Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementRoles of next-generation sequencing and liquid biopsy in mBC
5:10 minutes.
TRANSCRIPTION:
DR LOVE: So this one, interesting, this is from Dr Ibrahim, a 64-year-old woman who, in 2013, had an ER-positive, HER2-negative tumor, multiple positive nodes. She was somewhat frail. Gets a Recurrence Score, it’s high, 39, so the patient gets docetaxel/cyclophosphamide. Okay? So then a year later develops hepatic lesions. The biopsy is positive, still ER-positive, HER2-negative. The patient gets exemestane/everolimus. I think she was on an AI at that point and has a complete remission. Okay? Then a year later has new hepatic lesions that are biopsied, and now the biopsy shows that the patient is HER2-positive. And it’s confirmed with next-generation sequencing. And actually, the patient was given capecitabine/trastuzumab and had a complete clinical response. So the question that Dr Ibrahim had was, there were a number, really. First of all is, how often do you rebiopsy a patient? Here’s a patient where rebiopsy really had a very important role. Second of all, where does next-generation sequencing fit in, because that’s kind of where the clue came from in this situation? And finally, what about liquid biopsies instead of tissue biopsies in patients with metastatic disease, again attempting to find clonal evolution? DR SMITH: I think this patient illustrates that it is worth rebiopsying. It’s not common for this to happen, but it does happen. This is by no means unique. And this patient has benefited enormously. So I think if it’s easy to rebiopsy, then the answer is yes. Next-generation sequencing is what every patient nowadays wants. And the story is that we’ll find a mutation and it will be targetable, and we’ll give you the targeted therapy against it. The practical problem is that there aren’t that many effective targeted drugs around just now. Fabrice Andre in Paris ran a large French study which was extremely skillfully done in terms of logistics, in which a large series of patients with metastatic breast cancer had rapid next-generation sequencing. And I can’t remember the details, but a very significant number had identifiable mutations, but only something like 6%, 7% were able to gain from targeted therapy because of it. So it’s where we’re going, but we just need more targeted drugs, and they’ll come along. Liquid biopsies, I think, is, I was going to say, the next big thing. I think it’s the current big thing. I think we’re here. My colleague Nick Turner at the Marsden is one of the pioneers in this. And what we’ve shown and others have shown as well is that you can certainly detect circulating tumor in DNA in the great majority of patients with metastatic disease. And you’re picking up mutations, so you’re detecting them. The mutations correlate with the mutations in the original cancer or, indeed, in the metastasis. So the tumor biopsy correlates with the tumor DNA in the blood. So there’s very potential applications for this. First of all, it’s not so easy to keep doing tumor biopsies. But, of course, it’s very easy indeed to keep doing blood sampling. And the other question, which is looking very exciting, is that we can pick up recurrence a considerable length of time before you can with routine standard measurements, because the tumor DNA appears in the blood or arises in the blood several months before there’s any other evidence of relapse. The question is, is there any advantage to the patient apart from making them very anxious indeed? But assuming that we can start to use these affected targeted therapies — and we’ve got more and more of them — probably it is going to be a big advantage. So I think liquid biopsy is going to revolutionize the way we manage breast cancer. We’re doing this in all patients. And if we can find the targeted treatment, we’re going to be using it in metastatic disease much earlier than before. And hopefully that’s going to improve long-term outcome. |