PracticeUpdate Oncology February 2019

SABCS 2018 25

Dr. Haffizulla: Can you back track a little bit and tell us about how the circulating ESR1 mutation is detected? Dr. Gradishar: Sure. So, how they detect it, I mean there’s two ways of doing it. You can get tissue, which is invasive, but now, again, in the era of circulating tumor DNA analysis, we were able to look at samples that had been obtained from the patients when they were enrolled in the trial. So, obviously taking a blood sample is far less invasive; easy. It’s something that theoretically you could do sequen- tially in a given patient over time and you could see the evolution of the disease. So, it becomes a much more attractive way of, in real time, monitoring what’s going on in the tumor. Dr. Haffizulla: How could the results of this study actually be used to influence practice decisions? Dr.Gradishar: Well, I think the thing that’s…its proof of principle and val- idating that in patients who get aromatase inhibitors, ESR mutations are quite common. We’ve known from other trials that if you look at a de novo population of people withmetastatic disease not exposed to an endocrine agent, ESRmutations are quite infrequent. Whereas, under pressure or with exposure to aromatase inhibitors in the adju- vant setting, in the metastatic setting, the probability of having an ESR mutation goes up. If you have ESR mutations, the likelihood of responding to an aromatase inhibitor is less and it makes other strat- egies more attractive. So, that may be a way of helping define the optimal therapy in any given patient. Dr. Haffizulla: Any final details you’d like to share on this particu- lar study for our viewership? Dr. Gradishar: No. I think this is one of many trials that have looked at circulating tumor DNA as a potential tool that we all have avail- able we can order this now. And I think just because we can order things doesn’t mean we should order them. We have to know what we’re going to do with the information when we get it. And although what we do with it is still relatively limited today, I antici- pate as we go forward the mutations we find are going to help us select therapies that we use in patients.

likelihood of benefiting from any therapy was diminished. And cer- tainly, with ESR being present, there was a differential between the PFS for those who had it and who did not have an estrogen receptor mutation present. So, I think what this tells us, again, it’s not going to change anything we do, but number one, it tells us that when you’re exposed to aromatase inhibitors the probabil- ity of having an estrogen receptor mutation is higher and it really speaks to the notion of doing precision medicine as a guide to therapies that we may have now and in the future.

Go to www.practiceupdate.com/c/77338 to watch this interview with Dr. Gradishar.

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VOL. 3 • NO. 1 • 2019