Hormonal Therapy for Breast Cancer: New Options

imported_womens-health · 05-13-2006 03:32 PM

Hormonal Therapy for Breast Cancer: New Options

By: Paul Goss, MD, PhD, FRCPC, FRCP
By: Stephen E. Jones, MD
This year, approximately 200,000 women will be diagnosed with breast cancer in the United States. In all likelihood, the news will come as a rude and frightening surprise, and these women will be faced with a series of decisions they hoped they?d never have to make.
The good news waiting for them is that breast cancer treatment options are increasingly effective, and increasingly plentiful. Many people are already familiar with radiation and chemotherapy but for many women, hormonal therapy will be the best option for slowing, or even stopping the growth of cancer cells.

Below, two breast cancer experts offer an overview about how hormonal therapies are being used for breast cancer.

What do hormones have to do with the development of breast cancer?
PAUL E. GOSS, MD: In certain types of breast cancer that are estrogen receptor-positive, the hormone estrogen can promote breast cancer growth.

What does hormone therapy do?
STEPHEN E. JONES, MD: One use of hormone therapy is to control or stop the growth of cancer in patients with recurrent breast cancer. Now we can also use hormonal treatments to both prevent breast cancer in those who are at very high risk of developing it, in addition to preventing cancer recurrence.

What is the standard hormonal treatment currently being used?
STEPHEN E. JONES, MD: There are a lot of different treatment options, but the gold standard for twenty-five years has been a drug called tamoxifen. However, there is a whole group of newer drugs that look, in some ways, like they might be better than tamoxifen.

And how does tamoxifen work?
STEPHEN E. JONES, MD: Tamoxifen is in a class of drugs called "antiestrogens". It binds to hormone receptor cells within breast cancer cells and stops the cells from dividing.

How are the new hormonal therapies that are coming out different from tamoxifen?
PAUL E. GOSS, MD: The new drugs are called anti-aromatase agents. This is how they work: Estrogen is normally produced by the ovaries, but in post-menopausal women, most of the estrogen is produced from certain cells like fat and liver cells. In these cells, an aromatase enzyme helps convert male hormones called androgens into estrogen. If you block the enzyme, or you "antagonize" it with the so-called anti-aromatase drugs, the enzyme cannot promote estrogen production.

STEPHEN E. JONES, MD: Essentially, they shut down estrogen production in the body.

How are these new agents been used differently from tamoxifen?
STEPHEN E. JONES, MD: We?ve used them first in advanced metastatic recurrent breast cancer. As they?ve shown success there, we?ve moved them earlier and earlier into the treatment scheme. They have all now been compared to tamoxifen as first-line treatment for patients with recurrent breast cancer. And, in fact, in that setting they all appear to be better than tamoxifen.
The next logical step is to move them into early breast cancer, the adjuvant setting, to reduce recurrence of disease. Those studies are under way, and a lot of attention?s been focused on them.

How are they proving more effective than tamoxifen?
PAUL E. GOSS, MD: Tamoxifen has a 5-year benefit during treatment and a 15-year ?hangover effect? we call it, which means that its good effects last that long. So tamoxifen?s a fabulous life-insurance policy that lasts about 20 years.

We?re looking to improve that 20-year survival profile with the anti-aromatase agents. Given at the very beginning, and given perhaps for longer, we hope to make the 20-year survival much better. The results of the first trial, after just five years, which is comparing anastrozole [anti-aromatase agent] to tamoxifen has been reported. Sure enough, it beats tamoxifen considerably.

And how will anti-aromatase agents be used in breast cancer prevention?
PAUL E. GOSS, MD: Breast cancer doesn?t come about overnight. You?re not well one day and the next day you have cancer. That?s not what happens. It takes years and years for the normal, healthy epithelial cells to convert into cancer. So there are many precursor lesions, or preinvasive tumors, that women have in their breasts that can be precursors of cancer. And we?ve learned how to identify some of them.

Tamoxifen and now the anti-aromatase agents are easy to tolerate. They are once-a-day pills. They?re analogous to taking a blood-pressure pill or a cholesterol pill. In the last ten years, we?ve moved them from the treatment setting -- once a woman has identified cancer -- to a pre-treatment setting, where you have an identified risk of cancer, but you haven?t actually got cancer. So we?re now using tamoxifen in women at high risk of breast cancer.

A landmark trial of 13,500 patients that was done in the United States and Canada showed a 50% reduction in breast cancer occurrence in women exposed to tamoxifen at above 35 years of age.

What are the side effects of the anti-aromatase agents compared to tamoxifen?
STEPHEN E. JONES, MD: In general, the side effects of hormonal therapy are much milder than they would be, for example, with chemotherapy. So that?s the first really important message.
Some of these anti-aromatase agents appear to have fewer side effects than tamoxifen. There?s a drug called "exemestane" -- -- which may have significantly fewer hot flashes than tamoxifen.

We think all these drugs are going to produce less risk of things like blood clots and probably less risk of uterine cancer, which is one of the potential complications of tamoxifen therapy.

PAUL E. GOSS, MD: The anti-aromatase agents have no potential really serious side effects. This class of agents is extremely well-tolerated. Women can take these drugs with fewer side effects than a cholesterol-lowering drug. And actually, we can divide them into two subsets, there?s the so-called "nonsteroidal." and the "steroidal" agents. The nonsteroidals just remove estrogen, so they cause some of the same problems that menopause causes, like hot flashes and urogenital aggravation. There also could potentially cause osteoporosis and lipid-metabolism abnormalities.

The steroidal agents do the same thing in one way -- knock down estrogen. But because of its steroidal structure, it could actually protect the bone and lipid levels.

With all the new developments, what advice do you have for cancer patients?
PAUL E. GOSS, MD: Breast cancer patients need to understand the term "aromatase inhibitor" or "anti-aromatase agents" and they need to understand that there are three new drugs available. The public knows about tamoxifen, but they don?t really know about this class of drugs, and they need to discuss these options with their doctor.

STEPHEN E. JONES, MD: It?s not yet time to give up tamoxifen as the gold standard. And we have to keep things in perspective. We?ve used tamoxifen now for 25 years, and hundreds of thousands of women?s lives have been saved. It?s too soon to abandon it as the major hormonal strategy.

But I think these new anti-aromatase agents have the potential -- down the road, in the next two to five years -- of replacing tamoxifen, if the current studies are completed and the results are as good as we expect they will be.

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**yanochuks** · 12-14-2006 07:42 AM

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