Case 3: Selecting Therapy For HER2+ Breast Cancer With Brain Metastases


Centering discussion on a patient case of HER2+ breast cancer with brain metastases, experts consider optimal treatment regimens in this setting.


Sara A. Hurvitz, MD: Let’s go on to our third and final case, which is relating to a patient who does have brain metastases and HER2 [human epidermal growth factor receptor 2]–positive disease. We have a 62-year-old woman who presents with a palpable 3.5-cm mass in her right breast, in her right upper quadrant, in her axilla. A core needle biopsy of both areas demonstrates grade 3 IDC [invasive ductal carcinoma], ER [estrogen receptor]–negative, PR-negative, HER2+. Imaging shows a 3.1-cm lesion in the breast, with multiple axillary lymph nodes and 3 lesions in the right lung. Again: de novo metastases. Brain MRI is negative at the baseline. A biopsy of the lung does confirm the same: HER2+ disease. Her performance status is outstanding. She initiates THP [docetaxel, trastuzumab, pertuzumab] for 6 cycles, then goes on to maintenance HP [trastuzumab, pertuzumab]. She’s had a CR [complete response] in the breast mass axilla and lung metastases—a very good outcome. Before I go on to the next slide, are either of you doing brain imaging in patients at their first diagnosis of metastatic disease if they don’t have neurological symptoms?

Sara M. Tolaney, MD, MPH: Outside a clinical trial, no, we haven’t been. In general, I’ve been scanning with symptoms, but there are a lot of trials ongoing. We have a trial looking to see if screening for brain metastases could have potential benefit. In this case, a trial is designed to see if it will help prevent neurological symptoms by finding those lesions early and potentially intervening early. It’s an excellent question, and it’s unclear what the right answer is here.

William J. Gradishar, MD: I will just say ditto.

Sara A. Hurvitz, MD: Eighteen months later, she progresses in the lung with 2 new lesions, and she’s been developing regular headaches for the past month or so. At that time she undergoes a brain MRI, which showed 3 brain lesions, the largest being 1.1 cm. The question becomes, how do we treat now? What do we do for this patient? Before we go into what she had, Bill, how would you approach clinical decision-making in this patient?

William J. Gradishar, MD: Clearly, this patient’s course of therapy needs to change. This morning I saw somebody who had 17 brain metastases treated with SRS [stereotactic radiosurgery]. You wouldn’t have thought beyond 1 or 2 in the old days, but now the sky is the limit. That said, this patient would be considered for SRS. We would try to hold off on whole-brain radiation therapy for these downstream consequences of that for as long as we could. This is a patient with active lung disease, so something going on below the neck and in the head might make the HER2CLIMB regimen more attractive. If she got SRS for whatever reason, T-DXd [trastuzumab deruxtecan] could still be a consideration; it’s not an absolute if SRS is done.

Sara A. Hurvitz, MD: Let me push you on that a little, Bill. If she came to you and said, “I don’t want to do radiation at this point. Is there any way I can switch my therapy and follow the brain?” Is this the type of patient for whom you’d consider treating her just the change in systemic therapy and initiating tucatinib-based treatment?

William J. Gradishar, MD: If that were the scenario and the patient was adamant—“I don’t want radiation. I want everything upstairs intact. I want no diminution in my cognitive function, and it’s an absolute—then the most compelling data, particularly for active brain metastases in the HER2CLIMB regimen, are with tucatinib. The data are more compelling based on what we have for tucatinib-based regimens for active brain metastases than T-DXd [trastuzumab deruxtecan].

Sara A. Hurvitz, MD: Sara, would you suggest she had SRS and then change her therapy? Or would you suggest just changing therapy in this type of patient?

Sara M. Tolaney, MD, MPH: It’s tricky. It would be a discussion with the neuroradiation oncologist to understand how easy it is to SRS all lesions, how big each 1 is, or how much peritumoral edema is there. You’d want to understand the case in detail to make that decision. In general, I tend to want to SRS the lesions and move on to systemic therapy. It makes me feel as though I’ve got them controlled and I can move on. I tend to want to avoid whole-brain radiation because there are more neurocognitive effects there. If I had an alternative, I’d try tucatinib. In this case, you could have gone either way. If you’re going to do SRS anyway, you could have SRS and gone to T-DXd [trastuzumab deruxtecan] or potentially to tucatinib.

Sara A. Hurvitz, MD: Multidisciplinary team gets involved as soon as we see brain metastases develop. You’ve both made good points about involving them in the decision-making. I want to change the scenario a little. Bill, let’s assume her lung is perfectly controlled. She’s progressed in the brain, and she’s on HP [trastuzumab, pertuzumab] maintenance. What are your thoughts about changing systemic therapy if the extracranial disease is controlled and her disease is progressing in the brain only?

William J. Gradishar, MD: This is a tough question because if her systemic disease has been stable for an extended period, I still may approach this patient with SRS and watch carefully for things going on below the neck. I don’t know that I’d absolutely change therapy in that kind of patient. That’s how I’d approach it, but it’s a bit of an unknown. This could be a patient for whom you maintain the current systemic therapy: treat the brain, and watch.

One other thing: when we were talking about ILD [interstitial lung disease] and T-DXd [trastuzumab deruxtecan]. From a compliance standpoint, you have to assess the patient with respect to 3 drugs. The trastuzumab we’re giving to them, but capecitabine and tucatinib are oral medications that you must be confident the patient is taking appropriately.

Sara A. Hurvitz, MD: Taking 1 continuously and taking 1 for 14 days on, 7 days off so it becomes a lot more complex. That’s a great point.

Transcript edited for clarity.

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