Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementUse of genomic assays to predict benefit from extended endocrine therapy in ER-positive, HER2-negative BC
7:18 minutes.
TRANSCRIPTION:
DR LOVE: So the next issue we got into with a case of a 63-year-old woman was the question of extending endocrine therapy at 5 years. And first we kind of altered the case a little bit and presented it to the audience. And I’ll tell you how we altered it. Sixty-three-year-old woman, originally has a 1.5-cm node-negative, ER-positive, HER2-negative tumor, gets TC times 4 followed by anastrozole for 5 years. She’s never had a genomic assay. Now she’s at 5 years. She’s tolerating the anastrozole well. And we asked the audience in general, “What would you do?” So most of the audience — I’m sure because it was node-negative — said, “We’d stop the therapy.” But there was a fraction, maybe a quarter of the audience, who would use some type of genomic assay, mainly actually the Breast Cancer Index at that point, to make a decision. How would you think through a case like this? DR O’SHAUGHNESSY: I would go back to the biology initially on the patient. And I would kind of extrapolate a bit, though we don’t have a Recurrence Score in hand, for example, Neil. If the patient’s breast cancer initially was strongly ER/PR-positive, Grade 1 or 2, with a low Ki-67 — because I would have a Ki-67 on her — I would have a pretty high level of confidence that, had I had a Recurrence Score up front, that she would have been in a low Recurrence Score category. And I definitely would stop her therapy. I would extrapolate from the TAILORx even though the only data we have so far is the 1 to 10, the very, very low Recurrence Scores. But all the data, I’m impressed that the low Recurrence Score data, particularly in the strongly ER-positive, really predicts for a superb outcome after 5 years of endocrine therapy. So I’m really becoming increasingly confident of that. Conversely, if the woman’s cancer was more weakly estrogen receptor-positive, progesterone receptor-negative or weak, with a higher grade, Grade 3, higher Ki-67 — also, Neil, if she had a family history, if she still has intact breast tissue, so she’s at risk down the road again for another breast cancer, those would all be factors in my thinking from her. The recent data presented by Pan and colleagues from the Oxford Overview analysis group, going out now 20 years and looking at patients who had had 5 years of endocrine therapy and then just looking strictly at anatomic and characteristics, tumor size, nodal status and grade, really gave us pretty good estimates. I have that with me in the room now. I estimate for the woman over the next 15 years, from years 6 through 20, what’s her risk of breast cancer recurrence. And the numbers came out a little bit higher than I think a lot of us anticipated. But I do look at the biology, too. Sometimes if a woman really wants all the information possible, though we have still somewhat limited data with these assays, I have ordered the Breast Cancer Index. And if it does really come back low — and again, I like it to be consonant with what I was looking at biologically. It’s another piece of evidence — I probably wouldn’t send it, though, Neil, honestly, if the biologic characteristics of the cancer were quite adverse and somebody had a T1 or a T2N0 but it was an aggressive cancer. I would just say to the woman, “That can be just as high-risk as having 1 to 3 nodes positive.” No question about it. So I would recommend, if she were otherwise tolerating it well, et cetera, I would just say to stay on the aromatase inhibitor. And that was the bottom line I took away from San Antonio this year, is that the decision around who to extend the endocrine therapy, the adjuvant endocrine therapy on is going to come down to just level of risk, the absolute risk that the woman has going forward after the first 5 years. And as we get into the node-positive and more biologically aggressive node-negative patients, we’re going to really end up recommending staying on it, but in biologically indolent disease, particularly node-negative, not. DR LOVE: So no case is ever that straightforward. And the actual case that was presented by one of the docs — actually came down to the booth and presented it — same situation, 63-year-old woman, 1.5-cm node-negative tumor. But the actual case, the patient was not only ER-positive but HER2-positive. And the patient got chemo and trastuzumab adjuvant therapy and then got the anastrozole. So then the question is, how does the HER2 play into this decision about extending endocrine therapy 5 years? In your own practice, how does it work? DR O’SHAUGHNESSY: As you know, Neil, the ER-positive, HER2-positive group is heterogeneous. There’s luminal As in that group and there’s luminal Bs. And you’ll even find some HER2-enriched in that group, and it depends on the level of the estrogen receptor, progesterone receptor, the level of the HER2 amplification. And it depends on the Ki-67, the grade. So it’s the whole biologic property. If a woman has very strongly ER/PR-positive breast cancer that is very indolent, node-negative, but again, it’s very indolent Grade 2 disease, let’s say, I would consider her very likely to be a luminal A. And that might be a situation, Neil, where I might want to send a Breast Cancer Index or potentially a PAM50 and see if she really does come back luminal A. Because Lisa Carey and colleagues have really nicely shown that there’s definitely some of these ER-positive, HER2-positives that are luminal A biology. So I might really send one of the assays there to really understand if what I’m seeing with the standard pathologic characteristics really do predict for very indolent biology that really isn’t HER2 driven. Conversely, though, if it really appears to be more of a HER2-driven, weaker ER, more highly proliferative, I err on the side of recommending continuing endocrine therapy beyond 5 years, because we’ve seen in the NSABP B-31 as you go out beyond 5 years that the ER-positive, HER2-positive patients continue to have a steady rate of recurrence after 5 years, going out from years 5 to 10. They still recur just like we’ve always seen with ER-positive disease. So I would individualize, Neil. |