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Managing Luminal A and Luminal B 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 12, 2016


Transcript:

Adam M. Brufsky, MD:
I know people have been disagreeing with me about this since it came out, but I think one of the most fascinating papers at San Antonio this year was the presentation was by Nielsen.

Joyce A. O’Shaughnessy, MD: Oh.

Adam M. Brufsky, MD: So, who wants to take on that one? Christy, you want to describe the Nielsen paper because that gets to Hope’s question exactly of what to do.

Christy A. Russell, MD: So, the Nielsen paper was looking at whether the luminal A and luminal B, whether they’re actually predictive of benefit from chemotherapy. Because certainly a lot of people in the community say, ‘Well, I have a luminal A patient so they obviously won’t benefit from chemotherapy.’ It’s like, where are those data?

Adam M. Brufsky, MD: We have it.

Christy A. Russell, MD: So now we have a little bit of data.

Adam M. Brufsky, MD: A little bit.

Christy A. Russell, MD: Okay, fine.

Joyce A. O’Shaughnessy, MD: No endocrine therapy though.

Christy A. Russell, MD: When they did their presentation, they recognized that there are very few studies out there that have leftover blocks for which there’s long-term information about the patients, and they went back to a really old trial where patients either got cyclophosphamide/ methotrexate/ fluorouracil (CMF), Cytoxan, placebo, or no therapy at all.

Joyce A. O’Shaughnessy, MD: Levamisole.

Christy A. Russell, MD: Yeah. Levamisole.

Adam M. Brufsky, MD: It’s very, very old. We all are. Sara might be the only one here who’s not.

Christy A. Russell, MD: So they separated the groups. They showed the patients who got CMF and Cytoxan essentially did the same long term from the study and that the other groups didn’t do so well. So what it showed is that the luminal A’s did not seem to benefit from chemotherapy and that the luminal B’s, or everything else, including basal subtype and HER2, did seem to get some benefit from chemotherapy. Endocrine therapy was not used as a standard of care.

Adam M. Brufsky, MD: Because it wasn’t back then.

Christy A. Russell, MD: Right.

Adam M. Brufsky, MD: Back then, no one used endocrine therapy; it wasn’t standard of care 25 years ago.

Christy A. Russell, MD: But do you know whether patients benefit from chemotherapy if they have endocrine therapy onboard, number one? Also, there are a fair number of premenopausal women in this group, all of whom were having their ovaries shut down by the chemotherapy. So maybe this is an endocrine benefit that these patients are receiving.

Joyce A. O’Shaughnessy, MD: But that’s what was worrisome to me.

Adam M. Brufsky, MD: There wasn’t a benefit.

Joyce A. O’Shaughnessy, MD: There wasn’t a benefit.

Adam M. Brufsky, MD: There was a 25-year follow-up, and there was no benefit.

Joyce A. O’Shaughnessy, MD: In the luminal A’s.

Hope S. Rugo, MD: There should have been an endocrine benefit.

Joyce A. O’Shaughnessy, MD: Right. That’s what made me just not believe any of the data at all. Because where was the endocrine benefit from in this luminal A and this premenopausal high-risk group who were 5 cm or greater and node-positive? They were very high risk. They should have had an endocrine benefit. So the data just was not making internal consistency sense to me.

Hope S. Rugo, MD: And I think that the problem with some of those retrospective data sets is that you can be sort of waylaid. And so if you see something that’s inconsistent, you have to be really cautious in interpreting it.

Adam M. Brufsky, MD: I mean, I would agree with you. But on the other hand, the number of patients that was involved in this trial were the same that we use for the high-risk in OncotypeDx and in the SWOG Study.

Christy A. Russell, MD: 8814.

Adam M. Brufsky, MD: 8814 that we also use for node-positives with OncotypeDx.

Sara A. Hurvitz, MD: And not all women have their ovaries shut off by chemotherapy; that’s another point.

Adam M. Brufsky, MD: That’s another point. We’re assuming that they all were and it’s CMF and you know how old they are.

Sara A. Hurvitz, MD: Yeah, but you see a lot of patients who continue to have ovarian functions even though they’re amenorrheic after chemotherapy, now that we’re using GNRH analogs....

Hope S. Rugo, MD: Well, now chemotherapy, it’s very different, yeah. But I think if you gave oral CMF to anybody who was 35 or over, you’ve toasted their ovaries.

Adam M. Brufsky, MD: Well, we probably should move on—because we’ve got metastatic disease to talk about here—because we could go on for this forever. But the real question, Joyce, is maybe there’s some patients who don’t need anything.

Joyce A. O’Shaughnessy, MD: Well, I agree with that.

Adam M. Brufsky, MD: That’s the point, and maybe that’s what this says: that there’s someone who doesn’t need anything.

Joyce A. O’Shaughnessy, MD: Yeah, that’s what the TAILORx 10-and-under has said to me; maybe these are some cancers that really don’t have metastatic potential. It will be interesting to see the follow-up in years 6 through 10 of endocrine therapy presumably for most of them to see. Because so far, the retrospective low recurrent score grouping, you get out to a 6 to 10; gee, the data look terrific. You know in that strongly ER-positive, low-proliferative group…

Hope S. Rugo, MD: That stays up in the top.

Joyce A. O’Shaughnessy, MD: They just stay right up there.

Hope S. Rugo, MD: It’s just like one or two relapses away.

Joyce A. O’Shaughnessy, MD: And I stopped in the clinic. When I have one of those gals—whether I’ve had a recurrence score or whether they’re ER-PR really positive, really low proliferative, and node negative—they get to the end of that five years, I stop.

Hope S. Rugo, MD: Me, too.

Adam M. Brufsky, MD: So, there could be women that anatomically look terrible, right?

Hope S. Rugo, MD: Right.

Adam M. Brufsky, MD: You know: 5-cm tumor, 15 nodes positive.

Hope S. Rugo, MD: And they still relapse.

Adam M. Brufsky, MD: They relapse whether they enter therapy or not.

Hope S. Rugo, MD: It doesn’t matter.

Joyce A. O’Shaughnessy, MD: They have a poor prognosis, but they don’t benefit from therapy.

Adam M. Brufsky, MD: They don’t benefit from their interventions. Right?

Hope S. Rugo, MD: No, I don’t know that. I think that those patients benefit, in general, from endocrine therapy. I’m sure we can identify a group that are resistant and aren’t going to benefit. I think the question is that you may have a high risk of relapse, but chemotherapy may not alter that. And that’s the biggest issue. It’s kind of a tough situation from our standpoint because we look at these young women and we think, ‘I know you have a high relapse rate, but you have a low score and it’s a low-risk disease, but I’m still going to give you chemo.’ And we all do it because we don’t know that.

Adam M. Brufsky, MD: Because we’re treating ourselves. Are we treating the patient or are we treating ourselves?

Joyce A. O’Shaughnessy, MD: We’re waiting for the data, we’re waiting for the data.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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Transcript:

Adam M. Brufsky, MD:
I know people have been disagreeing with me about this since it came out, but I think one of the most fascinating papers at San Antonio this year was the presentation was by Nielsen.

Joyce A. O’Shaughnessy, MD: Oh.

Adam M. Brufsky, MD: So, who wants to take on that one? Christy, you want to describe the Nielsen paper because that gets to Hope’s question exactly of what to do.

Christy A. Russell, MD: So, the Nielsen paper was looking at whether the luminal A and luminal B, whether they’re actually predictive of benefit from chemotherapy. Because certainly a lot of people in the community say, ‘Well, I have a luminal A patient so they obviously won’t benefit from chemotherapy.’ It’s like, where are those data?

Adam M. Brufsky, MD: We have it.

Christy A. Russell, MD: So now we have a little bit of data.

Adam M. Brufsky, MD: A little bit.

Christy A. Russell, MD: Okay, fine.

Joyce A. O’Shaughnessy, MD: No endocrine therapy though.

Christy A. Russell, MD: When they did their presentation, they recognized that there are very few studies out there that have leftover blocks for which there’s long-term information about the patients, and they went back to a really old trial where patients either got cyclophosphamide/ methotrexate/ fluorouracil (CMF), Cytoxan, placebo, or no therapy at all.

Joyce A. O’Shaughnessy, MD: Levamisole.

Christy A. Russell, MD: Yeah. Levamisole.

Adam M. Brufsky, MD: It’s very, very old. We all are. Sara might be the only one here who’s not.

Christy A. Russell, MD: So they separated the groups. They showed the patients who got CMF and Cytoxan essentially did the same long term from the study and that the other groups didn’t do so well. So what it showed is that the luminal A’s did not seem to benefit from chemotherapy and that the luminal B’s, or everything else, including basal subtype and HER2, did seem to get some benefit from chemotherapy. Endocrine therapy was not used as a standard of care.

Adam M. Brufsky, MD: Because it wasn’t back then.

Christy A. Russell, MD: Right.

Adam M. Brufsky, MD: Back then, no one used endocrine therapy; it wasn’t standard of care 25 years ago.

Christy A. Russell, MD: But do you know whether patients benefit from chemotherapy if they have endocrine therapy onboard, number one? Also, there are a fair number of premenopausal women in this group, all of whom were having their ovaries shut down by the chemotherapy. So maybe this is an endocrine benefit that these patients are receiving.

Joyce A. O’Shaughnessy, MD: But that’s what was worrisome to me.

Adam M. Brufsky, MD: There wasn’t a benefit.

Joyce A. O’Shaughnessy, MD: There wasn’t a benefit.

Adam M. Brufsky, MD: There was a 25-year follow-up, and there was no benefit.

Joyce A. O’Shaughnessy, MD: In the luminal A’s.

Hope S. Rugo, MD: There should have been an endocrine benefit.

Joyce A. O’Shaughnessy, MD: Right. That’s what made me just not believe any of the data at all. Because where was the endocrine benefit from in this luminal A and this premenopausal high-risk group who were 5 cm or greater and node-positive? They were very high risk. They should have had an endocrine benefit. So the data just was not making internal consistency sense to me.

Hope S. Rugo, MD: And I think that the problem with some of those retrospective data sets is that you can be sort of waylaid. And so if you see something that’s inconsistent, you have to be really cautious in interpreting it.

Adam M. Brufsky, MD: I mean, I would agree with you. But on the other hand, the number of patients that was involved in this trial were the same that we use for the high-risk in OncotypeDx and in the SWOG Study.

Christy A. Russell, MD: 8814.

Adam M. Brufsky, MD: 8814 that we also use for node-positives with OncotypeDx.

Sara A. Hurvitz, MD: And not all women have their ovaries shut off by chemotherapy; that’s another point.

Adam M. Brufsky, MD: That’s another point. We’re assuming that they all were and it’s CMF and you know how old they are.

Sara A. Hurvitz, MD: Yeah, but you see a lot of patients who continue to have ovarian functions even though they’re amenorrheic after chemotherapy, now that we’re using GNRH analogs....

Hope S. Rugo, MD: Well, now chemotherapy, it’s very different, yeah. But I think if you gave oral CMF to anybody who was 35 or over, you’ve toasted their ovaries.

Adam M. Brufsky, MD: Well, we probably should move on—because we’ve got metastatic disease to talk about here—because we could go on for this forever. But the real question, Joyce, is maybe there’s some patients who don’t need anything.

Joyce A. O’Shaughnessy, MD: Well, I agree with that.

Adam M. Brufsky, MD: That’s the point, and maybe that’s what this says: that there’s someone who doesn’t need anything.

Joyce A. O’Shaughnessy, MD: Yeah, that’s what the TAILORx 10-and-under has said to me; maybe these are some cancers that really don’t have metastatic potential. It will be interesting to see the follow-up in years 6 through 10 of endocrine therapy presumably for most of them to see. Because so far, the retrospective low recurrent score grouping, you get out to a 6 to 10; gee, the data look terrific. You know in that strongly ER-positive, low-proliferative group…

Hope S. Rugo, MD: That stays up in the top.

Joyce A. O’Shaughnessy, MD: They just stay right up there.

Hope S. Rugo, MD: It’s just like one or two relapses away.

Joyce A. O’Shaughnessy, MD: And I stopped in the clinic. When I have one of those gals—whether I’ve had a recurrence score or whether they’re ER-PR really positive, really low proliferative, and node negative—they get to the end of that five years, I stop.

Hope S. Rugo, MD: Me, too.

Adam M. Brufsky, MD: So, there could be women that anatomically look terrible, right?

Hope S. Rugo, MD: Right.

Adam M. Brufsky, MD: You know: 5-cm tumor, 15 nodes positive.

Hope S. Rugo, MD: And they still relapse.

Adam M. Brufsky, MD: They relapse whether they enter therapy or not.

Hope S. Rugo, MD: It doesn’t matter.

Joyce A. O’Shaughnessy, MD: They have a poor prognosis, but they don’t benefit from therapy.

Adam M. Brufsky, MD: They don’t benefit from their interventions. Right?

Hope S. Rugo, MD: No, I don’t know that. I think that those patients benefit, in general, from endocrine therapy. I’m sure we can identify a group that are resistant and aren’t going to benefit. I think the question is that you may have a high risk of relapse, but chemotherapy may not alter that. And that’s the biggest issue. It’s kind of a tough situation from our standpoint because we look at these young women and we think, ‘I know you have a high relapse rate, but you have a low score and it’s a low-risk disease, but I’m still going to give you chemo.’ And we all do it because we don’t know that.

Adam M. Brufsky, MD: Because we’re treating ourselves. Are we treating the patient or are we treating ourselves?

Joyce A. O’Shaughnessy, MD: We’re waiting for the data, we’re waiting for the data.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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