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Risk of Early Versus Late Recurrence

Insights From:Ruth O’Regan, MD, University of Wisconsin;Hope S. Rugo, MD, UCSF
Published: Friday, Nov 04, 2016


Transcript:

Hope S. Rugo, MD:
So, based on the data that we have now, we do understand that there are specific clinical factors that increase the risk of late recurrence. We have data, actually, from a fascinating meta-analysis from the early breast cancer clinical trials group that was presented at ASCO, that looked at variation in risk of recurrence between years 5 and 20 in women who had received 5 years of tamoxifen therapy. Meta-analyses and looking retrospectively at data are obviously going to have some inherent flaws, but what was fascinating was that even women who had stage I cancers had some risk of distant recurrence, higher than we would have thought. When you go back and look at that, we know that some of those women had HER2–positive disease, and some of the information about ER positivity may not have been correct. But, if you looked at the women who had node-positive breast cancer—particularly higher-stage cancers, larger T sizes, and larger number of positive nodes—those risks were much higher. And, it was true for women who had higher-grade tumors, as well. I think that if we combine it together, it’s higher stage and higher grade that really put women at a higher risk of late recurrence.

In addition, I think the advent of genomic tests that look at gene expression and gene expression signatures will help us. I believe they’re going to help us in the future, in terms of identifying the women who have continued higher risk of recurrence and are likely to benefit from ongoing aromatase inhibitor therapy.

I think we do understand, now that there is a group of women whose tumor characteristics allow them to forego extended adjuvant hormone therapy. And, as we’ve been discussing, these women tend to have lower-stage cancers. The cancers are lower grade. If you just wanted to pick out specific features, these would be patients who are generally older, have lower-grade tumors, T1, node negative. Even young women who have very small cancers don’t have a clearly increased risk of late recurrence, so, I think that those women also should be taken into account. And, it’s particularly important in women who have interest in fertility and, of course, are trying to live their lives at a very young age. I think that the genomic tests are going to help us with this as well. There are genomic tests that you can obtain in patients, either at the time of diagnosis or at 5 years, that may help us a little bit in terms of understanding residual risk because the genomics will play a role. If you’re at low risk by genomics, you’re going to have a lower risk after 5 years, as well, but there’s a counteraction with the actual volume of tumor. It’s going to always play a role how much cancer you have, even if you have this low risk by genomics. So, you have to take both into account.

Ruth O’Regan, MD: As far as the risk of late recurrence, I’m not sure that we really know whether it changes over time or not. I think the problem is that we have molecular assays that can predict risk when a patient’s diagnosed, and molecular assays that can predict risk that’s likely to occur later on. But, I don’t think we’ve ever really done a particular analysis to see if the risk changes an individual patient over time. I’m not really sure how we would do that. But, I think we are gaining, over the past year or so, quite a bit of data using molecular assays that indicate there are patients with estrogen receptor–positive breast cancers who have an incredibly low rate of recurrence, both on the short follow-up end, and also the longer end. I think that’s information that we’re gathering.

Now, if we have data saying that they’ve got a low risk of recurrence up to 10 years, I don’t think we know what happens after 10 years. So, it is possible that there may be a slight increased risk in some patients. But, I think, in individual patients, the biology probably predicts the late recurrence rate, and you can probably tell from the time the patient is diagnosed.

Transcript Edited for Clarity
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Transcript:

Hope S. Rugo, MD:
So, based on the data that we have now, we do understand that there are specific clinical factors that increase the risk of late recurrence. We have data, actually, from a fascinating meta-analysis from the early breast cancer clinical trials group that was presented at ASCO, that looked at variation in risk of recurrence between years 5 and 20 in women who had received 5 years of tamoxifen therapy. Meta-analyses and looking retrospectively at data are obviously going to have some inherent flaws, but what was fascinating was that even women who had stage I cancers had some risk of distant recurrence, higher than we would have thought. When you go back and look at that, we know that some of those women had HER2–positive disease, and some of the information about ER positivity may not have been correct. But, if you looked at the women who had node-positive breast cancer—particularly higher-stage cancers, larger T sizes, and larger number of positive nodes—those risks were much higher. And, it was true for women who had higher-grade tumors, as well. I think that if we combine it together, it’s higher stage and higher grade that really put women at a higher risk of late recurrence.

In addition, I think the advent of genomic tests that look at gene expression and gene expression signatures will help us. I believe they’re going to help us in the future, in terms of identifying the women who have continued higher risk of recurrence and are likely to benefit from ongoing aromatase inhibitor therapy.

I think we do understand, now that there is a group of women whose tumor characteristics allow them to forego extended adjuvant hormone therapy. And, as we’ve been discussing, these women tend to have lower-stage cancers. The cancers are lower grade. If you just wanted to pick out specific features, these would be patients who are generally older, have lower-grade tumors, T1, node negative. Even young women who have very small cancers don’t have a clearly increased risk of late recurrence, so, I think that those women also should be taken into account. And, it’s particularly important in women who have interest in fertility and, of course, are trying to live their lives at a very young age. I think that the genomic tests are going to help us with this as well. There are genomic tests that you can obtain in patients, either at the time of diagnosis or at 5 years, that may help us a little bit in terms of understanding residual risk because the genomics will play a role. If you’re at low risk by genomics, you’re going to have a lower risk after 5 years, as well, but there’s a counteraction with the actual volume of tumor. It’s going to always play a role how much cancer you have, even if you have this low risk by genomics. So, you have to take both into account.

Ruth O’Regan, MD: As far as the risk of late recurrence, I’m not sure that we really know whether it changes over time or not. I think the problem is that we have molecular assays that can predict risk when a patient’s diagnosed, and molecular assays that can predict risk that’s likely to occur later on. But, I don’t think we’ve ever really done a particular analysis to see if the risk changes an individual patient over time. I’m not really sure how we would do that. But, I think we are gaining, over the past year or so, quite a bit of data using molecular assays that indicate there are patients with estrogen receptor–positive breast cancers who have an incredibly low rate of recurrence, both on the short follow-up end, and also the longer end. I think that’s information that we’re gathering.

Now, if we have data saying that they’ve got a low risk of recurrence up to 10 years, I don’t think we know what happens after 10 years. So, it is possible that there may be a slight increased risk in some patients. But, I think, in individual patients, the biology probably predicts the late recurrence rate, and you can probably tell from the time the patient is diagnosed.

Transcript Edited for Clarity
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