Applications of ctDNA Assessment in Early Breast Cancer

Barry Rosen, MD, provides an overview of circulating tumor DNA’s role in early stage breast cancer detection and management.


Barry Rosen, MD: As a surgeon, my familiarity with measuring circulating tumor DNA [ctDNA] for my patients with breast cancer really comes up in 2 different settings, one is in the neoadjuvant setting, and the other is in the adjuvant setting. The first test is done prior to initiating treatment. A patient is referred to me who I believe is a good candidate for checking their ctDNA levels. I’ll order that along with the tissue testing to be done prior to initiating treatment, and then once we initiate treatment, whether that’s chemotherapy or surgery, we’ll repeat the testing during treatment and after each landmark in their treatment.

As a breast cancer surgeon, I look at my role as 3-fold. Of course, it’s to do the surgery, but beyond that, I’m also helping navigate the patient through the decisions that they need to make about treatment, and then lastly, I’m responsible for overseeing surveillance. When it comes to surveillance after breast cancer surgery, for local surveillance, we have wonderful testing that’s available, whether through mammography or other supplemental imaging, such as ultrasound or MRI [magnetic resonance imaging]. But when it comes to systemic surveillance for breast cancer, what do we have? Essentially, we have nothing. We have found that doing routine radiologic testing, such as PET [positron emission tomography] scans or CT [computed tomography] scans, really provides no additional value to patients for systemic surveillance compared with just asking them how they’re feeling. Thus, I think what was so intriguing to me when learning about circulating tumor DNA as a method of surveillance, is that you really have to compare it to what our current standard is. When you do that, while we are definitely in the relative infancy of what we need to know and understand about ctDNA breast cancer surveillance, if you compare it to what we have, it’s the best test that we have available. I actually feel an obligation to offer this to all of my patients with breast cancer who have stage II or III disease, or who have a more aggressive form of breast cancer, where the risk of systemic disease is higher.

I’ve been doing this for over 25 years, and patients do very well. It’s been very exciting to be part of breast cancer treatment over the past quarter century; we have made some great strides. But at the end of the day, 20% to 30% of my patients with breast cancer are going to die with metastatic disease. I think that we recognize very well that a subset of our patients is going to present with systemic disease. How do we know that? Well, typically, we will learn that by finding through their traditional staging, for example, that they are node positive, and if they’re node positive, we assume that there is on a microscopic level evidence of systemic disease. We know that a subset of those patients who present with microscopic systemic disease will be cured of their breast cancer by systemic treatment.

Now, when we think of metastatic disease, we don’t think of cure, we think of remission at best. Thus, there must be some point in a patient’s systemic disease when it goes from being curable to being incurable. What we recognize is that our traditional surveillance is typically not going to identify those patients at that tipping point, when intervening could potentially have the most significant impact. My hope is through minimal residual disease, or molecular residual disease testing, we can find that tipping point much sooner. Maybe by intervening at a much earlier stage than when they developed symptoms, we can offer the potential for cure.

Transcript edited for clarity.

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