Molecular Changes Provide New Way to Measure Breast Cancer Progression: Adam Brufsky, MD, PhD

Molecular changes such as ESR1 mutations may be more predictive of clinically meaningful, symptom-related progression in patients with breast cancer than waiting for radiographic changes, Adam Brufsky, MD, PhD, of the University of Pittsburgh School of Medicine, concludes based on findings from the phase 3 SERENA-6 trial (NCT04964934) and a follow-up analysis he presented last month at the San Antonio Breast Cancer Symposium.

Watch part 1 to learn more about these findings.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

What do these results demonstrate about camizestrant plus a CDK4/6 inhibitor as a new treatment strategy?

It's consistent with the idea that it is a very safe and potentially effective alternative to aromatase inhibitors [AIs] and CDK4/6 inhibitors in patients with progressive ER [estrogen receptor]-positive metastatic breast cancer who have an ESR1 mutation.

What questions surrounding this treatment regimen remain to be addressed?

I think the big one is—and I think one that people are still thinking about—can you simply continue the AI and then give camizestrant at progression, at actual clinical progression? Why do we really need to do it at ESR1 change in somebody? That's really the big mystery because it really wasn't a crossover study; it didn't cross over when you progressed on an aromatase inhibitor in this study.

To counter that, I'll argue that what we're really doing is affecting what matters to the patients the most, which is their symptoms. I mean, obviously, people want to not progress; they want to live longer, which happens. But what's more important is what's important to the patient.

The patient who went on this trial was really starting to have symptoms to begin with. It was a median of about 20 months, and so I think that's really the important thing people don't talk about too much in SERENA-6. What's happening is that about half of the patients who had an ESR1 mutation did not have any change in their scans, yet they continued to have symptomatic progression. The ESR1 mutation allowed us to intervene with an oral SERD [selective estrogen receptor degrader], which was better than the AI in the setting and actually prevented the deterioration of their quality of life.

The take-home message here is that it may be that molecular changes are more predictive of the progression that's important to the patient, as opposed to waiting for the typical kind of radiology. I think this may be just the tip, the beginning, at least in breast cancer, of an entirely new way of us measuring progression in women with metastatic disease. It may be that we're going to look for minimal residual disease, and we're going to look for changes in things like ESR1 as opposed to simply relying on scans. I think that's really important, especially in breast cancer, where the majority of the disease is in the bone, and it's very difficult in bone to really determine whether someone has a progression or not.