Aromatase inhibitors

What are aromatase inhibitors?

Aromatase inhibitors are newer drugs that are sometimes used to treat breast cancer or help keep breast cancer from coming back after surgery. The drugs in this class include:

• Exemestane (Aromasin^®)
• Letrozole (Femara^®)
• Anastrozole (Arimidex^®)

Aromatase inhibitors work a little differently than tamoxifen and raloxifene. Instead of blocking the estrogen receptors, they stop a key enzyme (called aromatase) from changing other hormones into estrogen. This lowers estrogen levels in the body, taking away the fuel that estrogen receptor-positive breast cancers need to grow.

These drugs are only used in women who have already gone through menopause.

What are the benefits and risks of taking aromatase inhibitors?

Studies have shown that aromatase inhibitors are better than tamoxifen for treating advanced breast cancer. For keeping breast cancer from coming back after surgery, several studies have found that aromatase inhibitors (used instead of or after tamoxifen) are slightly better than tamoxifen alone.

Some short-term effects of aromatase inhibitors are much like those caused by tamoxifen and raloxifene, including hot flashes and vaginal dryness. Muscle and joint pain and headaches happen more often.

Aromatase inhibitors seem much less likely to cause serious blood clots.

Unlike tamoxifen and raloxifene, aromatase inhibitors tend to speed up osteoporosis (bone thinning), which can lead to broken bones.

Based on the studies done so far, they do not seem to raise the risk of endometrial cancer or uterine sarcoma, like tamoxifen and raloxifene do.

Because these drugs have been available for a shorter period of time, much less is known about other possible long-term effects they may have, such as on the risk of heart disease. Future research will help define these effects.

Are aromatase inhibitors approved for use in reducing breast cancer risk?

At this time, no, aromatase inhibitors are not approved to be used to reduce breast cancer risk. They are used either to treat advanced breast cancer or given after surgery (instead of or after tamoxifen) to help prevent breast cancer from coming back. The FDA has not approved any of these drugs to reduce the risk of developing breast cancer.

But one of these drugs has been shown to lower breast cancer risk in a clinical trial. The MAP3 study compared exemestane to placebo (sugar pill) in a large group of post-menopausal women who had an increased risk of breast cancer.

After an average of about 3 years on the study, there were 32 cases of invasive breast cancer in the women on placebo, while only 11 cases in the 2,285 women taking exemestane. This is a 65% lower risk in the exemestane group.

Exemestane did not have a strong effect on the risk of ductal carcinoma in situ, with 12 cases in the placebo group versus 9 in the exemestane group.

Most side effects were mild, with the most common side effects being hot flashes and joint pain. The women in the group treated with exemestane were not more likely to get osteoporosis or fractures (broken bones).

Other studies are looking at the effect of aromatase inhibitors on breast cancer risk. The British IBIS-II study is comparing anastrozole to placebo for 5 years in 6,000 post-menopausal women who are at increased risk of breast cancer. Results are expected in 2012. Smaller studies are also being done with letrozole.

Aromatase inhibitors to reduce breast cancer risk: More research is needed

Like raloxifene, aromatase inhibitors may some day prove to be as good as or even better than tamoxifen in reducing breast cancer risk, but more study results will be needed to show this. Much less is known about the possible long-term effects of these drugs. Even if they are shown to reduce risk, each woman and her doctor will still need to weigh the possible benefits and risks when deciding if one of them is right for her.