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Adjuvant Therapy for HR+ Breast Cancer

Panelists: Joyce O Shaughnessy, MD, Baylor University Medical Center; Kevin Kalinsky, MD, MS NewYork-Presbyterian Hospital; Elizabeth Mittendorf Dana-Farber; Ruth O Regan, MD, University of Wisconsin Carbone Cancer Center; Hope S. Rugo, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Published: Friday, May 03, 2019



Transcript:

Joyce O’Shaughnessy, MD:
To finish up this part, in terms of the younger premenopausal woman with node-negative disease, and she comes back in that intermediate range on the recurrence score and she’s under age 50, and I think you alluded to it, it was not knowing whether an LHRH [luteinizing hormone-releasing hormone] agonist plus endocrine therapy would be just as good as chemotherapy. How do you parse that out in your practice, Ruth?

Ruth O'Regan, MD: Well, I think it’s really a patient-by-patient case. I actually use the table from TAILORx a lot in that group to show them what their benefit is. Again, I just don’t think the report really gives as much data as we would want. So that’s essentially how I approach it. I’ve had several of them who were actually waiting for TAILORx to come out. Several patients were basically saying, “I’m not doing it.” I gave them an ovarian suppression with endocrine therapy, and hopefully they’ll do just fine with that. But I think it’s a very important question. We know of Meredith Regan, ScD’s, composite risk score, which would appear to align with the recurrence score and would suggest that it’s only when you’ve got these patients who are at high composite risk, they’re the patients who benefit from ovarian suppression plus endocrine therapy, which will be similar to patients with higher recurrence scores. Whereas as the lower recurrence scores, somebody who has the lower risk score, they do not appear to benefit from the additional ovarian suppression. So I think that will be very interesting to use in these patients.

Joyce O’Shaughnessy, MD: Yes. How about you, Kevin?

Kevin Kalinsky, MD, MS: I had a patient who was receiving chemotherapy and then the TAILORx results came out. And then she said, “Well, I think I’m done.”

The other thing that I wanted to say, which is maybe a little bit off topic, but in terms of our RxPONDER study, there are other platforms as well, for sickness platform, etcetera. And embedded in RxPONDER, when the primary outcome is reported, embedded in the translational medicine section, we will hopefully be looking at other platforms and how they compare to the recurrence scores. So it would be nice to see, in terms of the differences in prediction, in a randomized study how they compare.

Joyce O’Shaughnessy, MD: Who do you give ovarian suppression to? In the node-negative setting, coming out of TAILORx, for example, is it 16 to 20 [recurrence score], and then above 20 you tend to do chemotherapy?

Kevin Kalinsky, MD, MS: I think that those patients who had a score of 21 to 25, when we looked at that distant disease-free event—that 6% or so—I think that’s a meaningful number, so I tend to give those patients chemotherapy. In a node-negative patient, it becomes a bit tricky in terms of who to give ovarian suppression to. In my practice, I remain a bit concerned about the long-term ramifications of giving ovarian suppression. And certainly there are data in terms of those patients who are less than 35. But it tends to be a patient-by-patient situation, in terms of determination for the node-negatives and who I give ovarian suppression to.

Joyce O’Shaughnessy, MD: How about you, Hope?

Hope S. Rugo, MD: I really agree with both Kevin and Ruth. I think that for the patients who have node-positive disease or larger tumors, higher-grade tumors, I tend to use ovarian suppression across the board. I have always been a big believer, and then of course the TEXT and SOFT trials fit right in to what I believe. So that’s very helpful. For people who have small tumors and very low scores, I think tamoxifen is fine. These are premenopausal women, so I wouldn’t feel comfortable with no treatment. I think tamoxifen is a very reasonable approach and it actually gives them a little bit of that estrogen-like effect, so they don’t feel as bad and don’t have as much depression, mostly, but not always. Tamoxifen can be tough too. But I do use a lot of ovarian suppression in higher-risk, younger women, and particularly those women who are under the age of 40.

Joyce O’Shaughnessy, MD: How about chemotherapy for that intermediate-risk group above 16 to 25? What do you?

Hope S. Rugo, MD: I wasn’t as impressed with the 16 to 20, but I agree with Kevin that for that group of patients who had a 6% difference in distant disease-free survival, OK, that’s good. I’m going to give chemotherapy to those people. But if you had a score that was 23 and the patient had a 0.4-cm tumor and somebody had sent it, I’m not going to give chemotherapy. But, for most patients, if they have a T1c tumor and they’re young, I think most of us would probably err on the side of at least discussing chemotherapy and considering treatment for a young woman.

Joyce O’Shaughnessy, MD: Yes, it sounds like a lot of consensus there.

Ruth O'Regan, MD: I would agree. I think the other thing, just to go back to the over age 50 population, I guess I’d be interested to think or hear what people do with patients who are over age 50 and have a recurrence score of 27? Because you cannot imagine that they get a lot of benefit from chemotherapy, which is why the NCCN [National Comprehensive Cancer Network] guidelines are written the way they are. So I think that’s another group for whom I suspect they’re getting a lot of chemotherapy for very little benefit.

Hope S. Rugo, MD: Although there can’t be a magic differential at the age of 50.

Joyce O’Shaughnessy, MD: Yes, it’s a patient-by-patient thing.

Ruth O'Regan, MD: I’m talking about if you were an older patient with a score of 28.

Joyce O’Shaughnessy, MD: I agree.

Ruth O'Regan, MD: I miss the continuous nature of the original report, because the report now says your benefit is 15% if it’s over 25, and you’re saying to patients, “Well, no. Not with the score you have.”

Hope S. Rugo, MD: It’s hard. I had a young woman who had a 0.8-cm tumor and a score of 50-something, and she just panicked. Of course she got chemotherapy and then came to us as her insurance changed. But it was such a horrible panic for her with such a tiny cancer. I felt really badly because it’s very hard to undo that.

Joyce O’Shaughnessy, MD: Yes. And hopefully it’s like the high-2, where she’ll get an excellent response from chemotherapy with those real full throttle cancer medicines.

Hope S. Rugo, MD: And ovarian suppression.

Joyce O’Shaughnessy, MD: And ovarian suppression, absolutely.


Transcript Edited for Clarity

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Transcript:

Joyce O’Shaughnessy, MD:
To finish up this part, in terms of the younger premenopausal woman with node-negative disease, and she comes back in that intermediate range on the recurrence score and she’s under age 50, and I think you alluded to it, it was not knowing whether an LHRH [luteinizing hormone-releasing hormone] agonist plus endocrine therapy would be just as good as chemotherapy. How do you parse that out in your practice, Ruth?

Ruth O'Regan, MD: Well, I think it’s really a patient-by-patient case. I actually use the table from TAILORx a lot in that group to show them what their benefit is. Again, I just don’t think the report really gives as much data as we would want. So that’s essentially how I approach it. I’ve had several of them who were actually waiting for TAILORx to come out. Several patients were basically saying, “I’m not doing it.” I gave them an ovarian suppression with endocrine therapy, and hopefully they’ll do just fine with that. But I think it’s a very important question. We know of Meredith Regan, ScD’s, composite risk score, which would appear to align with the recurrence score and would suggest that it’s only when you’ve got these patients who are at high composite risk, they’re the patients who benefit from ovarian suppression plus endocrine therapy, which will be similar to patients with higher recurrence scores. Whereas as the lower recurrence scores, somebody who has the lower risk score, they do not appear to benefit from the additional ovarian suppression. So I think that will be very interesting to use in these patients.

Joyce O’Shaughnessy, MD: Yes. How about you, Kevin?

Kevin Kalinsky, MD, MS: I had a patient who was receiving chemotherapy and then the TAILORx results came out. And then she said, “Well, I think I’m done.”

The other thing that I wanted to say, which is maybe a little bit off topic, but in terms of our RxPONDER study, there are other platforms as well, for sickness platform, etcetera. And embedded in RxPONDER, when the primary outcome is reported, embedded in the translational medicine section, we will hopefully be looking at other platforms and how they compare to the recurrence scores. So it would be nice to see, in terms of the differences in prediction, in a randomized study how they compare.

Joyce O’Shaughnessy, MD: Who do you give ovarian suppression to? In the node-negative setting, coming out of TAILORx, for example, is it 16 to 20 [recurrence score], and then above 20 you tend to do chemotherapy?

Kevin Kalinsky, MD, MS: I think that those patients who had a score of 21 to 25, when we looked at that distant disease-free event—that 6% or so—I think that’s a meaningful number, so I tend to give those patients chemotherapy. In a node-negative patient, it becomes a bit tricky in terms of who to give ovarian suppression to. In my practice, I remain a bit concerned about the long-term ramifications of giving ovarian suppression. And certainly there are data in terms of those patients who are less than 35. But it tends to be a patient-by-patient situation, in terms of determination for the node-negatives and who I give ovarian suppression to.

Joyce O’Shaughnessy, MD: How about you, Hope?

Hope S. Rugo, MD: I really agree with both Kevin and Ruth. I think that for the patients who have node-positive disease or larger tumors, higher-grade tumors, I tend to use ovarian suppression across the board. I have always been a big believer, and then of course the TEXT and SOFT trials fit right in to what I believe. So that’s very helpful. For people who have small tumors and very low scores, I think tamoxifen is fine. These are premenopausal women, so I wouldn’t feel comfortable with no treatment. I think tamoxifen is a very reasonable approach and it actually gives them a little bit of that estrogen-like effect, so they don’t feel as bad and don’t have as much depression, mostly, but not always. Tamoxifen can be tough too. But I do use a lot of ovarian suppression in higher-risk, younger women, and particularly those women who are under the age of 40.

Joyce O’Shaughnessy, MD: How about chemotherapy for that intermediate-risk group above 16 to 25? What do you?

Hope S. Rugo, MD: I wasn’t as impressed with the 16 to 20, but I agree with Kevin that for that group of patients who had a 6% difference in distant disease-free survival, OK, that’s good. I’m going to give chemotherapy to those people. But if you had a score that was 23 and the patient had a 0.4-cm tumor and somebody had sent it, I’m not going to give chemotherapy. But, for most patients, if they have a T1c tumor and they’re young, I think most of us would probably err on the side of at least discussing chemotherapy and considering treatment for a young woman.

Joyce O’Shaughnessy, MD: Yes, it sounds like a lot of consensus there.

Ruth O'Regan, MD: I would agree. I think the other thing, just to go back to the over age 50 population, I guess I’d be interested to think or hear what people do with patients who are over age 50 and have a recurrence score of 27? Because you cannot imagine that they get a lot of benefit from chemotherapy, which is why the NCCN [National Comprehensive Cancer Network] guidelines are written the way they are. So I think that’s another group for whom I suspect they’re getting a lot of chemotherapy for very little benefit.

Hope S. Rugo, MD: Although there can’t be a magic differential at the age of 50.

Joyce O’Shaughnessy, MD: Yes, it’s a patient-by-patient thing.

Ruth O'Regan, MD: I’m talking about if you were an older patient with a score of 28.

Joyce O’Shaughnessy, MD: I agree.

Ruth O'Regan, MD: I miss the continuous nature of the original report, because the report now says your benefit is 15% if it’s over 25, and you’re saying to patients, “Well, no. Not with the score you have.”

Hope S. Rugo, MD: It’s hard. I had a young woman who had a 0.8-cm tumor and a score of 50-something, and she just panicked. Of course she got chemotherapy and then came to us as her insurance changed. But it was such a horrible panic for her with such a tiny cancer. I felt really badly because it’s very hard to undo that.

Joyce O’Shaughnessy, MD: Yes. And hopefully it’s like the high-2, where she’ll get an excellent response from chemotherapy with those real full throttle cancer medicines.

Hope S. Rugo, MD: And ovarian suppression.

Joyce O’Shaughnessy, MD: And ovarian suppression, absolutely.


Transcript Edited for Clarity
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