Molecular Testing in Relapsed/Refractory HR+ Metastatic Breast Cancer


A brief review of the role molecular profiling plays at a patient’s relapse with HR+ metastatic breast cancer.

Aditya Bardia, MD, MPH:
For ER [estrogen receptor]–positive metastatic breast cancer, let’s move to second-line [therapy]. Let’s say this patient has disease progression after 2½ years. Michelle, do you recommend we do repeat biopsy? What’s your impression of tissue vs liquid biopsy in this setting?

S. Michelle Shiller, DO, AP/CP, MGP: In keeping with prior discussion, I recommend repeat testing upon each progression, especially when therapies are being administered because that’s going to change the molecular biology of the tumor. We have documented changing things such as HER2 [human epidermal growth factor receptor 2] status. There are also mutations in the background that we may see…. The other advantage in time is that you may also have FDA approvals that have come to the marketplace. There are multiple reasons to repeat that depending on that window between second and third line.

With respect to the specimen approach, liquid biopsy is coming of age, and it’s going to change the management of our patients with cancer. In this setting, there’s greater likelihood that you’re going to have a positive finding than if you were in earlier-stage disease because you have a more significant tumor burden. The other thing that we’re seeing in the data is that those in circulation are the ones most likely driving the disease process, and so it will help you to establish a therapeutic approach that may be more effective at getting the disease more localized and better controlled. Having said that, the technology is newer. If that’s not informative or significantly conflicting with the historic prior-tumor testing, it might be advisable to get also a piece of tissue if feasible to compare it. If it’s negative, we definitely would do that.

To summarize all that, it’s important to note that you can’t predict whether you’ll detect something on liquid. When these patients are progressing, our windows can get tighter. They may be getting sicker, more tired. It might be advisable to order both simultaneously. Depending on the turnaround time of the assay, you may be able to stop that tumor test. If the result comes back quickly and is part of that tumor test advancing, [it may be] so far in the process that you can’t stop it. That way, you make sure you’re sensitive to the time for the patient with respect to when the results would be received to guide your clinical decision.

Aditya Bardia, MD, MPH: That time period is critical as well. One advantage with plasma-based genotyping is that it’s more convenient for patients. It’s blood draw compared with biopsy. But in ER+ setting, patients sometimes have bone metastases. It’s good to have this option as well.

Transcript edited for clarity.

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