’t know. Sometimes we treat that one and then that’s it. Potentially she could continue to derive benefit from T-DM1 so it is a difficult situation.

In the past, I would have just treated continued the T-DM1, but [now] I would think about the tucatinib-based therapy in this setting, whether you start it right at this point or treat the brain, get an additional restaging [done], and then make a decision. If there are new things coming up, then definitely switch to tucatinib. It’s a challenge; we don’t want to move through the therapies too quickly. While we do have therapies we can switch to, the question is always, should we move on to something new?

Sara Hurvitz, MD: What about you, Debu?

Debu Tripathy, MD: I think this patient needs local therapy. They’re symptomatic. It’s a 2.5-cm lesion. At our center it would be a toss-up between excising and then radiating using SRS to the bed vs just SRS. I think it probably needs to be resected. And remember, there are data [showing] that resection and radiation are superior [to] radiation alone. So that’s what I would do.

Sara Hurvitz, MD: So you do that. Would you then continue T-DM1, or would you switch to systemic therapy?

Debu Tripathy, MD: At this point I’d continue the T-DM1 and close follow-up. The kind of patient that I’d want to start is someone probably in later lines of therapy who has multiple small lesions but too many to treat with SRS. And you really want to avoid whole-brain. That’s what would drive me to use systemic therapy, if the other option is whole-brain radiation.

Sara Hurvitz, MD: So [Virginia], how did you think through this, and what did you do?

Virginia G. Kaklamani, MD, DSc: Thankfully there’s a multidisciplinary team that helps all of us, including the neurosurgeons and the radiation oncologist. So I sent her to both. They resected the tumor. It was easily resectable, and I’m so impressed by the fact that they enter the brain, and the next day, the patient has zero symptoms and is out of the hospital. It’s just amazing what these [doctors] do. So we did that, and in many of these cases, they actually don’t do SRS in the bed, they just wait and then if they’re progressing, then they will do SRS. So I typically leave those decisions to them. I did continue T-DM1. I like continuing an agent for as long as I can, especially if the systemic disease is stable. At the same time, we have data with tucatinib that shows delay of a second event. And so this always is a question for me, am I doing the right thing?

Sara Hurvitz, MD: Amazing case, amazing discussion. Very data-driven in many situations where we don’t have a lot of data. I love how you all think through these. This has been a great discussion.

Transcript edited for clarity.

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