Breast Cancer Update for Surgeons, Issue 1, 2017 (Video Program)Case discussion: A 58-year-old woman with T1cN1, ER-positive, HER2-negative BC and a 21-gene assay Recurrence Score (RS) of 12
5:56 minutes.
TRANSCRIPTION:
DR GRADISHAR: This is a woman who is 58, who presented with a T1cN1 disease. So she had a tumor somewhat bigger than a centimeter. I think it was a centimeter and a half. She had a single node that wasn’t grossly involved but met the threshold for being N1 disease. And she was otherwise healthy, had no comorbidities. The molecular analysis of the tumor demonstrated that she was ER-positive, HER2-negative. And the decision of course is, in this woman with Stage II disease, do we feel obligated that we must give her chemotherapy, or could she get away with antihormone therapy alone? And as a baseline, we know this kind of patient will get antihormone therapy. And she’ll get it for at least 5 years. And the decision about longer durations, we’ll face that 5 years into therapy when we come to that bridge. But the initial issue is whether she’d benefit from chemotherapy. And I think with that, this would be a candidate that could either receive a molecular assay, say the MammaPrint®. There’s data with Recurrence Score. There’s data with other platforms, including PAM50. And all of them are prognostic in terms of trying to determine the risk of recurrence. At the present time, the predictive value in terms of determining who’s going to gain benefit from chemotherapy is a little less clear. Obviously, in the case of the Recurrence Score, we have a lot of data in node-negative disease, less in node-positive disease. We have trials that are still not yet complete or reported. MammaPrint had a paper in The New England Journal of Medicine, which I think again confirmed its ability to prognosticate. I would say that that’s probably one of the more confusing papers I’ve ever read, only trumped by the presentation. But I think it is Level 1 evidence. And I think it is a consideration that you could use that as a tool, at least to define the prognosis of this kind of patient. And the reason I bring that up is because, if the prognosis is so good you have to ask the question, how much better could you make it with chemotherapy? So if somebody has an itty-bitty, tiny risk of recurrence with a single node — say they have a couple of percentage points of improving a risk of recurrence — how much better can you make that with chemotherapy? And I think that’s always the question, because you know there’s a finite risk of side effects related to chemotherapy that are often in the range of a couple of percentage points. So in some cases, the prognostic information can be useful even if it’s not predictive. DR LOVE: I think just to qualify for our surgical audience, when you talk about a couple of percentage points, you’re talking about, like, lethal events like cardiomyopathy/acute leukemia. DR GRADISHAR: Correct. So there’s obviously a whole list of short-term side effects: blood counts, hair loss, maybe nausea, et cetera, et cetera. That’s not so much what we’re looking at. But when we balance the benefit of chemotherapy, which in certain populations can be as low as a couple of percentage points, meaning you reduce the risk of recurrence or possibly improve survival, it’s often measured in a very modest improvement in outcome. And similarly, when you think about the very catastrophic side effects, whether it’s a leukemia, whether it’s congestive heart failure, et cetera, those are also measured in a couple of percentage points. So when it’s a complete wash or when the potential of side effects is greater, then I think you really have to think carefully about how strongly you’re going to recommend chemotherapy. DR LOVE: So what actually happened with this lady? DR GRADISHAR: We did get a Recurrence Score on this patient. And the reason that we did that is there is some data, an old SWOG study that Kathy Albain published years ago at this point. And although the numbers are small, biologically the test is really behaving similar to what we would expect in node-negative disease in the sense that, in that study, the patients that had a low Recurrence Score were gaining very little from the addition of chemotherapy. And in that trial, the chemotherapy was CAF. And in this case, the one we’re talking about, the Recurrence Score was also quite low. So we felt comfortable in obviously talking to the patient about the limits of what we knew, that the addition of chemotherapy was likely to add very little additional risk reduction. DR LOVE: What actually was the Recurrence Score? DR GRADISHAR: The Recurrence Score in this case was 12. DR LOVE: So because there’s been a kind of debate a little bit about what constitutes low, whether it’s 10, which was, I think, used in the big paper, or higher, more like 19 in the assay itself. How do you approach that? DR GRADISHAR: I think that it’s a continuous variable, number 1. And the cutoffs were I wouldn’t say arbitrary, but they were somewhat arbitrary. And when the test was initially being validated, it was used as up to 18 as low. And then there was an intermediate range, which is the gray area, which is the subject of a large clinical trial. And then there are those that are high. So in somebody that’s really abutting what we would view as the low of the low, the added benefit of chemotherapy, this being a continuous variable is unlikely to be significant. |