Aromatase Inhibitors for Breast Cancer

Aromatase inhibitors are a new type of hormone therapy used to treat breast cancer. These agents are effective in treating breast tumors that are stimulated to grow by the hormone estrogen. They are recommended for women who have gone through menopause.

Since aromatase inhibitors were introduced in the late 1990s, the U.S. Food and Drug Administration (FDA) has approved 3 of them for treating breast cancer. They are:

• Arimidex (anastrozole)

• Aromasin (exemestane)

• Femara (letrozole)

What Is Hormone Therapy?

Hormones are chemicals in the bloodstream that control the growth and activity of normal, healthy cells. But certain hormones, such as estrogen, can also fuel the growth of some tumors, including breast cancer.

About two-thirds of breast cancers are sensitive to estrogen. This means that estrogen’s presence causes the tumor to grow. Estrogen promotes tumor growth by binding to a protein called an estrogen receptor, which is found in some breast cancer cells. When estrogen binds to this receptor, the cancer cells divide and the tumor grows.

A variety of hormone therapies block estrogen’s effect on breast cancer. They do this in several ways.

• Aromatase inhibitors reduce the amount of estrogen in the body.

• Nolvadex (tamoxifen) blocks estrogen from binding to its receptor.

Tamoxifen is currently the hormone therapy most commonly used for estrogen-sensitive breast cancers. It is recommended in premenopausal women diagnosed with estrogen-receptor positive (ER+) breast cancer.

Hormone therapies work only against tumors that grow in response to estrogen--that is, those that carry estrogen receptors. An ER+ status shows that the tumor may respond to hormone therapy.

How Aromatase Inhibitors Work

If you have not yet gone through menopause, your ovaries still produce most of the estrogen in your body. After menopause, your ovaries no longer make large amounts of estrogen. But your muscles and fat still produce some estrogen from male hormones called androgens.

Aromatase inhibitors work by blocking the production of estrogen from androgens. These drugs interfere with the enzyme aromatase. Its role is to convert androgens, such as testosterone, into estrogen. By interfering with estrogen production, aromatase inhibitors deplete the body of estrogen. This helps slow or stop the growth of breast tumors, sometimes even shrinking them. Researchers have found that the drugs cannot lower estrogen levels enough to affect tumor growth in younger women. That’s because their ovaries still make high levels of estrogen. For this reason, these drugs are used only in women who have gone through menopause.

Aromatase inhibitors are not all the same. Two major classes of these drugs work in slightly different ways. Type-1 inhibitors include exemestane, which has a lasting effect on estrogen production. Once a woman takes it, she will not be able to make estrogen again. Type-2 inhibitors include anastrozole and letrozole. They work only while you are taking the drug. Once the drug is stopped, your body can make estrogen again. All 3 drugs are in pill form.

An Evolving Role

For the last 20 years, tamoxifen has proven to be a powerful drug for treating and preventing breast cancer in many women. But it is not without its problems. Though rare, blood clots and uterine or endometrial cancer can arise as a result of taking tamoxifen. Evidence is showing that aromatase inhibitors are effective and safe alternatives to tamoxifen in many postmenopausal women who have ER+ breast cancers.¹

Currently anastrozole and letrozole are used to treat breast cancer in postmenopausal women who have advanced or metastatic breast cancer (cancer that has spread beyond the breast). You may use these drugs before other hormone therapies are prescribed or after another hormone therapy, such as tamoxifen, has stopped working. Postmenopausal women can use exemestane if they are no longer benefiting from tamoxifen.

The FDA has approved anastrozole for use after surgery in women with early-stage breast cancer. This extra treatment is called adjuvant therapy. Its purpose is to prevent or delay any remaining cancer cells from growing.

Recently, a study of early-stage breast cancer survivors showed that adding letrozole to the drug regimen reduces the chance that breast cancer will recur or come back. Postmenopausal women who took letrozole after completing 5 years of tamoxifen therapy were less likely to have their cancer return than women not taking letrozole.²

Researchers are also interested in finding out if aromatase inhibitors can prevent breast cancer in postmenopausal women who are at high risk for the disease. More research is needed to see if these drugs can fill this role.

Side Effects and Risks

In general, aromatase inhibitors do not cause serious short-term side effects. These are the most common side effects. They’re listed in alphabetical order. Ask your doctor which ones are most likely for you.

• Headache

• Hot flashes

• Mild nausea

• Muscle and joint aches and pains

• Stomach upset

• Vaginal dryness

These are usually mild. If you do have side effects, you’re more likely to have them in the first few weeks. Only in rare instances do side effects require that the treatment be stopped.

In the long term, aromatase inhibitors are less likely to cause endometrial cancer or blood clots than tamoxifen. However, these drugs do increase the risk for bone thinning, which can develop from a lack of estrogen. This can make bones more brittle and likely to break. Talk with your doctor about what you can do to prevent or manage these problems, such as exercising and taking calcium. Drugs called bisphosphonates can prevent or reverse bone loss.  Talk with your doctor about whether you need them.

Because estrogen has healthful effects on the heart and on brain function, researchers are looking into the effects these drugs may have on these organs. Ongoing research will more clearly determine the long-term risks and benefits associated with the use of aromatase inhibitors.