Case 2: Relapsed/Refractory HR-/HER2+ Breast Cancer


Komal Jhaveri, MD, FACP: This patient is a young, 39-year-old woman who presented with a 4½-cm mass in her left breast, and at the time of presentation, she was also found to have 3 palpable axillary lymph nodes. A core biopsy that was performed from the left breast mass confirmed to be invasive ductal carcinoma that was ER/PR [estrogen receptor/progesterone receptor] negative and HER2/3 [human epidermal growth factor receptor 2/3] positive by immunohistochemical staining. Systemic staging that was performed revealed 3 liver lesions, the largest of which measured 3 cm.

Ruta Rao, MD: What are your next steps in taking care of this patient? Particularly, would you biopsy the liver?

Komal Jhaveri, MD, FACP: Yes. Our practice [at Memorial Sloan Kettering Cancer Center] has been to biopsy the first metastatic site, especially when there is a suspicion based on systemic imaging. For a majority of our patients, we do that to confirm the receptor status, and it remains the same in the primary and the metastatic sites. For 14% to 15% of our patients, we have seen discordance in the receptor status. These are some of the main reasons: First, to confirm that this is metastatic disease and that we’re treating the patient appropriately for that, and second, to confirm that we’re treating them for the right disease that we thought we were dealing with.

Ruta Rao, MD: Thank you. Dr Sadimin, do you want to comment on concordance between the primary site and the metastatic site with hormone receptors as well as HER2?

Evita Sadimin, MD: Yes. We do generally test the initial site if we have them and in the metastatic sites. In a majority of cases it would be the same. But as mentioned, some cases would be different. It’s a team approach in terms of how to treat the patient.

Ruta Rao, MD: Dr Jhaveri, would you consider ordering a baseline brain MRI for this patient in doing your initial work-up?

Komal Jhaveri, MD, FACP: That is an interesting question, and it is even more relevant given the approvals that we’ve had for our patients in the metastatic setting with newer agents in 2020. The current guidelines and the track that we follow for these patients is that we don’t reflexively order screening-brain MRIs. We do systemic staging, but we order brain MRIs only if there’s a suspicion for brain involvement with some neurological deficit or some other symptom that the patient presents with. This is an active area of research for which there are ongoing trials trying to address the question of what the incidence would be and how we can prevent neurological deficits by catching brain lesions earlier for patients, specifically those with HER2-positive and triple-negative breast cancer. It is something we might see evolve and change in the near future, but in 2020, I am not ordering screening-brain MRIs for my patients.

Ruta Rao, MD: Thank you. Dr Tolaney, what about you? It’s off-trial, but would you order a baseline brain MRI?

Sara Tolaney, MD, MPH: I have started discussing it with patients more recently. I was a hard no on that; it wasn’t in the guidelines. We were supposed to do it only with symptomatic neurologic symptoms to get MRIs, but the incidence is so high in HER2-positive disease: 50% of people end up with brain metastases. We now have approval, as Dr Jhaveri was alluding to, for using tucatinib that can result in a survival benefit for patients with brain metastases. As Dr Jhaveri noted, we don’t have any robust data to suggest that screening itself would improve survival or prevent neurological symptoms, but there are trials that are ongoing trying to address this.

At our institution [Dana-Farber Cancer Institute], for example, we have a trial in which we are screening patients up front, and with each subsequent restaging with an abbreviated brain MRI, we are seeing if that will prevent onset of neurological symptoms sooner than someone who wasn’t getting screening MRIs. As Dr Jhaveri alluded to, there’s going to be more to come with this, and we’ll get more data. Our threshold has changed dramatically because we now have agents available that can improve survival for patients with brain metastases.

It’s something to discuss with patients. A lot of patients have trouble getting brain MRIs, so it’s not the easiest thing if you’re claustrophobic and so forth. I mention it to patients, and I have offered it. It obviously also depends on whether insurance will pay for it because they will sometimes deny it if the patient is asymptomatic.

Transcript edited for clarity.

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