If you are at increased risk for developing breast cancer, four medications -- tamoxifen (Nolvadex®), raloxifene (Evista®), anastrozole (Arimidex®), and exemestane (Aromasin®) -- may help reduce your risk of developing this disease. These medications act only to reduce the risk of a specific type of breast cancer called estrogen receptor-positive breast cancer. This type of breast cancer accounts for about two-thirds of all breast cancers.

What is estrogen receptor-positive breast cancer?

Most breast cancer cells respond to hormones, specifically estrogen or progesterone. These hormones circulate in the blood. The cancer is called estrogen receptor positive if it responds to estrogen. This means that estrogen triggers the cancer to grow. Progesterone receptor-positive breast cancer means that progesterone triggers the cancer to grow.

How do tamoxifen, raloxifene, anastrozole, and exemestane reduce the risk of breast cancer?

Tamoxifen and raloxifene are in a class of drugs called selective estrogen receptor modulators (SERMs). These drugs work by blocking the effects of estrogen in breast tissue by attaching to estrogen receptors in breast cells. Because SERMs bind to receptors, estrogen is blocked from binding. Estrogen is the fuel that makes most breast cancer cells grow. Blocking estrogen prevents estrogen from triggering the development of estrogen-receptor-positive breast cancer.

Anastrozole and exemestane are in a class of drugs called aromatase inhibitors (AIs). These drugs work by blocking the production of estrogen. Aromatase inhibitors do this by blocking the activity of an enzyme called aromatase, which is needed to make estrogen.

How much do tamoxifen and raloxifene lower the risk of breast cancer?

Multiple studies have shown that both tamoxifen and raloxifene can reduce the risk of developing estrogen receptor-positive breast cancer in healthy postmenopausal women who are at high risk of developing the disease. Tamoxifen lowered the risk by 50 percent. Raloxifene lowered the risk by 38 percent. Overall, the combined results of these studies showed that taking tamoxifen or raloxifene daily for five years reduced the risk of developing breast cancer by at least one-third. In one trial directly comparing tamoxifen with raloxifene, raloxifene was found to be slightly less effective than tamoxifen for preventing breast cancer.

Both tamoxifen and raloxifene have been approved for use to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for use in both premenopausal women and postmenopausal women (women who have not had a period for one full year). Raloxifene is approved for use only in postmenopausal women.

What side effects have been seen with tamoxifen and raloxifene?

Less common but more serious side effects of tamoxifen and raloxifene include blood clots to the lungs or legs. Other serious side effects of tamoxifen are an increased risk for cataracts and endometrial cancers. Other common, less serious shared side effects of tamoxifen and raloxifene include hot flashes, night sweats, and vaginal dryness.

How much do anastrozole and exemestane lower the risk of breast cancer?

Studies have shown that both anastrozole and exemestane can lower the risk of breast cancer in postmenopausal women who are at increased risk of the disease.

In one large study, taking anastrozole for five years lowered the risk of developing estrogen receptor-positive breast cancer by 53 percent. In another study, taking exemestane for three years lowered the risk of developing estrogen receptor-positive breast cancer by 65 percent.

What side effects have been seen with anastrozole and exemestane?

The most common side effects seen with anastrazole and exemestane are joint pains, decreased bone density, and symptoms of menopause (such as hot flashes, night sweats, vaginal dryness).

How do I know which drug -- tamoxifen, raloxifene, anastrozole, or exemestane -- may be the best choice for me?

Because of the potential serious side effects of these drugs, experts at national cancer associations and organizations that examine preventive health care issues share the same advice: if you have a high risk of developing estrogen receptor-positive breast cancer, have an open and honest discussion with your doctor about the use of these drugs. Factors such as your age, race/ethnicity, personal medical history, family history of breast cancer, lifestyle factors (smoking, activity, alcohol use), your lifetime risk of breast cancer, and personal desires will determine if the benefits of taking any of these drugs outweigh the risks.

Key discussion points for you and your doctor include:

  • Translating statistics into useable information. Statistics can be tricky to understand. The statistic reported in the tamoxifen and raloxifene studies -- lowering the risk of developing breast cancer -- was a relative risk reduction. What this means to you depends on how high your risk is in the first place. For example, if your risk of developing breast cancer is 8 percent, reducing your risk by 50% would reduce your risk to about 4 percent. If your risk of developing breast cancer is lower to begin with, a 50% decrease in risk would be even smaller.
  • Choosing the best drug for my situation. An approach you and your doctor might consider is:
    • If you are premenopausal and are not at an increased risk for blood clots or uterine cancer, tamoxifen may be for you.
    • If you are postmenopausal and have osteopenia or osteoporosis and are not at an increased risk for blood clots, raloxifene may be for you. (Raloxifene is also approved to treat osteoporosis.)
    • If you are postmenopausal and have an increased risk for blood clots but no bone thinning issues, anastrozole, or exemestane might be the right choice for you.

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