CHEMOTHERAPY VERSUS ENDOCRINE THERAPY

There is a bias away from hormonal therapy in young women with visceral metastases, and I have a bit of a problem with that. In an asymptomatic patient presenting with pulmonary metastases — by definition, an incurable problem — our first obligation is to treat her condition without producing untoward toxicity. If she had symptomatic hepatic or pulmonary parenchymal metastases, maybe it would be a disservice to give her a trial of hormonal therapy. But, in a case like this, I think we owe the patient an 8- to 12-week trial of hormonal therapy to establish her ability to respond. The counter argument that hormonal therapies require too long to work, and that a patient like this doesn’t have 8 to 12 weeks to await the success or failure of a hormonal therapy is misguided. This patient clearly was able to benefit from what turned out to be a period of four-plus years from therapies that did her essentially no harm and gave her an excellent quality of life.

—Kevin Fox, MD

In this patient, I would start with two cycles of an anthracycline-based polychemotherapy regimen and re-evaluate. I would continue treatment until maximal response and then consider hormonal intervention. If she had a complete response and durable response to chemotherapy — which is unlikely — one might consider stopping all therapy and waiting for progression. When she has shown maximal benefit to polychemotherapy, I would definitely consider hormonal therapy.

In an ER/PR-positive patient, hormonal therapy is certainly something to be considered up front. A number of people — mostly in academic institutions — would espouse single-agent hormonal therapy or single-agent chemotherapy in an incurable asymptomatic individual with very valid reasons. This is perhaps a question of clinical bias, but I believe that in a young, otherwise healthy woman, you want to go for the biggest “bang for your buck” early on. If anthracycline-based combination chemotherapy has the highest response rates in metastatic disease, that’s where I would be starting.

The issue of patient age does sway clinicians into treatment, and some might say overtreatment. We tend to treat more aggressively in younger patients. I don’t know that all clinicians would treat her that way, but most clinicians in my circle, including my partners, and other local colleagues, would probably treat with polychemotherapy initially.

—Patricia Madej , MD

There are two major routes you can take. One is palliation — keep her feeling as good as possible for as long as possible. I would certainly use a chemotherapy that is easier in terms of side effects or think about hormonal blockade. The other approach is a more aggressive route including clinical trials with aggressive induction chemotherapy followed by higher doses of chemotherapy with stem cell support. Since we don’t know if there’s any advantage to the higher doses, you could go either way depending on the desires of the patient.

The choice really comes down to the kinds of risks patients want to take. We can do transplants safely, and the patients are usually back up to where they were before the transplant within a month or two after completing therapy. I find that the people who pursue this are usually young — 40 and less — tend to have limited stage IV disease as their initial diagnosis and are minimally pretreated. Many young patients with small children pursue this more aggressive option on the chance that they will have less disruption to their lives for a longer period of time. They know there is no guarantee.

We have two randomized trials of first-line high-dose therapy — the Philadelphia and Canadian trials. I tell patients that it appears that roughly nine months of maintenance chemotherapy is equivalent to a single high-dose cycle with stem cell support ^33-39.

In terms of the nontransplant option, depending on the number and size of the pulmonary nodules, you could certainly try hormonal therapy — either combined hormonal blockage with an aromatase inhibitor and goserelin or tamoxifen. If I were starting chemotherapy, I’d probably use capecitabine as my first choice.

—Linda Vahdat , MD

Hormonal therapy is underutilized in clinical practice for a variety of reasons. In my training days, we did adrenalectomies and hypophysectomies — major, fairly brutal surgical procedures with a lot of morbidity. At that time, the first aromatase inhibitor we had, aminoglutethimide, had a lot of side effects, and patients needed to take cortisone with it. Then we went on to megestrol acetate with its fluid retention and androgens, which women certainly don’t like taking. Now we have a much better group of agents with many fewer side effects, yet many oncologists remember hormonal therapy as something that they did before they had the access to chemotherapy. It is a mistake to skip hormonal therapy and go to chemotherapy, because you may never get a chance to come back to hormonal therapy. If you select your patients correctly, 60 to 70 percent will benefit from endocrine therapy — this is as good as anything we do in current medical oncology. This is palliation — keeping patients as comfortable and functional as possible for as long as possible. Patients presenting with symptomatic, rapidly progressive breast cancer need chemotherapy. But if you put them into some degree of remission, you may well be able to give them a chemo holiday and put them on one of the new hormonal agents and to maintain the remission for a fairly long period of time.

—Stephen Jones, MD

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