Cases from the Community: Investigators Provide Their Perspectives on the Practice Implications of Emerging Clinical Research — A Special Video SupplementCase discussion: A 60-year old woman with previously treated mTNBC presents with a painful sternal metastasis
10:13 minutes.
TRANSCRIPTION:
DR LOVE: So there was another case that I remember that you commented on at the meeting. This is a case presented by Dr Alan Astrow, a 60-year-old woman who had a history of a metastatic triple-negative breast cancer. But, interestingly, the main problem was a sternal metastasis. She really didn’t have disease outside. He utilized radiation therapy, multiple chemotherapies. The lesion was painful for her, a big lesion. And he actually sent the woman finally to a university center where it was resected. A pretty big operation. They got R0 margin. The patient was about 6 weeks postop at the time of San Antonio when he presented it, so he was cautiously optimistic that it had been successful. She was recovering from her surgery. But he was curious — there were a couple of questions he had. One was whether anybody had any experience with this and whether what he did was justified. And I remember I was really shocked and surprised that you had a lot of experience with this. DR SMITH: We do. And we’ve published on this. We’ve published twice, first with about 20 patients and now with about 40 patients. You need to remind me and I’ll send you the second paper. The reason we got into this is one of life’s serendipity. We are right next door to the Royal Brompton Hospital in London, which is the top specialist thoracic hospital in the country dealing with lung and heart disease. So we have the best thoracic surgeons. And our reconstructive surgeons work with them to do these resections, because we’re not talking minor surgery here. These are often 7-, 8-hour procedures. Obviously the patient needs to be staged first. And we would do PET/CT scan staging. It’s the most sensitive way of excluding disease elsewhere. And we’ve got very good long-term results with the outcome for most of these patients measured in years rather than months. So that’s certainly what we would do. And we’re a big fan of the approach. And maybe — I was a little surprised that it wasn’t more of a standard. And I think we perhaps need to emphasize our results or try and get a little bit more publicity. Perhaps this conversation we’re having now might stimulate people, because it really is an effective treatment. DR LOVE: Yes. I was surprised that you had seen so many cases. And I was wondering what the pathophysiology here is, because, for example, this patient, this has gone on for years without disease outside of that area. Do you think that this is really just a local extension? DR SMITH: I think they arise from internal mammary node and then they just grow directly into the sternum. And once they’re in the bone, somehow they can spread easily through the marrow of the sternum. DR LOVE: Yes. Actually, he told me that there was a pretty significant soft tissue mass. DR SMITH: There’s always a soft tissue component there. And I think it’s coming from the internal mammary. Now, why they should just have 1 node — because you would imagine, if you resected this — when we began this, we thought, “It’s probably not going to work for very long, because metastases will pop up all over the place,” but the answer is, more often than not, they don’t seem to. DR LOVE: So another question that Dr Astrow had about this patient is, he’s going to be following her now — a concern that she might have progressive disease at some point. She’s been through every possible chemotherapy, I think, that you can imagine and was curious about a number of possibilities for the future for her if she does have disease progression, triple-negative disease, the first being checkpoint inhibitors. I’m curious what your thoughts are about checkpoint inhibitors, particularly triple-negative, but in breast cancer in general. And particularly the question that the docs have is, since the drugs are approved, are there situations where you’d want to give the drug outside a trial setting at this point, or do we need more data? DR SMITH: So the PD-1 inhibitors and the PD-L1 inhibitors are being used experimentally in metastatic breast cancer. And the results so far show that there are a small number of responses. DR SMITH: The main experience at present is with pembrolizumab, with PD-1 inhibitor. And the overall response rate there is fairly modest. It’s about 10% to 15%. But the point about these is that the responses, if you do achieve them, are sustained often for many months. So there’s clearly something in it if you can identify the appropriate patients. I think the most interesting data, although it’s rather small numbers, is with avelumab, where again — so PD-L1 inhibitor — where again, the overall response rate is low. It’s something like about 10%. But when they look specifically at what they call “hot spots” — that’s PD-L1-positive cells actually in the tumor — then the overall response rate goes up to about 33%. And when you look at the triple-negative who’ve got these hot spots, that goes up to 44%. However, the numbers are very small. But there’s encouragement there that if you can get the appropriate markers, then maybe this is going to be a very effective treatment. The other side of the coin, of course, patients love the idea of immunotherapy because, apart from anything else, they perceive it as being nontoxic. It’s anything but nontoxic. These drugs can have very severe and serious toxicities. And I think that’s a reason why I personally would not be using them outside a trial at present. And I think for the time being, they should only be used in units and centers that have got a lot of experience with the potential toxicities. DR LOVE: So another question Dr Astrow had, again in terms of the future therapy for this patient with metastatic triple-negative cancer, was the potential use of antiandrogens and doing an androgen receptor assay. Again, he raised the question, is this something that you would consider outside a trial setting? DR SMITH: The androgen receptor is an interesting thing in breast cancer. There’s actually a higher incidence of androgen receptor positivity across the board than there is of estrogen receptor positivity. And they’re very common in ER-positive cancers. In ER-negative, in triple-negative breast cancers, the incidence of androgen receptor positivity is a lot lower. It’s somewhere between about 15% to 25%. Enzalutamide is the drug that has been used most so far in Phase II trials with really disappointingly low response rates of around about almost single figures. I can’t remember. It certainly wasn’t more than about 10%. But again, there are some patients there who are responding. So the challenge is — as with all these other new drugs — is to define who are the patients who actually might benefit. I don’t have, personally, a great deal of experience with these drugs. I remember we used them many, many years ago, a whole different generation. They are associated with some degree of nausea. They’re not quite so well tolerated as the tamoxifen and the aromatase inhibitors. But the reason I raise that issue is they’re not hugely toxic. There’s not a lot of problems. And maybe as we use with endocrine therapy, if you’ve got androgen receptor positivity, you just try it. Suck it and see. So there’s something there, but at present it’s kind of disappointing. DR LOVE: So the third question or issue that Dr Astrow raised, again in triple-negative breast cancer — now, this woman did not have a BRCA germline mutation, but she did have triple-negative disease — was the issue of PARP inhibitors. And of course we’ve seen some really exciting data in ovarian cancer where these drugs are being used. What about, again, you get a patient with triple-negative disease. Maybe if they have a BRCA germline mutation even more so. Again, what do we know about PARP inhibitors in breast cancer? DR SMITH: Yes. You can almost lump the story of PARP inhibitors together with the story of carboplatin and cisplatin in breast cancer. There is no question both these approaches — let’s speak specifically about PARP inhibitors — are active when you have a BRCA mutation. And that’s well established. Theoretically, they ought to work when you’ve got homologous recombination dysfunction, when you’ve got HRD without a BRCA mutation, because that’s the underlying process. And they are effective in such patients in ovarian cancer. But the data so far suggest that they are not effective for these patients with deficiency of homologous recombination. But without a BRCA mutation, they don’t seem to work. And it’s disappointing they don’t, because you would imagine perhaps they would. And the same story is coming out for the role of carboplatin in triple-negative breast cancer. |