Aditya Bardia, MD, MPH, and Barry Rosen, MD, discuss the role of circulating tumor DNA in the adjuvant setting of breast cancer.
Barry Rosen, MD:Surgery has traditionally been the primary treatment for breast cancer, and other than the exceptional situations for the patient who presents with metastatic disease, surgery is usually the first line of therapy. Whether we do it in a neoadjuvant setting or an adjuvant setting, we know that there’s a subset of patients that will relapse despite surgical treatment, whether supplemented with radiation therapy and/or systemic treatment, whether chemotherapy and/or endocrine therapy. The value of doing ctDNA [circulating tumor DNA] testing is that we may have the opportunity to identify that relapse maybe 12 to 18 months earlier, than through traditional systemic surveillance. If we find those patients earlier, then the goal is that by finding this earlier, we can perhaps identify better ways to treat them, and maybe improve their survival.
Now, there’s also a subset of patients who after chemotherapy and surgery, whether the surgery precedes the chemotherapy, or whether the chemotherapy precedes the surgery, after they’ve completed standard treatment, what we’ve learned from ctDNA testing is that there is a subset of patients who don’t get to zero after completion of their treatment, who have molecular residual disease, MRD. What we’re learning, unfortunately, is patients who don’t get to zero after traditional therapy, their risk of relapse approaches 100%, so we know that if we have patients who we can’t get to zero, we need to find an alternative way of treatment. And one of the wonderful things about systemic treatment now is there’s really a laundry list of different agents that are potentially available. And if we try standard therapy, and we can’t get to zero, I think that’s the exact circumstance where we want to know that by intervening with alternative regimens, that we might ultimately have a better impact on those patients, because without changing it, we know they’re not going to do well.
Aditya Bardia, MD, MPH: At the San Antonio Breast Cancer Symposium, we saw another ctDNA study by Nick Turner, [MD, PhD,] and his team. They looked at patients in the adjuvant setting, who had plasma that was analyzed for ctDNA based on the Signatera assay. As a reminder, the Signatera assay first profiles the tumor to identify tumor-specific mutations, and then detect those in the plasma. It’s like a personalized test. The team found that patients who had detectable ctDNA after surgery, there were 14 out of 48 patients. Those were the ones who were at higher risk of relapse, compared to those who did not have ctDNA detected, with a hazard ratio of 3.7. Thus, it provides proof of principle that detection of ctDNA in the post-surgical time point is associated with worse metastasis-free survival. And in this setting, an intervention that could clear ctDNA might be able to prevent or delay metastases. It’s not ready for prime time yet, but is something that is being investigated in clinical trials, to see if you can A, detect ctDNA, and B, intervene in patients who have detectable ctDNA, in order to improve outcomes.
Transcript edited for clarity.