Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementRole of neoadjuvant endocrine therapy and chemotherapy for premenopausal patients with ER-positive BC
5:24 minutes.
TRANSCRIPTION:
DR LOVE: So this doc actually had another case, very similar, again the surgeon sent to her to try to shrink it down. This is a 45-year-old lady, ER-positive, HER2-negative tumor, but it was a ductal carcinoma. So basically the same kind of question in terms of genomic assays to try to decide if you want to shrink this tumor down to help with breast-conserving surgery. Should you consider endocrine therapy? Should you consider a genomic assay? DR O’SHAUGHNESSY: As I mentioned, in the younger women, the premenopausals — now, 45, if you give chemotherapy, they’re going to shut their ovaries down pretty quickly. So you can argue you may not need an LHRH agonist to get those ovaries down. If she were younger, I would be using endocrine therapy along with chemotherapy right away. I would say, Neil, there is a small group of the women in their forties, for example, who have very indolent — sometimes it’s even Grade 1 or it’s Grade 2 with a very low Ki-67, 100% ER, 100% PR, HER2 zero. And you’re looking at that, going, “Wow! The role of chemotherapy here is going to probably be more about ovarian ablation than it is direct cytoreduction.” So there is a group. But if my job is to get that cancer shrunk down so that that woman has the opportunity for breast-conserving surgery in addition to curing her of her breast cancer, then I’m certainly going to be thinking about endocrine therapy sooner than later for her. There are patients, Neil — it’s a small percentage, but there are patients that I don’t give chemotherapy to. I’ll just go with even preoperative endocrine therapy. Of course I’ll optimize it. There’ll be an LHRH agonist in there, and I can start with tamoxifen. It’s a ductal cancer and it’s indolent. You can start with tamoxifen, allow the woman to see how she does, see if she responds well. I think even though the data from the SOFT and TEXT did not show any difference in quality of life between LHRH agonist and tamoxifen versus the aromatase inhibitor, most of us don’t see that in practice. Most of us see that it’s very difficult with the LHRH agonist plus an aromatase inhibitor right away, up front in a premenopausal woman. It’s easier to transition from LHRH agonist/tamoxifen for a while, for a year or so before switching over, in order to be able to accomplish the goal. But I would individualize, Neil. I do take the biology into account. DR LOVE: It’s interesting. We did a survey last year and actually had a poster at San Antonio where one of the things we saw was that not a small number of investigators were using genomic assays, mainly the 21-gene Recurrence Score, in the neoadjuvant setting. And others have said, “Where’s the data?” But there was a poster – I don't know if you saw it – at San Antonio. Harry Bear has had this study looking at neoadjuvant therapy, utilizing the Recurrence Score. And actually, Denise Yardley had some data looking at this. And it kind of looks like path CR — response rate, path CR, response rate, et cetera, I think, looking at those 2 studies. It seems like it does correlate with at least the 21-gene Recurrence Score. What’s your take on that? DR O’SHAUGHNESSY: And remember the original Luca Gianni trial, Neil, from a lot of years ago with the anthracycline/taxane-based preoperative regimen. And it really was true. You saw very few, if any, path CRs in the lower. But when you got into the high Recurrence Scores, you started to pick up path CRs. The issue, though, in the ER-positive patient isn’t really path CR. It’s really getting cytoreduction, so she can have surgery she wants. DR LOVE: Right. DR O’SHAUGHNESSY: And secondly, curing her up of her breast cancer, basically. So, that’s where the issue is: Is it safe to leave chemotherapy off of these patients? That’s really what we’re talking about here. And we don’t have enough data yet, particularly when you’re getting into patients with, like, nodes positive. In the neoadjuvant setting, unless you do a sentinel lymph node up front, you don’t really know what your nodal status is, et cetera. I don’t think we have enough data yet in most premenopausal, ER-positive, either larger cancers or node-positive cancers to leave chemotherapy off most of those patients, because really, if you’re in the adjuvant setting when you have all the data in front of you, you know exactly how large it is. You know the nodal status. You know on your Ki-67 whether there’s heterogeneity, because when they read the Ki-67s, they’ll say, “Oh, 10% to 15%, but there’s focally areas up to 25%, 30%.” Those are your lethal subclones. And when you’re just doing a little needle biopsy up front, you don’t have all the answers there, basically. So I’m fairly cautious. Having said that, there is the occasional patient that has the anatomic and biologic features that I’d be comfortable starting with endocrine therapy alone, knowing I’m going to get more data at surgery. |