DR. LOVE: To obtain another viewpoint on Dr Fox's case, I visited with Dr Patricia Madej, a community-based oncologist, and like Dr Fox she noted that patients presenting with metastatic breast cancer are unusual in clinical practice, but she differed in her approach to diagnosing the metastases in this situation.

DR. MADEJ: I don't think that that is a common presentation, but certainly, we would run into several situations a year, half a dozen or a dozen women, who will present initially with metastatic disease. The problem in this patient is the level of confidence that this is metastatic disease, because obviously, that makes a world of difference in how you're going to treat her and how she's going to plan out the rest of her life.

DR. LOVE: Would you recommend thoracotomy, thoracoscopy to get tissue?

DR. MADEJ: Yes, I would. Well, I think that in a patient such as you've described, the clinical picture is more than highly suggestive of metastatic disease. But the implications of metastatic disease in this individual are so overwhelming that I would feel that she definitely deserves the rule-out manner of thinking. And yes, I think if the patient were willing to, my initial recommendation would be for obtaining lung tissue.

DR. LOVE: Okay. Let's assume you do obtain lung tissue, confirms, and looks exactly like the breast cancer, ER-PR positive. Now let's talk about treating this woman, who's asymptomatic.
Let me break it down. I guess the first question is - I would think you're going to think about systemic therapy. What systemic therapy do you think you would use for a situation like this?

DR. MADEJ: I would start with an anthracycline-based therapy and probably AC or a FAC-type regimen and I would treat for two cycles and re-evaluate, and then continue treatment until maximal response, and then consider hormonal intervention.

DR. LOVE: So you're talking about starting chemotherapy and then, at some point, switching to hormonal therapy even without the tumor progressing, just kind of going from one to the other. Is that what you're thinking?

DR. MADEJ: If the patient were to have a complete response to chemotherapy, one might consider stopping all therapy and waiting for progression. But it is unlikely that she will have a complete and durable response to chemotherapy. So, most likely at the time that she has shown maximal benefit to polychemotherapy, I would definitely consider hormonal therapy in her.

DR. LOVE: Now, why not consider hormonal therapy up front?

DR. MADEJ: Certainly in someone who's ER-PR positive, it's something to be considered. And I am aware of a number of people - I have to say maybe mostly in academic institutions - who would espouse, with very valid reasons, single-agent hormonal therapy in an incurable asymptomatic individual, or even single-agent chemotherapy, for that matter; a single-agent taxane or anthracycline. But I believe that - and this is a question of, perhaps, clinical bias - in a young, otherwise healthy woman, you want to really go for the biggest bang for your buck early on. And if anthracycline-based combination chemotherapy has the highest response rates in metastatic disease, that's where I would be starting.

DR. LOVE: Do you think that you would see a higher response rate with chemotherapy than hormonal therapy in a patient like this?

DR. MADEJ: Yes, I do. I think one thing that does sway clinicians into treatment, and some might say over-treatment, perhaps, is the issue of the age of the patient. We have a tendency to treat more aggressively in the younger patient. I don't know that all clinicians would treat her that way, although most of the clinicians that I would be familiar with in my own circle would probably treat with polychemotherapy initially.

DR. LOVE: For example, your partners?

DR. MADEJ: My partners, other local colleagues. And I think that in the Chicago oncology community, my sense is that the majority of academicians would do so, as well. I think that, at least from what I hear at conferences, that would be the impression that I get. But when we refer patients to tertiary institutions, the recommendations haven't been that different.

DR. LOVE: That's interesting. I've heard that a lot from research leaders - that the response rate and overall benefit of hormonal therapy in a woman with metastatic breast cancer who's ER-positive are roughly the same as with chemotherapy. So why make the woman sick? The question of, well, yes, you have a younger woman, and the psychological issue of you want to give a strong medication, so to speak. But you're saying, maybe what people say in public and what they do when they see a patient is different, I guess.

DR. MADEJ: It may be. It may be. But I would also make the case that hormonal therapy isn't necessarily equated with not making somebody sick, especially when you're talking about a premenopausal woman. And the tolerance of a once-every-three-week dose of AC in some ways, for some individuals, is, in fact, superior to five years of joint aches, hot flashes, and some of the adverse effects of the anti-hormone therapy in a premenopausal woman.

DR. LOVE: But in this situation, for example, if you were going to use endocrine therapy - and you mentioned you might use it after chemotherapy - what hormonal intervention would usually be your first line in a premenopausal woman with metastatic disease?

DR. MADEJ: It would be tamoxifen.

DR. LOVE: Now, what about this history of the siblings with pulmonary emboli? Would that turn you off a little bit?

DR. MADEJ: It would give me pause. It would definitely give me pause. And you had said that her coagulation workup was negative -

DR. LOVE: Right.

DR. MADEJ: -- and, I assume that we're specifying the full gamut of hyper-coagulability tests - including prothrombin mutation and factor V Leiden - that can't be found as a predisposing factor. If the patient were, indeed, to have any of those, I would have some pause at giving tamoxifen. The family history raises a red flag, but, in my opinion, in a woman with this level of disease, would not necessarily contraindicate anti-estrogen therapy for her.

DR. LOVE: Well, let me tell you what happened to this woman, actually, at this point. And then we'll say what you would do. Let's say that the patient was treated in the manner I'm going to describe. And then she comes to you for treatment.

DR. MADEJ: Okay.

DR. LOVE: In fact, the treatment she got was the LH-RH agonist, Zoladex. No chemotherapy, just the Zoladex. And she had a good partial response in both the breast and the lungs, and it lasted about 28 months. At which point, while on the Zoladex, the lesions started to grow. So, she continues to be asymptomatic. So, at that point she moves to your area, she walks in, she's on Zoladex, but now she's progressing. At that point, what do you think you would do?

DR. MADEJ: In this particular scenario, I would consider some other hormonal intervention at that point in time. She's clearly shown a response clinically, and it has been one of a significant duration of time, so that another hormonal intervention could be considered.

DR. LOVE: Such as?

DR. MADEJ: Probably at this point in time, our next step would be to look at the aromatase inhibitors in this lady.

DR. LOVE: Now, we don't really know much about aromatase inhibitors in premenopausal women. However, this woman actually has been made menopausal. So, would you just look at her and say, "Well, yeah. She's still maybe a young woman, but she's functionally a postmenopausal woman," and keep her on the LH-RH agonist and add in an aromatase inhibitor?

DR. MADEJ: Yes. I think that would be the first way I would go with her.

DR. LOVE: What's been your experience with the new aromatase inhibitors?

DR. MADEJ: Well tolerated. There certainly is measurable efficacy in hormone-receptor patients, who have, as second-line and as third- line.

DR. LOVE: Is there one in particular that you're using now, or do you use all three, or how do you sort of use them?

DR. MADEJ: I don't know that we have a very good paradigm as to which aromatase inhibitor to use first-line or second-line. Certainly, we've used Arimidex as our first-line aromatase inhibitor since it's come out. With the data that we're getting on some of the Femara versus tamoxifen studies, I've been probably using that drug equally, if not more, as a second-line hormonal treatment.

DR. LOVE: How do you sort of process what you've heard about Arimidex and Femara? Do they seem the same to you? How do you sort of differentiate?

DR. MADEJ: I don't perceive much of a difference.

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