DR MORROW: This is a 51-year-old perimenopausal woman who presented with a 4-cm clinically node-negative breast cancer, or breast mass, that on core biopsy was a Grade III infiltrating ductal carcinoma, 80% ER-positive, 35% PR-positive and HER2-negative. She was complaining of some mild new-onset back pain, so she had a PET-CT scan, which showed uptake in the primary tumor in 1 axillary node and in the lumbar spine, which on the CT part of the scan was seen to be partially collapsed. This was biopsied and shown to be metastatic carcinoma.
She was put on tamoxifen and, after 12 months, was asymptomatic with no evidence of new metastatic disease. The SUV in all of her tumor sites had decreased substantially on the PET-CT scan. And her physical exam showed only a 2-cm, palpable breast mass. Would you recommend surgery at this point in time?
DR LOVE: We’ve been waiting to hear about this situation. It’s already come up in a couple of other cases. Can you give us a little bit more of a flavor about the woman herself and what she was thinking — what she was asking?
DR MORROW: The woman herself is an anxious, educated, somewhat high-powered New York person who —
DR HURVITZ: We don’t know anyone like that.
DR MORROW: — who feels impelled to examine her breasts on a weekly basis to ascertain whether or not the mass in the breast is changing in size and, therefore, requests frequent breast imaging studies to look at it and becomes angst-ridden over measurement differences of a millimeter or two on her imaging.
DR LOVE: Edith?
DR PEREZ: Easy. I would talk to you about doing surgery. In my experience, I’ve seen several cases of patients like this, in which there’s very good control of their systemic disease. And I usually see that the tumor grows in the breast first compared to the other side. So, based on my experience added to the clinical/psychological condition of this patient, I think that surgery would be a great approach.
DR LOVE: Just out of curiosity, how many people in your practice have you sent for primary surgery who had metastatic disease in the last year?
DR PEREZ: One. But we don’t see too many of those patients.
DR LOVE: I’m sure.
DR PEREZ: And there’s a trial ongoing that is accruing very, very poorly, unfortunately.
DR LOVE: Lisa, second opinion on this: What about surgery on the tumor and axilla in this lady with metastatic disease?
DR CAREY: The observational data support treating the primary tumor. The problem is that the observational data come from these kind of situations, where you would actually consider it in a patient who’s otherwise well, has oligometastatic disease, is healthy, et cetera. If the patient had a large tumor burden in the liver, who’s technically the same stage, you would never consider it. You, of course, influence prognosis that way.
That said, this is the kind of patient who seems to be doing better with an approach to local disease. I would probably treat her collapsed spine that’s giving her back pain with radiation, and then leave her on endocrine therapy NED afterward, if my surgeons were amenable.
DR LOVE: And just to tease it out a little bit more with both you, Lisa and Edith, suppose the met was in the lung or liver, as we were talking about before, rather than the bone. Would you take that out, too?
DR PEREZ: Yes.
DR CAREY: It depends on if it’s accessible or not. I mean, the liver is sometimes yes, sometimes no.
DR LOVE: But if accessible, would you do it?
DR CAREY: We’d consider it.
DR LOVE: Hope?
DR RUGO: I guess I have a question back because we do struggle with which of the patients to do surgery on or not. And I think we come to the same conclusions. I think we’d all consider surgery in this patient, in part because of her anxiety and in part because of what Edith mentioned, which is we do sometimes have more problem locally than distant in these patients. But then you end up in a situation where she had a clinically negative axilla, a node that was positive on PET after she had a biopsy — and I’m assuming fairly soon after a biopsy, so you can get inflammatory changes in the node — doesn’t have anything going on in her axilla now. So are you going to do a lumpectomy and sentinel node biopsy? Are you just going to go with a lumpectomy? Then can you really justify doing radiation therapy afterwards in this situation when you have incurable disease? I also agree with the management of the spine, if she has partial collapse. That’s my question back to you.
DR MORROW: I think if you make the commitment to operate it makes no sense to leave the axilla alone and leave potential disease there, even though we can’t clearly say, based on the observational and retrospective studies that exist, that biopsying or operating on the axilla provides added value, but the numbers there are pretty small. Doing a sentinel node biopsy is a 10-minute operation. Yes, if I were going to operate on her, I would do that.
I think the radiation question is a bigger one. In the ECOG protocol that Seema Khan is leading, that was mentioned, radiation is actually required. It is full therapeutic local treatments. And in the original paper that Seema and I did of 16,000 patients that opened the door to this question, we did actually find that there was a bigger benefit in patients with negative margins than positive margins, suggesting that the completeness of local therapy might be important.
The attitude that I take toward this, recognizing that we can’t get away from the selection bias, is: If you meet the general criteria of patients who have done well, meaning limited metastatic disease, some period without progression of disease and usually ER-positive or HER2-positive disease, because in our own data from Memorial when we looked at subsets, we couldn’t find any benefit in the triple-negative subset — just in patients with targeted therapy with their longer lives.
I offer it as an option to patients, being very clear to tell them we don’t know that it will improve their survival. On the other hand, patients are living longer. We have no idea what proportion of patients get into trouble on their chest wall from their biggest disease burden in this setting. And we also know that about 40% to 50% of patients in most of these studies were diagnosed with metastatic disease after surgery in the first place — low-volume metastatic disease that 10 years ago we never picked up because we didn’t have sensitive enough tests. So we were aggressively treating those patients with surgery, radiation and chemotherapy for cure.
I think the real tragedy here is none of us know the answer to this question and we have a clinical trial open that would actually provide the answer to this question that isn’t accruing.
DR LOVE: I don’t know if you were entering patients on that study, but it seems understandable that it not be accruing. It seems like a tough randomization.
DR MORROW: We are entering some patients into this study. But they primarily present to medical oncology and not to surgery. And there are concerns about the morbidity of the radiation, is the most common reason given for not referring patients to talk about the trial.
DR LOVE: Interesting. Adam?
DR BRUFSKY: I want to shift the case a little bit, just a touch. Say this lady had an A cup and say the tumor was 3 centimeters in diameter. She’s on tamoxifen, had a little bit of response. This being New York City, she needs a mastectomy, but she wants implant-based reconstruction with oligometastatic disease. Would you offer that to her?
DR MORROW: You mean as opposed to the ones who want contralateral prophylactic mastectomies —
DR BRUFSKY: Correct.
DR RUGO: Yeah.
DR MORROW: — at the same time, which I tell them I think is malpractice and refuse to do?
DR BRUFSKY: Right.
DR MORROW: I think that, again, this is a difficult thing. And it gets down to, yes, they’re unlikely to be cured of their disease, but they’re also likely to have a reasonable life span in the setting of ER-positive disease that’s responding to endocrine therapy. The morbidity of implant-based reconstruction is pretty low in terms of what is entailed surgically. So, yes, I would consider that. If somebody wanted to have, for example, a free flap where you’re talking about 8 or 9 hours in the operating room and 2 months of recovery, no.
DR LOVE: Lisa?
DR CAREY: These conversations, and we’ve had some similar ones over the course of the morning, are striking because the center of debate and the direction that we seem to be going in is increasing local therapy in the setting of primarily systemic disease. And what the CALOR study that was presented at San Antonio — increasing systemic intervention in what is essentially local disease — I think the point is: There may be, in fact, a greater role for multimodality and multidisciplinary therapy than, in fact, people had previously appreciated in this sort of siloed approach. And it seems to be cutting both ways.
DR BRUFSKY: I think biologically, not anatomically. I think that’s the way we need to start thinking.