August 29, 2013 at 6:18 PM

Amy Casher: Welcome to Symphony Sisterhood Breast Cancer Dialogues. I am Amy Casher.  Today we are talking with Dr. James Pellicane, Director of Breast Oncology at the Bon Secours Cancer Institute in Richmond, Virginia, about genomic testing for breast cancer.  Specifically, we’ll be probing the issue of how genomic testing stratifies patients into different risk recurrence groups, helping breast cancer patients and their doctors make critical treatment decisions, and also about how intermediate results on first generation genomic test Oncotype DX can complicate matters for many patients and their doctors.  We’ll also be speaking with a recent breast cancer patient, Cari Grundman, for her personal experience with genomic testing and dealing with intermediate results on the first generation genomic test.

Welcome, Dr. Pellicane and Cari.

Cari Grundman: Hi.

James Pellicane: Hey.

Amy Casher: Dr. Pellicane, can you please define genomic testing for us and describe how it helps patients and their doctors target breast cancer treatment more effectively?

James Pellicane: Sure.  Genomic testing really is a look at the molecular function of a breast cancer, or any cancers for that matter, but essentially what it does is it differentiates how a breast cancer looks under the microscope with how it’s going to act within a patient, and it gives us a risk assessment on what the likelihood of that breast cancer coming back somewhere else other than the breast is.  So for instance, breast cancer commonly returns in the bone or in the liver and what genomic testing does is it gives us an idea of what the likelihood of that happening is.

Amy Casher: Can you explain how the two different genomic tests available differ in the way that they stratify patients into different recurrence risk groups?

James Pellicane: Well, the first generation test which you mentioned, the Oncotype DX, was a great first generation test.  It really helped us understand a little bit about genomics, but what it does is it stratifies patients into three risk groups, either low, intermediate or high.  For patients that have a low risk Oncotype score, those patients have a low likelihood of recurrence and therefore don’t need chemotherapy.  For patients with a high recurrence score, those patients can have a higher risk of recurrence and will do well with chemotherapy.  The problem is about 40% of patients will fall into the intermediate risk group, at which point there really is no data to support which way to go one way or the other, and so for 40% of patients, it’s as if they didn’t get the test and we’re relying on old parameters to help us determine whether they should have chemotherapy or not, and we know that those parameters – not that they’re inadequate; they’re just not as good as genomic profiling.  The second generation test, MammaPrint which is from a company called Agendia, basically stratifies patients into one of two risk groups, either high risk or low risk.  There is no intermediate group and that’s really one of the main differences in those two tests.

Amy Casher: What do you see as the main issues with the way in which the first generation genomic test categorizes patients’ recurrence risks, and how does the second generation test resolve these issues?

James Pellicane: Well, again, a couple of the big problems with the first generation test is again the 35% or 40% of patients that are intermediate which you really don’t know what to do with those.  The other problem with the test is that it’s only useful on treated patients, so in other words, patients that get an Oncotype score only attain that score if they’ve been treated with tamoxifen for five years.  So for patients that can’t tolerate the tamoxifen or don’t want to take it for whatever reason, you don’t really have a way of knowing what their recurrence rate is because the test isn’t validated in patients who don’t take tamoxifen.  So those are two very big issues with Oncotype.  With MammaPrint, MammaPrint was developed in a completely different way.  Oncotype was developed by looking at what genes are available and what genes are known at the time of its development and then picking 16 genes that performed well in the assay.  MammaPrint on the other hand basically looked at all 25,000 genes of patients and stratified those genes in order of importance with regards to who recurred with breast cancer and who didn’t recur.  So MammaPrint really let the breast cancer decide which genes were important and which genes weren’t important and it came up with 70 genes which we know now are important.  In fact, 13 of those genes we really don’t know what they do.  We just know they’re important, and it’s in untreated patients, so it’s more pure, it’s more sophisticated and it really covers – when you look at the way breast cancers metastasize or the way they spread, they’re probably about seven different pathways through which they can spread.  Oncotype only looks at three of those pathways whereas MammaPrint looks at all seven, and in my opinion, it’s why there’s no intermediate group.  It’s a much more sophisticated test, it covers all the different pathways, and so it’s better able to split patients into high risk or low risk of recurrence.

Amy Casher: So perhaps because there’s such a large percentage, about 40% as you said, of patients receiving intermediate results on the first generation genomic test, we see very frequent posts on BreastCancer.Org and other breast cancer message boards from patients with the intermediate results who just don’t know what to do about their treatment, and especially whether or not to undergo chemotherapy.  How do you counsel patients who fall into the intermediate category on the first generation test and how can these patients confidently choose whether or not to have chemotherapy?

James Pellicane: Well, for my patients, it’s easy because I don’t use Oncotype anymore, but for patients that come to see me with a second opinion and have an intermediate Oncotype score, I tell them exactly what I said early on in our discussion.  You can’t rely on an intermediate Oncotype score.  If you have it, you have to either have another test or you have to go back to the original parameters that you used to look at before the genomic tests were available which we know are inaccurate.  I mean they’re not inaccurate.  They’re helpful, but they’re not as precise and not as robust as a genomic test, so I basically counsel them and tell them they need to have a MammaPrint run.  So any patient with an intermediate Oncotype score that comes to see me gets a MammaPrint so I can differentiate them into either high risk or low risk group.

Amy Casher: Cari, from what I understand, you had both the Oncotype DX test and the MammaPrint test which is a part of the Symphony breast cancer genomic profile.

Cari Grundman: Yes, I did.

Amy Casher: Can you describe your experience being diagnosed with breast cancer and then in dealing with your genomic test results with both the first generation and second generation tests?

Cari Grundman: Yes.  Last year I had my yearly mammogram and because I have dense breast tissue, I was asked to come back.  I didn’t really think too much about it, but after that appointment, it was recommended that I go and see a breast surgeon, and after doing the biopsy, was diagnosed with stage I breast cancer with two small tumors.  Due to my outlook – I’m very optimistic and whatnot – I opted for a unilateral mastectomy as opposed to getting the bilateral mastectomy and ended up having the surgery two weeks later because we were taking my daughter to college, my husband and I had just launched a new website called “What Do You Pay?” And I wanted to move on.  So two weeks later when I had my surgery and they declared me cancer free, I thought, “Great, I was done” and had completely forgotten that there was another element to this called the Oncotype test which they called me up and said that I had results in the range of 21 which was in the moderate area.  I really didn’t understand what that meant, but because that range, I fell in the low part of the intermediate range, I figured that I was probably fine and after talking with my doctor and whatnot, it was recommended that maybe I want to look into doing the MammaPrint test because there would be a definitive answer whether I was high risk or low risk.  So that’s what we ended up doing, going through the MammaPrint test and despite the fact that I was 21 and seemingly probably fine, it came back that I was high risk.

Amy Casher: How did your results from MammaPrint affect your own treatment decision and your life in general?

Cari Grundman: If anything, I think I was relieved because I talked to a number of different doctors when I had that first result from the Oncotype DX test and was really led down several different pathways in terms of what kind of treatment I should do.  Once this came back as a definitive yes, it took that decision out of my hands because as I had said before, being very optimistic, I figured, “Oh, I’ll be fine.  I don’t have to go ahead and do the chemo,” but I’m so glad to know that I was high risk and that I would benefit from the chemotherapy and have gone through it and come out on the other side, and now I will never have to look back and think, “Oh my gosh, should I have done something more invasive, more extreme, what have you?  Should I have gone for the chemotherapy?” because that choice was made for me.

Amy Casher: So glad that you’re through it, Cari.

Cari Grundman: I am too.

Amy Casher: Dr. Pellicane, if a patient receives an intermediate result on the first generation genomic test and their doctor does not offer the second generation test like Cari’s doctor did, what would you recommend that they do?

James Pellicane: Well, they need to get a second opinion and they need to find someone that will run the MammaPrint to get them a definitive result.  Her case story is not uncommon and physicians want to make the right decision and we tend to be set our ways, but our goal really is to treat patients the best way we know how.  The problem is we’re intuitive creatures, and so when we look at a continuous variable test like Oncotype, we just assume the variable stage continues.  In other words, as the recurrence score goes up, the risk goes up and that’s just not how Oncotype works.  So we intuitively look at those intermediate patients and we say, “Well, you’re in the low part of the intermediate group, so you probably don’t need chemotherapy,” or vice-versa, “You’re in the high part of the intermediate group, so intuitively, you probably do need chemotherapy.”  Unfortunately, if that were the case, there’d be two groups of Oncotype, and there just isn’t. And what we’re finding when we’re running these MammaPrint tests on intermediate Oncotype patients, we’re finding about a 50:50 split in those patients where about half of them are low risk and half of them are high risk.  The problem is they’re spread equally over the whole intermediate subgroup, so in other words, if you come back as a 19 recurrence score which is as low an intermediate score as you can get, you are just as likely to have a high risk MammaPrint as you are a low risk MammaPrint, and so there is no way to tell the difference based on where you fall in the intermediate group, so you cannot take solace that you’re a low intermediate risk patient.  It just doesn’t work that way.  You need a test that’s definitive.  Oncotype is not sophisticated enough to differentiate those intermediate patients whereas MammaPrint is.

Amy Casher: Well, we are so grateful for your thoughts on handling intermediate results on the first generation genomic test.  It’s such a common issue and I know that your clinical wisdom, Dr. Pellicane, and your own personal experience, Cari, will help countless breast cancer patients make more informed decisions about the appropriate breast cancer treatment for them based on a definitive risk recurrence score.  So thank you so much for your time and that…

Cari Grundman: Oh, you’re welcome.

Amy Casher: Thank you.

James Pellicane: Thank you.

Amy Casher: That concludes our dialogue for today.  Thank you so much.