DEFINING THE GOALS OF THERAPY

Whenever I have a patient with newly diagnosed metastatic disease, the first thing we talk about is not therapeutic options but goals for treatment. Patients deserve an understanding that this is not a disease that I can cure, so our goals are best focused on preserving the quality of their life while still hopefully extending survival. So giving them the most aggressive therapy with the most side effects just doesn’t make sense to me,unless that’s going to prolong the quantity or quality of their survival.

—Kathy M i l l e r, MD

Medical oncologists must remember that even if there is a therapy that causes an 80-percent response rate, the patient is not going to be cured. Metastatic breast cancer is a devastating disease and quality of life is a key issue. It is important to take your time and utilize the natural history of the disease. Some patients have very slow progression — some bone-only patients take years to become ill. It’s important to utilize that knowledge and have the poise not to jump in and treat patients with a new agent for every new lesion on a bone scan or every mild bump in tumor markers.

Our superb technology has now led to a new phenomenon in which many women with extensive prior therapies for metastatic breast cancer, who have a good performance status, are off therapy, and because of a new little something on the CT or an increase in a marker, they are looking for what to do.

—Hyman Muss, MD

ENDOCRINE THERAPY

I am a very strong believer in maximal use of hormonal therapy for women with hormone receptor-positive,metastatic breast cancer. In premenopausal women, I tend to use LH-RH agonists, often combined with tamoxifen. There is also interesting data now evolving on LH-RH agonists combined with aromatase inhibitors.26,27

—Joyce O’Shaughnessy, MD

I would rather have patients treated with hormonal therapies for as long as possible and delay the need to move to chemotherapy, because it has so many more side effects. I treat postmenopausal women with an aromatase inhibitor as their initial therapy and then with tamoxifen as a second-line therapy. They typically would then have a trial of megestrol acetate as third-line hormonal therapy, assuming disease progression is not rapid and they are not particularly symptomatic. And I still have some patients who are treated with fluoxymesterone.

Women who are still premenopausal at the time that their metastatic disease is identified usually have had adjuvant tamoxifen. What we typically do is start a gonadotropin agonist for ovarian ablation and switch them to a specific aromatase inhibitor. You could argue in favor of keeping the patient on tamoxifen and adding ovarian ablation, but it just makes more sense to me to switch them to an aromatase inhibitor, especially with the new comparison data suggesting that the aromatase inhibitors are probably a little bit better than tamoxifen.

—Kathy M i l l e r, MD

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TRASTUZUMAB

I’m fairly quick to get a FISH study if I see any whiff of even 1+HER2 positivity by immunohistochemistry — just to make sure that the woman isn’t HER2-positive. We use trastuzumab early in the course of metastatic breast cancer, because women with FISH-positive or 3+IHC overexpressing breast cancers do very well wih it. There is a debate about whether to give single-agent trastuzumab or combine it with a taxane, or some would say vinorelbine. For a woman with very limited asymptomatic disease — chest wall only, for example — I may choose single--agent trastuzumab.

—Joyce O’Shaughnessy, MD

We still see many patients whose tumors were not tested for HER2 when they were initially diagnosed, and all women with newly diagnosed metastatic disease should have their tumors tested even if the chance of overexpression seems quite unlikely, because there’s such a big difference with adding trastuzumab. For the rare subset of patients who are ER-positive and HER2 overexpressing, I still favor giving them a trial of hormonal therapy.

Their response rates are generally less than women who are ER-positive and HER2-negative, but the response rates certainly are not zero. And I still would prefer to delay intravenous therapy and chemotherapy for as long as possible unless they’re significantly symptomatic with rapidly progressive visceral disease.

—Kathy M i l l e r, MD

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