We were really excited about NSABP B-59/GeparDouze substudy. To give some background information on MRD detection, at a very high level molecular residual disease, or what’s called MRD, refers to tiny amounts of cancer DNA that remains in the body after treatment. But this cancer DNA is not detectable by imaging or standard clinical tools so we’re typically measuring MRD by circulating tumour DNA, or what we call ctDNA, which are small fragments of tumour DNA found in the blood.

So the reason this is important is twofold. One, it can inform patients if they’re higher risk of cancer coming back, and, two, if the cancer does come back we can detect it with molecular residual disease months or years beforehand. So this is the background to the B59/GeparDouze substudy.

What is the clinical need for better predictors of response and recurrence in early triple-negative breast cancer?

What this means for patients is that in practice MRD gives us much more precise information and personalised information to talk to patients. So instead of relying just on clinical and pathological features we can incorporate a dynamic biological marker that reflects what’s actually happening in the body during treatment or after treatment with the patient.

So for patients who are MRD positive it can open the door for discussions about additional therapy, clinical trials, which are very important, or more intensive surveillance. For those patients who are MRD negative it can provide reassurance and potentially avoid over-treatment. So ultimately, as we continue to do more clinical trials, this will help with the conversation related to more individualised care.

What was the study design?

B59/Geparouze, the main study was evaluating neoadjuvant chemotherapy with atezolizumab before surgery but then also after surgery atezolizumab was continued in the patients receiving the atezolizumab. So with this substudy we looked at serial ctDNA and I’m going to give some context to some information that was reported at San Antonio for the B59 substudy which helps us with what was presented at AACR with this substudy.

What stood out most with the B59 substudy from San Antonio was how strongly ctDNA status after surgery correlated with distant recurrence or the breast cancer coming back somewhere else in the body. So, importantly, this was observed in the triple-negative breast cancer population where treatment after surgery is incredibly important and can be challenging in terms of decision making. So in B59 patients who were ctDNA positive after surgery had a higher risk of recurrence, distant recurrence, compared to patients who were ctDNA negative. So post-surgery if patients were ctDNA positive this was associated with a higher risk of recurrence, approximately 30-fold, for distant recurrence compared to those patients who were ctDNA negative.

Secondly, approximately 95% of patients who were ctDNA negative after surgery remained free of distant recurrence at three years. So post-surgery our study helped to determine how patients were going to do, whether they were ctDNA positive or ctDNA negative.

So then with AACR what we presented is that MRD testing, again very meaningful for patients with triple negative breast cancer, so what we did here is we evaluated the ctDNA after neoadjuvant chemotherapy, so after treatment but prior to surgery. The ctDNA detected before surgery was also strongly associated with outcomes but also it was associated with residual disease at the time of surgery. So patients who had detectable ctDNA after completing their neoadjuvant therapy, so this is neoadjuvant chemotherapy with or without atezolizumab, the test predicted lack of a pathological complete response with an 86% positive predictive value. So the ctDNA status prior to surgery was strongly associated with distant recurrence and patients who were ctDNA positive had a higher risk of recurrence.

How might these findings change post-neoadjuvant treatment decision-making in TNBC?

So MRD testing is going to become foundational in terms of a tool used for precision oncology. So we’re moving towards a future where treatment decisions aren’t just based on tumour characteristics, either at baseline or at the time of surgery but evaluating real-time monitoring and evaluating the disease biology. So MRD, as we continue to do clinical trials, will help us guide either escalation of treatment for patients who are high risk for distant recurrence, or potentially de-escalation for patients who are lower risk. So this is a major goal for breast cancer care, is this more individualised care.

So as the evidence continues to grow, MRD really has the potential to reshape how we think about distant recurrence as well as surveillance and long-term disease management and can complement our standard of care procedures in triple negative breast cancer.

Is there anything else you would like to add?

I just think this is a really exciting time in breast cancer as we move in this era of precision oncology with MRD and ctDNA so thank you for having me.