What is next-generation sequencing and how does it work in guiding breast cancer treatment?
During a recent webinar that we hosted with Dr. Sara Hurvitz of Fred Hutch Cancer Center, we explored the topic of next-generation sequencing, or NGS. Read on to learn more about this type of breast cancer testing and why it matters for patients navigating metastatic breast cancer (mBC).
Q: What is next-generation sequencing, or NGS? How does it work and how can it help identify the best treatment options for patients living with metastatic breast cancer (mBC)?
A: Next-generation sequencing is genomic testing of your tumor sample, or a blood test to look for circulating tumor DNA to see what’s going on in the cancer cells that might be targeted by targeted therapy. So for metastatic breast cancer, it depends on the subtype. If [your breast cancer is] hormone receptor-positive, you don’t necessarily need this testing immediately.
But I think most of us are starting to do it right from the diagnosis. So, most likely your oncologist will send the tumor sample [out] after they get estrogen receptor (ER)/ progesterone receptor (PR) and HER2 testing done on the sample. It’ll be sent out, and then we’ll look at the genetics and those genetic results. If there is an ESR1 mutation that would mean that there is a therapy for it. If there’s a PIK3CA mutation, or another mutation, those mutations tell you how to best treat it, and it also may highlight clinical trial eligibility.
Q: What’s the difference between Guardant 360 and Foundation One Liquid CDx?
A: This is the tip of the iceberg. There are so many companies that have these tests. Some of them require that you submit a blood sample and a tumor sample. Some only work with the tumor sample itself. In addition to Guardant and Foundation, there’s Tempus and Natera. There are all these tests,and they’re all pretty much going after the same information. There are very nuanced differences between them that, I think, is outside the scope of our discussion today. But they’re all looking for mutations that are actionable. So all of them are testing for things that are relevant to making good treatment decisions. But they’re really only relevant for late-stage, metastatic disease. We don’t need to do these assays at this point, for early-stage, curable breast cancer. They’re something to discuss with your oncologist.
Q: Is a liquid biopsy and a minimum residual disease (MRD) test the same?
A: A liquid biopsy is any time you take a blood sample searching for cell-free DNA or circulating tumor DNA. That’s a liquid biopsy because you’re trying to get information about the tumor without doing a needle biopsy, or a surgical biopsy of the tumor in the breast, or wherever it is in the body. A fairly high proportion of patients with metastatic breast cancer will have tumor DNA released from their tumor into the bloodstream, and so you can take a sample of blood and test for the tumor DNA. And that’s a liquid biopsy.
Now, the minimal residual disease, which I think started actually as measurable residual disease, means that you can detect circulating tumor DNA in a patient who has no evidence of a recurrence. So somebody who has had stage I or II or III breast cancer and has been treated, and they have no evidence of disease based on imaging or based on their symptoms. It looks like they’re cured. And you do a blood test, and you detect that there’s actually circulating tumor DNA in the blood. Natera is the biggest marketer of this particular assay.
And the thing about the FDA approval of tests like this is you don’t need to prove that the information will improve patient outcomes. You just need to prove that the test does what it says it will do to be approved. This test has not been proven to help patients, and it’s causing a lot of anxiety and stress and questions when it’s being ordered routinely. And I think–because I see a lot of second opinions of patients–I think what’s happening is the patients are coming to their doctors after they’ve been treated for their triple-negative disease, and saying, “How do I know if my cancer is gone? I heard about Natera? Can you check me for MRD?”
And the doctor does it, and then it comes back positive, and then the doctor and patient don’t know what to do, because there’s no evidence of cancer anywhere in the body. We know from studies that patients who have MRD detectable have a high risk that their next scan, or in the next six months their cancer will be back as metastatic disease. But how is that helpful? How does that make us treat patients more?
Should we start treatment earlier? Is there something we can do to turn them back to a potential cure? Or is it just their fate that metastatic disease has already established, and there is nothing we can do? So this test, in my opinion, belongs in the research realm. We should be conducting a lot of studies, and there are studies ongoing to see if we can act on that information and do something differently. Can we then sort of “rescue” the patient and give them the opportunity for cure? So this really should be done in the research setting, because doing it in the clinical setting, none of us really know what to do with the data. So then we start scanning the patients and doing all these interventions, not knowing if it’s really helping the patient in the end.
Have questions about NGS? Reach out to one of our oncology nurse practitioners using the Ask Outcomes4Me feature in our app.
