Genomic Assays: What Are the Different Kinds and How Do They Work?

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Jamie DePolo: Hello. Thanks for listening. Our guest is Brian Wojciechowski, MD, who practices medical oncology in Delaware County, Pennsylvania, at Riddle, Taylor, and Crozer hospitals, and also serves as Breastcancer.org's medical adviser. A native of South Philadelphia, he trained at Temple University School of Medicine and Lankenau Medical Center.

Dr. Wojciechowski is a sought-after speaker on the topics of medical ethics and the biology of cancer.

There are several genomic tests, also called genomic assays, that analyze a sample of a breast cancer tumor to see how active certain genes are. The results of these tests help people and their doctors decide if more treatments after surgery would offer more benefits than risks.

Dr. Wojciechowski joins us to explain the six genomic tests currently used for breast cancer. Dr. Wojo, welcome to the podcast.

Dr. Brian Wojciechowski: Thanks for having me again, Jamie.

Jamie DePolo: So, unless you'd like to do it differently, I thought we'd talk about the tests in alphabetical order. So, the first one is the Breast Cancer Index Test. So, what type of breast cancer is it used for, and what do the results show?

Dr. Brian Wojciechowski: Well, the Breast Cancer Index is just one of these genomic tests, and of course, a genomic test is really testing the genes of the tumor itself. Now, we all have our normal genes, but tumors have genes, as well, a lot of which are mutated or otherwise altered. So, when you're doing a genomic test, you're looking...you're testing the genes of the tumor itself to predict the behavior of the tumor into the future. And that goes for all these tests that we're going to talk about today.

The Breast Cancer Index Test is really for endocrine therapy, not for chemotherapy. It is used to determine if a woman should have more than five years of endocrine therapy. And the way I use the test is, when five years rolls around, if she says to me, “There is no way I will go more than five years, I don't care what you say.” And the typical situation is the woman who knows her stop date, she'll say to me something like, “All right, I'm done on July 18, 2023, right, doc?”

So, you know that she's been counting down the days, and she has no intention of going beyond five years. If that's the case, I don't even do this test, because it's probably not going to change anything. But this test can be done in anyone with hormone receptor-positive breast cancer that is lymph node-negative or with just a few lymph nodes, one to three, and no metastatic disease. And what it does is it predicts the risk of what we call a late recurrence.

That is recurrence after five years, and if the risk is high enough, then we recommend continuing the hormonal therapy out to 10 years, you know, unless there's reasons not to do it. Like, you know, she's having trouble tolerating the medicine or she's developed really bad osteoporosis. But this test is for the woman who is willing to go 10 years, but wants to know more, wants to know if 10 years would really give her any benefit.

Jamie DePolo: Okay, and just to put it all in one sentence, this is for early-stage, hormone receptor-positive breast cancer after five years of endocrine therapy?

Dr. Brian Wojciechowski: Right. And it's important to note that she can be lymph node-positive, one to three lymph nodes, but anything more than that, we generally don't use these kind of tests, because we feel that patients with more than three lymph nodes are just...we just know they're at high risk for recurrence. So, we're going to try to push them more to have chemo or endocrine therapy or even extra endocrine therapy. So, this one is really not indicated if the tumor's greater than 5 centimeters or if there's more than three [positive] lymph nodes.

Jamie DePolo: Okay, and could this be used for a man with breast cancer? I wasn't sure if men are ever advised to take 10 years of hormonal therapy.

Dr. Brian Wojciechowski: There's really not enough men in the studies that develop these tests. I believe I have ordered one or two for men when the decision was up in the air, with the caveat that there's not a lot of data to support that. Can be done. I know that much.

Jamie DePolo: Okay. So, should we move on? The next one on my list is the EndoPredict Test.

Dr. Brian Wojciechowski: Yeah. So, the EndoPredict actually gives you information on the risk of recurrence, both at 10 years and at 15 years, and gives you data on the benefit of chemotherapy and extended endocrine therapy, as well. Again, this is for a similar patient population. This is not for women with metastatic disease, that is distant metastatic disease. It's for women with hormone receptor-positive, HER2-negative, and zero or one to three lymph nodes. This one also gives you some data about the benefit of chemotherapy, not just the benefit of endocrine therapy, and that's one of the other things that differentiates it from the Breast Cancer Index Test.

Jamie DePolo: Okay. So, the Beast Cancer Index Test, you would do it, say, five years...after the woman's had five of hormonal therapy. EndoPredict, it sounds like you do after surgery to decide if chemotherapy would be beneficial?

Dr. Brian Wojciechowski: Yes, you could do that. You could also do it later if you're trying to predict the benefit of endocrine therapy. It's like you're saying if you're trying to predict chemotherapy benefit, it only really makes sense to do it after surgery, because chemo needs to be done right away if it's needed.

Jamie DePolo: Okay. So, this one could be done right after surgery, or it could be done after five years of hormonal therapy?

Dr. Brian Wojciechowski: That is correct.

Jamie DePolo: Okay. So, we'll move onto MammaPrint.

Dr. Brian Wojciechowski: So, MammaPrint gives you a low or a high-risk category. There's two answers, low or high, and it's used to predict the...to give you prognosis at 10 years. And again, similar requirements. Non-metastatic disease, tumor up to 5 centimeters, up to three lymph nodes, all ages. It's for newly diagnosed breast cancer, stages I, II, or III. So, it's not for down the road, and you can actually order it for triple-negative and HER2-positive breast cancers, as well. Although we don't usually use it for that purpose, because women with triple-negative or HER2-positive are almost always a candidate for chemotherapy.

Jamie DePolo: And so, MammaPrint, done right after surgery, looks at...did you say late recurrence? So, it's looking at recurrence at 10 years, or is it looking at recurrence in five years and 10 years? That's what I can't remember.

Dr. Brian Wojciechowski: Well, what they say is 5 to 10 years.

Jamie DePolo: Okay, and it can be done, obviously, as you said, in hormone receptor-positive or hormone receptor-negative disease, which I think sort of sets it apart from some of these other tests that are really aimed at hormone receptor-positive disease?

Dr. Brian Wojciechowski: A hundred percent. Yeah, that...it's very unique that way. MammaPrint is related to a test called BluePrint, made by the same company, that gives...that tests more genes and gives you a different category of cancer. So, you've...you know, we've talked about basal-like. We've talked about HER2 enriched, etc., which is, more or less, used for research these days.

Jamie DePolo: I see. Okay. I didn't put the BluePrint on my list, because I feel...is BluePrint used for breast cancer, or is it really more MammaPrint?

Dr. Brian Wojciechowski: BluePrint is used for breast cancer, but it gives you a different category of looking at the cancer.

Jamie DePolo: Okay. So, it's more, as you said, for the subtype, rather than determining if treatments after surgery would be beneficial?

Dr. Brian Wojciechowski: That's right, and I think it would mostly be used in a research setting.

Jamie DePolo: Okay. So, it's not commonly ordered for somebody who's newly diagnosed?

Dr. Brian Wojciechowski: Right. It tells you if the cancer is luminal A, luminal B, basal-like, HER2-enriched, those sort of categories.

Jamie DePolo: Okay. Anything else about MammaPrint that we should talk about?

Dr. Brian Wojciechowski: No, I don't think so.

Jamie DePolo: Okay. Then we have Oncotype, and there are two Oncotype genomic tests, one for invasive breast cancer and one for DCIS. So, I'm going to ask you to start with the one for invasive cancer.

Dr. Brian Wojciechowski: Yeah. So, the one for invasive cancer, which is called Oncotype DX, is probably the most commonly used tests of all these genomic tests. And it's used after surgery, again, on hormone receptor-positive, HER2-negative patients, with up to three lymph nodes, to determine, A: the risk of recurrence, and B: what is the benefit of having adjuvant chemotherapy. Again, this is not used in the metastatic setting, but it's used to detect...it's used to predict the benefit of chemotherapy.

Jamie DePolo: Okay. Okay, and you get...I know there's been...as you said, there's been probably more research on Oncotype because it's been around the longest. So, there is a whole range of...you get a recurrence score, and then based on your age and your score, that's how the results are interpreted.

Dr. Brian Wojciechowski: If you're over 50 versus under 50, the scores are different.

Jamie DePolo: Okay, and so, as you said, it helps predict recurrence and the benefit of chemotherapy after surgery?

Dr. Brian Wojciechowski: Exactly.

Jamie DePolo: Okay. Then what does the Oncotype DCIS test do?

Dr. Brian Wojciechowski: Yeah. So, DCIS, as our listeners might know, is basically stage 0 breast cancer. So, it's non-invasive. You know, it doesn't spread. It doesn't go metastatic, and the idea with DCIS is to prevent a recurrence in the same breast and prevent a future invasive breast cancer, say, a stage I, II, or III breast cancer. So, Oncotype DCIS is a little different because what it does is it deals with the question of radiation, not the question of hormone therapy. It's supposed to determine if there's a subset of patients who will not benefit from radiation for their DCIS.

Jamie DePolo: Okay, and that's after surgery, as well, correct?

Dr. Brian Wojciechowski: Yeah, that's right.

Jamie DePolo: Okay. Okay. How common is that? Like, do you often use that for patients with DCIS? I guess I'm wondering. I really don't know as far as treatment goes. You know, is it recommended that most people get radiation or now, with this test, is it more like, well, let's do the test and decide?

Dr. Brian Wojciechowski: Yeah. It is recommended that most people get radiation and hormonal therapy with DCIS. So, you can get an Oncotype DCIS, but it often doesn't change management, and I really can't say that it's a standard of care right now. I think I will use it when...you know, when I have a patient who is really on the fence about radiation, not sure what she wants to do, and this might be a way to tip one way or the other.

Jamie DePolo: Okay, and then, finally, the sixth test is the Prosigna Breast Cancer Prognostic Gene Signature Assay, and that also, again, treatments after surgery. So, what can you tell us about that test?

Dr. Brian Wojciechowski: Yeah. So, this one is also known as the PAM50. Used to be called the PAM50, and again, it's for early-stage, hormone receptor-positive breast cancer. It's trying to help us make treatment decisions based on 10-year risk of distant recurrence. So, you know, that's recurrence outside of the breast to, for example, the bones, the liver, the lungs, that sort of thing.

You know, it also is trying to help us determine about hormonal therapy and the duration. So, in other words, 10 years versus five years of hormonal therapy. And I think...I mean, I have not used this test, but I think I would use it the same way I would use Breast Cancer Index on a patient who is motivated to take five more years of treatment, but doesn't want to do it unless she really has to do, unless she's sure there's a benefit.

Jamie DePolo: Okay, and you mentioned distant recurrence. So, if I'm understanding correctly, this is really the only test that offers an estimate of the risk of metastatic disease? In other words, that the cancer's going to come back as a metastatic?

Dr. Brian Wojciechowski: These other tests do give you metastatic prognosis. The Prosigna, I think that's the only one that doesn't give you local recurrence.

Jamie DePolo: Oh, I see.

Dr. Brian Wojciechowski: Or one of the ones that doesn't give you local recurrence.

Jamie DePolo: That's helpful. So, we have these six tests, and I know you talked about when you would use them, but from sort of the patient perspective, going to see their oncologist, you know, should they be asking for a test? Like, how do you decide? It seems like some of them do almost the same thing. So, how do you decide which one to use?

Dr. Brian Wojciechowski: As a doctor, we're going to decide which one to use based on which one has the best evidence behind it and which one is appropriate for our patient in their individual circumstances. So, we're looking at personalized medicine here. And we also want to have a thorough conversation with the patient about, well, if we do this test -- and they're very expensive -- if we're going to spend a few thousand dollars to do this test, is it really going to change our treatment recommendation?

So, for example, if I'm talking to a patient and she's telling me, “Doc, there's just no way I'm going to have chemotherapy no matter what,” then I'm going to suggest that we don't do a genomic test, because the whole purpose of it is to determine whether or not she should get chemotherapy. Now, if she wanted prognosis, you could certainly order a test just to determine what the prognosis is, even if someone is not getting chemotherapy.

But I like to think I'm pretty good at determining prognosis without these tests, especially if we're not going to do chemo, you know, based on the hormone receptor status, the HER2 status, you know, the elements of the pathology report. So, I really try to not do these tests, unless it's going to affect my management or my treatment recommendations, and I try to have that discussion with the patient before I order it.

Jamie DePolo: Okay. Does it ever happen...do patients ever come to you and say, I read about this test. Should I have it? Does that ever happen?

Dr. Brian Wojciechowski: Not to me personally, because I work in a system where there's a really good multidisciplinary breast cancer group. So, the surgeon and the radiation oncologist and the medical oncologist and you know, other sort of allied health partners, and it's just standard to have this discussion. So, it usually comes up before the patient asks. It is important if you're going to have breast...if you have breast cancer, to be at a place like that, that has a good, strong multidisciplinary team.

Jamie DePolo: Okay. Thank you for that. And then, finally, I had read some studies that talk about how the people in the studies that validated all these genomic tests were not very diverse. They were overwhelmingly white and that the results of some of these tests -- I've seen Oncotype DX specifically mentioned -- that they're not as accurate in women who are not white. And so I guess I'm just wondering about your thoughts on that. Do you know, are studies being done to sort of revalidate the tests in more diverse populations? What's your take?

Dr. Brian Wojciechowski: Yeah, I don't know if studies are being done to revalidate the tests in more diverse populations, although I think they should be done. You know, for various reasons, Caucasians are overrepresented in medical research studies and minorities are underrepresented, and that could be for a lot of different reasons, which I won't speculate about right now. But the other thing is that, yeah, I mean, generally speaking, African-American women tend to have more aggressive tumor biology. So, with any of these assays, we might not be getting the whole picture for minority populations.

But there really...there's no evidence that minority populations shouldn't have these tests and shouldn't have the same sort of interpretation based on the biology, because the good thing is that, you know, we're doing very personalized medicine. We're testing for a lot of different genes, and what we hope is that, you know, the biology of the tumor is generalizable across races. So, I would definitely encourage, you know, our patients who are non-Caucasian to, you know, get these tests done and you know, follow the results until we get better and more complete data on different minority sub-populations.

Jamie DePolo: Okay. Have you heard about any, say, new tests being developed? I'm just curious, are more...I don't know if it's aimed at non-white women or non-white people, or is that not going on?

Dr. Brian Wojciechowski: I don't know everything that's going on out there, but...

Jamie DePolo: Brian, you don't? Why not?

Dr. Brian Wojciechowski: I will tell you, it's a challenge because, again, as I said before, minorities are really very underrepresented in clinical trials for various reasons. So, you know, it's hard to say when we're going to get better data and information, but I think for the moment, we really ought to encourage our patients who are non-white to not only enroll in clinical trials, but to have these tests done, because I think they should be valid, because, again, we're looking at biology of the tumor, and this is very personalized, and even Caucasians are not a homogenous group of people. So, you know, I think until we know more, we should just continue to use these for all patients no matter the race.

Jamie DePolo: All right. Well, Dr. Wojciechowski, thank you so much. I appreciate you explaining all this, and thank you again.

Dr. Brian Wojciechowski: All right, Jamie. Thank you.