SELECTING PATIENTS FOR ENDOCRINE THERAPY

With rare exceptions, I consider hormonal therapy only for ER/PR- positive patients. We know that patients whose tumors are truly ER-and PR-poor have very little chance of deriving a clinical benefit from hormone therapy. However,there is the occasional patient who has a breast biopsy from many years earlier labeled ER/PR-negative, yet their clinical history is entirely consistent with hormone-responsive disease. In that rare patient, I would consider hormone therapy despite an old report of receptor negativity.

I would think about using hormone therapy in patients with very low levels of receptors, of course mixing the clinical presentation into the decision. In a patient with a low degree of receptor positivity, a long disease-free interval, bone-only metastases and modest symptoms, I’m going to treat with hormones. In a patient with a low degree of receptor positivity in visceral crisis, I’m going to use chemotherapy, although I may consider hormone therapy once they ’ve achieved maximal benefit from chemotherapy.

—Clifford Hudis, MD

PATIENT ASSESSMENT IN THE METASTATIC SETTING

When I approach patients with metastatic breast cancer, my first concern is palliation. By that, I mean treatment of the current symptoms as well as prevention of reasonably foreseeable symptoms.The first question I always ask is, “What ’s bothering you the most?” My first job is to do something about that, and then I go on to secondary things. My primary thought always is: “How am I going to make this patient’s life better or at least prevent it from getting worse?”

This, of course,immediately leads to the question of how to approach these patients in terms of treatment. Philosophically, I always want to use hormone therapy first. Only when I think hormone therapy no longer offers potential benefit do I move on to systemic chemotherapy or drugs like Herceptin. Of course,clinical trials are always an option at any stage.

—Clifford Hudis, MD

ENDOCRINE THERAPY PLUS TRASTUZUMAB

Combinations of trastuzumab and endocrine therapy need to be looked at in clinical trials of hormone receptor-positive, HER2- positive patients. We’re participating in a pilot study just to make sure it is safe. The important thing about these kinds of trials is that the comparison shouldn’t just be combination versus single agent, but rather combination versus sequential therapy. The issue is going to be, “I have used one of the drugs, and I can move to the other in the event of progression.” Ultimately we’re going to have to look at these therapies in sequence. Is there really an advantage to using the two agents together? Is there some type of synergy, for example, that would give the patient an advantage over use in a sequential fashion?

—Debu Tripathy, MD

TRASTUZUMAB WITH OR WITHOUT CHEMOTHERAPY

Trastuzumab is clearly one of the major triumphs of the last few years. It’s exciting on many levels, largely, of course, because of the clinical benefit, but also because of the way it opens up a new era of integrating science into the clinic. My approach is to identify the HER2 status on all of my patients with metastatic disease. For patients who are HER2-positive — and by that I mean 3+ by IHC using Hercept test or FISH-positive — I’m always thinking about the use of trastuzumab.I use it when hormone therapy is no longer an option. At that point, I would use it either alone in the patient with relatively indolent disease or in combination with chemotherapy in the patient who clearly needs chemotherapy.

Right now, I wish we had randomized data on the question of trastuzumab plus or minus chemotherapy. We don’t. What we clearly have are data on trastuzumab as first-line therapy from a study that Chuck Vogel reported, and we have data on chemotherapy plus or minus trastuzumab. Discriminating between these two settings is somewhat challenging. That said, my approach is to look at patients with Stage 4 disease and ask myself, “Do they need chemotherapy based on their presentation?” If the answer is yes and they’re HER2-positive, then I use chemo-trastuzumab. If the answer is no, maybe they don’t need chemotherapy right now, but if I ’m out of hormone therapy options, I might use trastuzumab as a single agent.

—Clifford Hudis, MD

CHOICE OF ENDOCRINE THERAPY

In the past, I was reluctant to use aromatase inhibitors first-line. But now we have more data. There is an accumulating body of evidence that the aromatase inhibitors may have some superiority to tamoxifen. I’m talking to patients now about starting on letrozole or anastrozole. In Canada we’re on the cusp of making that flip, but from what I’m hearing, in the United States most people have moved to aromatase inhibitors first-line.

We’ve been involved in a trial in Canada comparing exemestane to tamoxifen. But it’s been my question since we started talking about the trial, whether everyone will flip to using one of the aromatase inhibitors in first-line and whether this trial may be outdated or outmoded and not be able to be done.

—Kathleen Pritchard, MD

CHOICE OR AROMATASE INHIBITOR

My read would be that so far as we can see, all three of the aromatase inhibitors are probably pretty similar. I’ve not seen something convincing to distinguish them. We’re using both anastrozole and letrozole. I wouldn’t particularly differentiate. Sometimes patients come in, having read about one or another and have a preference, and I just go with it.

The curves for the first-line studies of anastrozole versus tamoxifen and letrozole versus tamoxifen separate early in terms of responses and progression-free survival. At the end of three months, there’s quite a difference between both tamoxifen and anastrozole and tamoxifen and letrozole.The separation is at the same place, as though there’s a group of women who are responsive to each of these aromatase inhibitors who aren’t responsive to tamoxifen. In both these studies, we’re seeing a similar phenomenon.

—Kathleen Pritchard, MD

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