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Genomic Testing in Breast Cancer

Panelists:Adam M. Brufsky, MD, University of Pittsburgh; Sara A. Hurvitz, MD, David Geffen School of Medicine; Joyce A. O'Shaugnessy, MD, Baylor Charles A. Sammons Cancer Center; Hope S. Rugo, MD, University of California; Christy A. Russell, MD, University of Southern California
Published: Friday, Feb 05, 2016


Transcript:

Adam M. Brufsky, MD:
So, we’re all aware that MINDACT was supposed to be presented at San Antonio. I think we’re all a little bit disappointed about that. And my understanding, and I’m curious to hear what other people think about that, my understanding of MINDACT was that they just didn’t have enough events.

Hope S. Rugo, MD: They didn’t. I know that’s the case.

Adam M. Brufsky, MD: The patient did too well I guess.

Hope S. Rugo, MD: So now the question is: is it going to be presented at EBCC or ASCO?

Adam M. Brufsky, MD: Yes.

Hope S. Rugo, MD: It must have been decided.

Adam M. Brufsky, MD: It must have been decided. So, the thing is, will that change the way we think about things? I mean a lot of us kind of said, ‘What’s new about this one that got published,’ right? We all kind of took these pages for granted, as you said Christy. But the issue is: does it do anything different for the way we use OncotypeDx?

Christy A. Russell, MD: Well, I think it does because there are still many people throughout this country who will not consider doing the recurrence score on a very young patient or high-grade patients. So what was presented in a poster, actually by Steve Shack, who’s a medical director of Genomic Health, was this very fascinating study of over 40,000 women who had had Oncotype scores and were matched to SEER. They have all the SEER mortality data and whether patients got chemotherapy or not. And they have their Oncotype scores, and they went to a third-party vendor to match the patients.

Adam M. Brufsky, MD: Were they able to do that?

Christy A. Russell, MD: Yes.

Adam M. Brufsky, MD: I thought SEER is anonymized. It’s not anonymized?

Christy A. Russell, MD: Apparently, the National Cancer Institute allowed this to occur. A third party has now matched over 40,000 patients, and the outcomes of this are very, very fascinating. However, what was more interesting to me is that in California, for patients who are lymph node–negative between the ages of 50 and 60 and who have ER-positive cancers, the use of Oncotype is under 50%.

Adam M. Brufsky, MD: Really?

Christy A. Russell, MD: Yes. So across the country, the best state was New Mexico. Who knows why, but it was like 55%. The underuse of Oncotype to me was shocking across this country, and so you don’t know [if] people’s motivations are ordering it or not ordering it. You know maybe in a very old population you would consider not ordering it because you’re not going to give chemotherapy. I’m not sure people are using this.

Hope S. Rugo, MD: I think that there are patients to whom I’m not going to give chemotherapy. So they were grade 1, ER or PR of 100%, 1 centimeter tumor (0.8 or 1.2 cm), and I see Oncotyping sent a lot of times in those patients when I don’t really care if they have a score of 24, you know? I’m not going to give them chemotherapy. So when I saw those data, I agree, it was surprising. But I think that there may be more to it than you can unearth from this particular dataset, which is an interesting question.

Adam M. Brufsky, MD: So we have two issues here then. We have: are we even going to use the existing OncotypeDX, but assume MINDACT comes out. And the way MINDACT is designed, from my understanding of it, is that women are randomized in a group to either have a discordant MammaPrint 70 gene score versus clinical score because clinical is based kind of on Oncotype, on Adjuvant! Online. And if they’re discordant, they’re randomized to no chemo or chemo, endocrine therapy alone or endocrine and chemo.

Hope S. Rugo, MD: They’re randomized to using either MammaPrint results or the clinical pathologic score.

Adam M. Brufsky, MD: Correct.

Hope S. Rugo, MD: So if, for example, you were randomized to MammaPrint and you were low risk, you wouldn’t get chemo. If you were randomized to MammaPrint and you were high risk, you would get chemotherapy regardless of the clinical pathologic data.

Adam M. Brufsky, MD: Right.

Hope S. Rugo, MD: And a third of the patients have node-positive disease or so.

Adam M. Brufsky, MD: And about 10% are HER2-positive from my understanding.

Hope S. Rugo, MD: Yeah, so it’s going to be fascinating.

Adam M. Brufsky, MD: It is. And the idea behind that is if you’re low-risk MammaPrint and you get hormone therapy alone—I think they project you are 5-year DFS [disease-free survival]—you’re like 92%. I think that’s the number they’re shooting for with their statistics. They’re really fascinating. I mean, will you guys change what you do if MINDACT turns out to be positive in that way?

Hope S. Rugo, MD: Positive meaning?

Adam M. Brufsky, MD: Meaning that if you’re a low-risk MammaPrint, either you’re node-positive...

Hope S. Rugo, MD: It doesn’t matter what your cancer is.

Adam M. Brufsky, MD: Doesn’t matter, node-positive. Getting back to what you were saying; 5 centimeter tumor, node-positive, maybe stage T1c, triple-positive (ER-positive, HER-2-positive). Would you switch then to using the Agendia test?

Christy A. Russell, MD: Well, only if it shows a benefit from chemotherapy. I mean, that’s the purpose: they’re being randomized to chemotherapy or no chemotherapy.

Adam M. Brufsky, MD: Right.

Hope S. Rugo, MD: No, you’re treated based, I think, on your score. Right?

Sara A. Hurvitz, MD: You wouldn’t have chemo if you were low risk.

Adam M. Brufsky, MD: If you were low risk, you wouldn’t have chemotherapy. If you’re high risk, you would.

Hope S. Rugo, MD: You’re randomized to either being treated based on MammaPrint or clinical pathologic treatments.

Adam M. Brufsky, MD: And the assumption is that everybody …

Hope S. Rugo, MD: How about you two?

Adam M. Brufsky, MD: I think that’s the point. The devil’s going to be in the details. I agree with you.

Joyce A. O’Shaughnessy, MD: I think it’s a little challenging, yup, yup. But I do think it will help. I mean, I’ve been waiting for that prospective data in a randomized fashion even though the randomization is a bit unconventional. Yes, I think if they really show that if you have a low MammaPrint—even if the Adjuvant! Online is high risk and you’re discordant and you come out that you do very, very well with just endocrine therapy alone—it will be very important food for thought. It’ll be another bulb on the Christmas tree. It’s not going to be just one thing that’s going to change all of practice. It’s just another thing in the big picture.

Christy A. Russell, MD: The concern is the other group to me. What if they have a high MammaPrint score and low clinical score? And that group may actually do well because to me, high MammaPrint score is too inclusive. I think it’s too broad of a prognostic group, from my point of view, because there’s really validated and untreated patients. So it will be interesting to see in patients who get an endocrine therapy because they’re ER-positive and don’t get chemotherapy because of good clinical features. I think that group will be interesting.

Hope S. Rugo, MD: We actually presented; it’s a little poster in San Antonio. We looked at patients in a couple of US oncology groups and then at UCSF who’d had both MammaPrint and Oncotype. And we looked at just the node-negative group. And their tests are not very concordant, which is fascinating. And, of course, the intermediate risk complicates it. But if you use the TAILORx definition, the low risks are really concordant and the high risks are really concordant, and the rest is just a complete mess. So it’s an interesting question. I mean, you have a patient who has a 14-cm lobular cancer and three positive nodes and has an Oncotype score of 2. What do you do with that patient? Give them hormone therapy and they relapse.

Adam M. Brufsky, MD: But, they may have relapsed anyway.

Hope S. Rugo, MD: Yes, exactly.
                                                                                                                                                                                                                                                                                                             
Transcript Edited for Clarity
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Transcript:

Adam M. Brufsky, MD:
So, we’re all aware that MINDACT was supposed to be presented at San Antonio. I think we’re all a little bit disappointed about that. And my understanding, and I’m curious to hear what other people think about that, my understanding of MINDACT was that they just didn’t have enough events.

Hope S. Rugo, MD: They didn’t. I know that’s the case.

Adam M. Brufsky, MD: The patient did too well I guess.

Hope S. Rugo, MD: So now the question is: is it going to be presented at EBCC or ASCO?

Adam M. Brufsky, MD: Yes.

Hope S. Rugo, MD: It must have been decided.

Adam M. Brufsky, MD: It must have been decided. So, the thing is, will that change the way we think about things? I mean a lot of us kind of said, ‘What’s new about this one that got published,’ right? We all kind of took these pages for granted, as you said Christy. But the issue is: does it do anything different for the way we use OncotypeDx?

Christy A. Russell, MD: Well, I think it does because there are still many people throughout this country who will not consider doing the recurrence score on a very young patient or high-grade patients. So what was presented in a poster, actually by Steve Shack, who’s a medical director of Genomic Health, was this very fascinating study of over 40,000 women who had had Oncotype scores and were matched to SEER. They have all the SEER mortality data and whether patients got chemotherapy or not. And they have their Oncotype scores, and they went to a third-party vendor to match the patients.

Adam M. Brufsky, MD: Were they able to do that?

Christy A. Russell, MD: Yes.

Adam M. Brufsky, MD: I thought SEER is anonymized. It’s not anonymized?

Christy A. Russell, MD: Apparently, the National Cancer Institute allowed this to occur. A third party has now matched over 40,000 patients, and the outcomes of this are very, very fascinating. However, what was more interesting to me is that in California, for patients who are lymph node–negative between the ages of 50 and 60 and who have ER-positive cancers, the use of Oncotype is under 50%.

Adam M. Brufsky, MD: Really?

Christy A. Russell, MD: Yes. So across the country, the best state was New Mexico. Who knows why, but it was like 55%. The underuse of Oncotype to me was shocking across this country, and so you don’t know [if] people’s motivations are ordering it or not ordering it. You know maybe in a very old population you would consider not ordering it because you’re not going to give chemotherapy. I’m not sure people are using this.

Hope S. Rugo, MD: I think that there are patients to whom I’m not going to give chemotherapy. So they were grade 1, ER or PR of 100%, 1 centimeter tumor (0.8 or 1.2 cm), and I see Oncotyping sent a lot of times in those patients when I don’t really care if they have a score of 24, you know? I’m not going to give them chemotherapy. So when I saw those data, I agree, it was surprising. But I think that there may be more to it than you can unearth from this particular dataset, which is an interesting question.

Adam M. Brufsky, MD: So we have two issues here then. We have: are we even going to use the existing OncotypeDX, but assume MINDACT comes out. And the way MINDACT is designed, from my understanding of it, is that women are randomized in a group to either have a discordant MammaPrint 70 gene score versus clinical score because clinical is based kind of on Oncotype, on Adjuvant! Online. And if they’re discordant, they’re randomized to no chemo or chemo, endocrine therapy alone or endocrine and chemo.

Hope S. Rugo, MD: They’re randomized to using either MammaPrint results or the clinical pathologic score.

Adam M. Brufsky, MD: Correct.

Hope S. Rugo, MD: So if, for example, you were randomized to MammaPrint and you were low risk, you wouldn’t get chemo. If you were randomized to MammaPrint and you were high risk, you would get chemotherapy regardless of the clinical pathologic data.

Adam M. Brufsky, MD: Right.

Hope S. Rugo, MD: And a third of the patients have node-positive disease or so.

Adam M. Brufsky, MD: And about 10% are HER2-positive from my understanding.

Hope S. Rugo, MD: Yeah, so it’s going to be fascinating.

Adam M. Brufsky, MD: It is. And the idea behind that is if you’re low-risk MammaPrint and you get hormone therapy alone—I think they project you are 5-year DFS [disease-free survival]—you’re like 92%. I think that’s the number they’re shooting for with their statistics. They’re really fascinating. I mean, will you guys change what you do if MINDACT turns out to be positive in that way?

Hope S. Rugo, MD: Positive meaning?

Adam M. Brufsky, MD: Meaning that if you’re a low-risk MammaPrint, either you’re node-positive...

Hope S. Rugo, MD: It doesn’t matter what your cancer is.

Adam M. Brufsky, MD: Doesn’t matter, node-positive. Getting back to what you were saying; 5 centimeter tumor, node-positive, maybe stage T1c, triple-positive (ER-positive, HER-2-positive). Would you switch then to using the Agendia test?

Christy A. Russell, MD: Well, only if it shows a benefit from chemotherapy. I mean, that’s the purpose: they’re being randomized to chemotherapy or no chemotherapy.

Adam M. Brufsky, MD: Right.

Hope S. Rugo, MD: No, you’re treated based, I think, on your score. Right?

Sara A. Hurvitz, MD: You wouldn’t have chemo if you were low risk.

Adam M. Brufsky, MD: If you were low risk, you wouldn’t have chemotherapy. If you’re high risk, you would.

Hope S. Rugo, MD: You’re randomized to either being treated based on MammaPrint or clinical pathologic treatments.

Adam M. Brufsky, MD: And the assumption is that everybody …

Hope S. Rugo, MD: How about you two?

Adam M. Brufsky, MD: I think that’s the point. The devil’s going to be in the details. I agree with you.

Joyce A. O’Shaughnessy, MD: I think it’s a little challenging, yup, yup. But I do think it will help. I mean, I’ve been waiting for that prospective data in a randomized fashion even though the randomization is a bit unconventional. Yes, I think if they really show that if you have a low MammaPrint—even if the Adjuvant! Online is high risk and you’re discordant and you come out that you do very, very well with just endocrine therapy alone—it will be very important food for thought. It’ll be another bulb on the Christmas tree. It’s not going to be just one thing that’s going to change all of practice. It’s just another thing in the big picture.

Christy A. Russell, MD: The concern is the other group to me. What if they have a high MammaPrint score and low clinical score? And that group may actually do well because to me, high MammaPrint score is too inclusive. I think it’s too broad of a prognostic group, from my point of view, because there’s really validated and untreated patients. So it will be interesting to see in patients who get an endocrine therapy because they’re ER-positive and don’t get chemotherapy because of good clinical features. I think that group will be interesting.

Hope S. Rugo, MD: We actually presented; it’s a little poster in San Antonio. We looked at patients in a couple of US oncology groups and then at UCSF who’d had both MammaPrint and Oncotype. And we looked at just the node-negative group. And their tests are not very concordant, which is fascinating. And, of course, the intermediate risk complicates it. But if you use the TAILORx definition, the low risks are really concordant and the high risks are really concordant, and the rest is just a complete mess. So it’s an interesting question. I mean, you have a patient who has a 14-cm lobular cancer and three positive nodes and has an Oncotype score of 2. What do you do with that patient? Give them hormone therapy and they relapse.

Adam M. Brufsky, MD: But, they may have relapsed anyway.

Hope S. Rugo, MD: Yes, exactly.
                                                                                                                                                                                                                                                                                                             
Transcript Edited for Clarity
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