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Aromatase Inhibitors for Breast Cancer

Aromatase Inhibitors for Breast Cancer

Aromatase inhibitors are a type of medication that stops estrogen production in postmenopausal women.

Since aromatase inhibitors were introduced in the late 1990s, the FDA has approved three of them for treating breast cancer. They are:

  • Arimidex (anastrozole)

  • Aromasin (exemestane)

  • Femara (letrozole)

Currently, aromatase inhibitors are not approved for reducing the risk of developing breast cancer. 

What is hormone therapy?

Hormones are chemicals in the blood that control the growth and activity of normal, healthy cells. Certain hormones, however, such as estrogen, can also fuel the growth of some breast cancers.

Estrogen promotes the tumor growth in about two out of three breast cancers. Estrogen helps cancer cells grow by binding to a protein called an estrogen receptor, which is found in some breast cancer cells. (These are called estrogen-receptor positive [ER+] breast cancers.) When estrogen binds to this receptor, the cancer cells divide and the tumor grows.

A variety of hormone therapy drugs block estrogen's effect on breast cancer. They do this in several ways:

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

  • Tamoxifen and Fareston (toremifene) block estrogen from binding to its receptor.

  • Faslodex (fulvestrant) acts on the estrogen receptor by blocking estrogen from binding and by reducing the number of available estrogen receptors.  

Hormone therapies work only against tumors that grow in response to estrogen; that is, those that have estrogen receptors. An ER+ status shows that the tumor may respond to hormone therapy. All breast cancers should be tested for this when they are diagnosed. 

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. Cells in your muscles and fat, however, 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 called 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 ER+ 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, aromatase inhibitors are used only in women who have gone through menopause.

Aromatase inhibitors are not all the same. As listed above, there are three drugs that stop estrogen production by blocking the enzyme aromatase. All three are taken daily as pills.

An evolving role

For postmenopausal women who might respond to hormone therapy, most doctors now recommend using an aromatase inhibitor at some point during adjuvant therapy. Adjuvant therapy is treatment given in addition to the major treatment. Its purpose is to prevent or delay any remaining cancer cells from growing. However, several questions remain unanswered. It is not clear if starting adjuvant therapy with one of these drugs is preferable to giving tamoxifen and then switching to an aromatase inhibitor. It is also not clear how long to give tamoxifen or how long to give an aromatase inhibitor. Research is now being done to answer these questions.

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 you are most likely to experience:

  • Headache

  • Hot flashes

  • Mild nausea

  • Muscle and joint aches and pains and stiffness

  • 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.

Aromatase inhibitors rarely cause blood clots. However, they 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 bone 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.

 
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