Dr. Susan Love Research Foundation | Breast Cancer Prevention Study Launches in the US, Canada

A new breast cancer prevention trial is now getting underway in the United States and Canada. The trial, called ExCel, is the first in North America to evaluate whether an aromatase inhibitor can reduce breast cancer risk. Similar trials have already begun in Europe.

Aromatase inhibitors are a type of hormonal therapy. Hormonal therapies slow or stop breast cancer's growth by changing the hormonal milieu. Aromatase inhibitors are currently approved for use to treat women with early stage and metastatic breast cancer. The ExCel study will evaluate whether the aromatase inhibitor exemestane (brand name Aromasin) can reduce breast cancer risk in women at high risk for the disease.

Aromatase inhibitors block an enzyme called aromatase that plays a key role in the body's creation of estrogen. In premenopausal women, most estrogen is made in the ovaries. In contrast, in postmenopausal women, most estrogen is made locally in different organs (bone, breast, brain, fat, and muscle). The ovaries and adrenal glands produce the hormones testosterone and androstenedione. The aromatase enzyme converts these hormones into estrogen. Aromatase inhibitors block this enzyme throughout the body, which stops testosterone and androstenedione from becoming estrogen.

Only postmenopausal women whose tumors are hormone-positive (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive) can use an aromatase inhibitor. You can read more about aromatase inhibitors here.

Hormonal therapies are used to treat both early stage breast cancer and cancer that has metastasized. For nearly two decades, tamoxifen has been the primary adjuvant (postsurgical) hormonal treatment for breast cancer. But new data comparing an aromatase inhibitor to tamoxifen in postmenopausal women has shown that the aromatase inhibitor works better. As a result, these drugs have become more widely used. The latest recommendation, released by the American Society of Clinical Oncology in November 2004, suggests that most postmenopausal women use an aromatase inhibitor as adjuvant hormonal therapy.

Tamoxifen and raloxifene are currently the only FDA-approved drug for breast cancer risk reduction. You can read more about using tamoxifen or raloxifene for breast cancer prevention here.

Scientists believe that the aromatase inhibitors may be even better than tamoxifen at reducing breast cancer risk in postmenopausal women. But we don't yet know what the benefits or the side effects will be, which is why trials like ExCel are getting underway.

ExCel will enroll 4,500 postmenopausal women in the United States, Canada, and Spain who are at high risk for breast cancer. Women will be randomized to receive either exemestane or a placebo for five years. After the trial is completed, researchers will look at how many women in each group developed breast cancer and use that information to determine how effective exemestane was at reducing breast cancer risk.

You can learn more about the ExCel study online or by calling 1-800-4-CANCER (in the US) or 1-888-939-3333 (in Canada).

Susan says:
Breast cancer prevention with tamoxifen, raloxifene, or an aromatase inhibitor is based on the theory that blocking estrogen, which stimulates breast cancer growth, will keep breast cancer from occurring.

Taking a drug to reduce breast cancer risk sounds like a good thing. But it's not that easy.

Tamoxifen has been approved for breast cancer risk reduction for high-risk premenopausal and postmenopausal women. Raloxifene is only approved for use by high-risk postmenopausal women. Only high-risk postmenopausal can enroll in the Excel study. Only women who are considered high risk for breast cancer can take tamoxifen for breast cancer reduction. And only women who are high risk will be able to enroll in the ExCel study. (Women are considered high risk if they have a Gail risk score of at least 1.66, have been diagnosed with DCIS or LCIS or have been found to carry a BRCA mutation.) What's wrong with this? We're actually not all that good at determining who is high risk. In fact, most women who get breast cancer don't have any known risk factors. And even if you are considered to be high risk, it doesn't mean you will get breast cancer. There is also the issue of side effects. In the case of tamoxifen, these side effects include an increased risk for uterine cancer and blood clots. With the other aromatase inhibitors, these side effects include a higher risk of fractures and bone and joint pain. These side effects may be worth the cost of treatment if you already have breast cancer. But to be exposed to these side effects when you are healthy—and may never get breast cancer—may not be.

Studies have found that many women who are considered high risk for breast cancer are not interested in taking tamoxifen because of the side effects. Whether these women would be more interested in taking an aromatase inhibitor if these drugs are found to be effective in the risk reduction setting remains to be seen. If you are postmenopausal and believe you are at high risk for breast cancer and are interested in the ExCel study, you should meet with a breast cancer specialist to discuss your risk factors for the disease, all your risk reduction options, and the risks and benefits of exemestane.