DR LOVE: A 41-year-old lady has a 1.6-cm, ER-positive, HER2-negative tumor. And she has a 1-cm biopsy-proven axillary node. She also has a Ki-67 of 50%. So we asked the audience, what would you do in a situation like that? And, of course, we asked the faculty, too. And the audience was kind of split. About half the audience said, “I would send her to surgery even with the positive node.” And the other half, most of them said chemo, but there were about 10% of people who said, “I’d want to do a genomic assay, 21-gene Recurrence Score.”

So I’m kind of curious. How do you generally approach the question of neoadjuvant therapy in ER-positive, HER2-negative? And what do you think about this specific case scenario?

DR O'SHAUGHNESSY: In her case, Neil, I would not order a genomic assay, because nothing, honestly, would deter me away from the standard pathologic variables, with the positive node and the high Ki-67.

The issue of preoperative versus postoperative is interesting, because although all the randomized trials showed no difference in disease-free or overall survival with pre- or postoperative, there’s that intriguing subset analysis from B-17 in young women under the age of 50 who received preoperative versus postoperative. And their outcome was better in the preoperative setting.

There are other data that say that getting going with chemotherapy for, for example, triple-negative breast cancer within 30 days of surgery improves outcome. So when you have a very highly proliferative cancer, the thing is, sometimes these young women will proceed to bilateral mastectomy and expander reconstruction. You’re 6 weeks down the road, 8 weeks down the road by the time you get all the doctors on board. So in this particular case, I may have been inclined to get going.

Now, I treat these patients with the TEXT trial. I utilize an LHRH agonist right along with the chemotherapy. The SOFT trial, as you know, used the LHRH agonist after the chemotherapy, once they had proven that the women were still premenopausal after chemotherapy. But the TEXT trial utilized LHRH agonist along with the chemotherapy. And I do that, because I believe that the antiestrogen therapies are the most important, of course, as we all do, for ER-positive breast cancer. And I don’t want to wait 5 months before getting the antiestrogen therapy going for these patients.

Now, in a 41-year-old, the AC will turn off the ovaries over time, but it may be several cycles, et cetera. So I like to get the LHRH agonist going. So in this particular woman, I might be inclined to utilize preoperative chemotherapy for her with an LHRH agonist.

DR LOVE: Maybe I could add to that rationale by saying even though she has a biopsy-proven axillary node, if, in the maybe not-that-likely situation she had a clinical CR, potentially would she, in your hands, maybe avoid axillary node dissection?

DR O'SHAUGHNESSY: Yes. Yes, or at least less. And I think surgeons, if patients have a phenomenal response, are more willing to do a sentinel lymph node, maybe not take out 1, but take out 3 or 4, if they can. And then if it’s all negative, stop. It’s a controversial thing about — let’s say she is a pathologic complete response. Does she still need post-mastectomy radiation? Obviously if she has a lumpectomy, that’s easy. You would probably utilize local-regional radiation therapy, as in MA.20, where the 1 to 3 node-positive patients had an improvement in their overall outcome with radiation therapy to the regional lymphatics.

With aggressive biology, I have been still recommending postmastectomy radiation even if somebody has had a pathologic complete response, because there are randomized trials going on looking at that question to see if they need it or not. But in the meantime, I do still consider it the standard of care for aggressive biology, young woman, 1 to 3 positive lymph nodes.

DR LOVE: So, actually, in fact, this patient got neoadjuvant chemotherapy and had a response but still had residual disease at surgery. And actually, the doc discussed the CREATE-X trial with the patient in terms of postneoadjuvant capecitabine. And, actually, he wasn’t very excited about it, because she was ER-positive, but the patient wanted it. And so he was willing to give capecitabine, but his question was, how do you integrate capecitabine, then, into the postoperative management in terms of, for example, radiation therapy as well as hormonal therapy?

DR O’SHAUGHNESSY: Interestingly, Neil, I just want to make the point. It’s interesting, because the CREATE-X, of course, was an overall positive trial. The subset analysis really showed that the majority of the benefit was in the triple-negative. But what’s tricky about that is that when you look at the estrogen receptor-positive subset, the numbers are too small to really tease out the more indolent ER-positives from the more aggressive ER-positives.

Now, in the CREATE-X trial, what they did is that they did the radiation therapy first, and then they did 6 months of capecitabine afterwards. Of course you can start your endocrine therapy as we standardly do right after chemotherapy. You can get going on that. I like to get it going fairly quickly. I give it during the radiation therapy. It’s just a very important systemic treatment.

DR LOVE: But you’re saying you would give hormonal therapy and capecitabine together?

DR O’SHAUGHNESSY: Yes, I would. I would. Yes. I do.

DR LOVE: Just to finish out on this, what about the dose of capecitabine?

DR O’SHAUGHNESSY: I utilize the 1,000 mg/m² BID, 14/7. I believe the CREATE-X used the full dose. I believe they used the 2,500.

DR LOVE: Right. That’s why I was asking you. Yes.

DR O’SHAUGHNESSY: In the US, that’s been difficult to achieve. You can start there, but most patients require a dose reduction. It’s just been interesting, different places around the world, different people have different tolerability of the full dose versus a somewhat reduced dose. So I think the 2 grams/m² has become more standard in the US. That’s what I use.

Adjuvant and neoadjuvant therapy for HER2-positive breast cancer (BC)

Management of HER2-positive metastatic BC (mBC)

Clinical decision-making for patients with ER-positive early BC

Management of ER-positive, HER2-negative mBC

Indications for BRCA testing in BC and ongoing investigation of PARP inhibition

Treatment of triple-negative BC (TNBC)