Harold Burstein, MD, PhD, and Erica Mayer, MD, MPH discuss results from the TRAK-ER trial, which were presented at the 2026 ESMO Breast Cancer Congress.
Doctor Harold Burstein, we're discussing updates from the ESMO Breast Cancer symposium in May 2026 in Berlin, and we're speaking today with Doctor Erica Meyer, one of our senior investigators here at the Dana-Farber and a breast cancer specialist. Erica, bring us up to speed on the Track ER trial and what was new in this study. I know you were the discussant for this work and uh it's certainly an exciting technology. Yeah. So ER is, uh, a really interesting study in the early stage breast cancer setting that is looking at the application of CT DNA testing, looking for, um, MRD status and learning what is the prevalence of this and also what do we do about it. Um, ER is one of the very large studies looking at this in an ER positive population. The study has two parts. There is a surveillance step, and there is a treatment step. What was presented at ESO breast was the surveillance, in which, um, about 1000 patients were enrolled who had hormone receptor positive disease. They've been on their adjuvant endocrine therapy at least 6 months up to 7 years after, uh, initiation, and they entered testing to have a tumor informed CT DNA assay done every 3 months, um, looking for detection positivity. If the test returned positive, then the patient was staged, and if they had no evidence of, Advanced disease on staging, then they would go on to the treatment phase of the study, uh, in which patients were randomized to switch their therapy to a different endocrine based option, uh, fulvestri and palbociclib, or stay on their current regimen. So, again, what was reported was the data from the surveillance phase. Um, the primary endpoint of that data was CT DNA detection rates. What was shown was of the about 1000 patients enrolled, first of all, um, over 80% had successful assay creation. And in that population of patients, about 12% were found to be CTDNA positive. And that number is very much in line with other surveillance studies, both retrospective and prospective. Um, now, importantly, the highest rate of detection was seen at the time of the first test. And for those patients who were cTDNA positive, about 40% had concurrent, um, evidence of disease recurrence, um, a fairly high number, and that actually is in line with other studies. When looking over time at the, of detection, the rate of positivity was fairly consistent between year 1 to year 7 after surgery, and I think you and I have talked about how this data really reflects our understanding of the recurrence biology of hormone receptor positive breast cancer, that there is this persistent risk over time that can extend over many years. Um, patients who, um, were detected, uh, tended to have a higher disease burden at baseline, and that, um, figure about how many patients had, uh, clinical recurrence at the time of detection was actually highest in people who tested positive on the first test. It was almost 70% of patients. So, you know, very interesting data that is actually very aligned with other studies in this setting, both the rate of CTDNA positivity, as well as the rate of, uh, disease recurrence at time of testing. What we're waiting for, though, is the treatment part of the study to see if implementing, uh, an intervention makes this test actually clinically useful and predictive as opposed to just being, uh, uh, essentially refining our prognosis for the patient. So, um, One of the interesting things about this trial, a very high risk group really. I mean, you said 4 more positive nodes, 1 to 3 nodes with a lot of adverse features, and a recurrence rate molecularly of 5 or 6% per year, vastly in excess of populations like Taylor X or Rx ponder, and yet we still only saw an 11%, you know, conversion rate, which do you think that ER positive breast cancer is the breast cancer space where we really want to Look most for these kinds of MRD or CT DNA assays. It's a really interesting question, especially when we contrast this with what's been done in the triple negative space, where obviously this is much higher risk disease. There's actually a track TN study that's a parallel study to this. What is quite consistent in the triple negative cTDNA studies is that that rate of concurrent metastatic disease at time of cTDNA detection. very high. It's almost always at least 70%. The problem with that is what we're trying to find is the window when you can detect the positivity, implement an effective intervention, and then change the outcome, whether that's clearing the CTDNA, whether that's preventing recurrence, whether that's improved in overall survival. We're not really sure what the right end point is, but we need that lead time to allow the intervention and for triple negative if. So many people have that tight connection between CTDNA positivity and they've already recurred. It doesn't give us a window to do that. So we need to figure out how to be more sensitive with our testing and really pick up on the earliest smoke signals of this so it will give us some time to do something for people before they convert to metastatic disease. Well, essentially what you're describing is moving from clinical validity of the test, like we believe the test to clinical utility and obviously still waiting for that data. So when you think about a patient, because we do see these folks in clinic, they come in, they have a positive signaera test or some other assay, what are you doing to evaluate those patients at that moment? Yeah, it's, it's, it's tricky, and this is a problem that all of us in medical oncology are facing because these tests are commercially available and they're marketed to our patients and our patients are having them done. I mean, I think clinically when we have this test, we, we need to scan the patient and assess do they have metastatic disease. But we don't know is there value in continuing to do this test, or should we do something different with their systemic therapy. That's the utility part that we just don't know. Thankfully, there are many studies going on right now, both, um, screening patients and providing an intervention or taking patients with a positive MRD test and then giving an intervention, including trials that we have open and, Open at Dana-Farber. So, we, we are hoping that we can now catch up with the science and do the work that will allow us to make this test useful rather than having it be a valid test, but a test that could create risk for our patients. Well, it sounds like we have to go back to ESMO next year to get the answer to more of these questions. Right. I'm Hal Burstein. I've been with Erica Mayer talking about some of the excitement over molecular testing and trying to think through the endpoints for where it's going to fit most in our clinical practice. Thanks for joining us. Thanks, Hal.
