Related Pages Search for Clinical Trials 1 NCI's PDQ® Cancer Clinical Trials Registry. Breast Cancer Home Page 2 NCI's gateway for information about breast cancer. Study of Tamoxifen and Raloxifene (STAR) Trial 3 A collection of material about the Study of Tamoxifen and Raloxifene, or STAR trial, one of the largest-ever breast cancer prevention studies. The Breast Cancer Prevention Trial 4 A collection of material about the Breast Cancer Prevention Trial (BCPT).

Key Words: breast cancer, prevention, tamoxifen. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ⁵.)

Preliminary results from a large international trial, the International Breast Cancer Intervention Study (IBIS), provide additional evidence that the drug tamoxifen (Nolvadex®) can reduce the incidence of breast cancer in women at increased risk for the disease. Women taking tamoxifen experienced one third fewer breast cancers than women who took a placebo (dummy pill), researchers announced on March 20, 2002, at the 3rd European Breast Cancer Conference in Barcelona, Spain.

[Editor's note: These preliminary results were subsequently published in the Sept. 14, 2002, issue of The Lancet; see the journal abstract. Long-term results from the trial were later published in the Feb. 21, 2007, Journal of the National Cancer Institute; see the journal abstract.]

These findings are similar to those of the National Cancer Institute's Breast Cancer Prevention Trial (BCPT ⁴), a large U.S. study that in 1998 found a 49 percent reduction in new cases of breast cancer among participants who took tamoxifen for five years. Two other smaller European trials failed to find a lower incidence of breast cancer among women who took tamoxifen compared with those who took a placebo.

Although the new findings are encouraging, say IBIS researchers, they do not offer a conclusive answer to whether the benefits of tamoxifen outweigh the side effects in healthy women.

As in BCPT, IBIS found a two- to three-fold increase in risk for both endometrial cancer and serious blood clots among women who took tamoxifen. "Women who are at increased risk for breast cancer should talk with their doctors about the risks and benefits of taking tamoxifen," said Worta McCaskill-Stevens, M.D., of the Division of Cancer Prevention at the National Cancer Institute (NCI).

IBIS involves 7,000 healthy women in four European countries, Australia and New Zealand who have been randomly assigned to receive either tamoxifen or a placebo. Eligibility was determined by family history of the disease or a history of atypical hyperplasia, a benign (noncancerous) breast condition that is believed to increase risk for invasive disease, particularly in women with a family history of breast cancer.

The study found a similar reduction in breast cancer incidence regardless of age, risk level or use of hormone replacement therapy. (In the BCPT, participants were not permitted to use hormone replacement therapy.) However, in both trials, the reduction in incidence was seen only for breast cancers sensitive to the hormone estrogen.

In about seven out of 10 cases of breast cancer, the cancer cells have areas on their surface called receptors to which hormones such as estrogen and progesterone attach, providing fuel for the cells' growth into a tumor. Tamoxifen works by disrupting estrogen's ability to help cancer cells grow.

Participants in IBIS will continue to be followed to see if a particular high-risk group can be identified for whom the benefits of tamoxifen clearly outweigh the risks, said principal investigator Professor Jack Cuzick of Cancer Research UK, which is coordinating the study.

"Tamoxifen is a medically proven intervention, but it is not perfect. Women who are at an increased risk of breast cancer need options for preventing this disease with a minimum of side effects," said Leslie Ford, associate director for clinical research in NCI's Division of Cancer Prevention. "The NCI's Study of Tamoxifen and Raloxifene is a concerted effort to find such an option."

In the United States, the Study of Tamoxifen and Raloxifene (STAR ³) is now evaluating whether the osteoporosis prevention drug raloxifene (Evista®) reduces the risk of developing breast cancer as effectively as tamoxifen. STAR began in 1999 and will follow women for five to 10 years. Postmenopausal women who have an elevated risk of breast cancer are being recruited to participate in STAR; as of February 28, 2002, nearly 13,000 women had enrolled. A total of 22,000 women will be recruited, making STAR one of the largest breast cancer prevention studies ever conducted.

Unlike tamoxifen, raloxifene does not appear to increase the risk of endometrial cancer, said McCaskill-Stevens. "If raloxifene is shown to be as effective as tamoxifen at reducing breast cancer incidence, it would provide women at increased risk of breast cancer with a prevention option that has fewer side effects."

Like tamoxifen, however, raloxifene increases risk for blood clots. And because the safety of raloxifene in premenopausal women has not been established, enrollment in STAR is limited to women who have passed menopause.

Glossary Terms

Having to do with the endometrium (the layer of tissue that lines the uterus).

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

A cell protein that binds a specific hormone. The hormone receptor may be on the surface of the cell or inside the cell. Many changes take place in a cell after a hormone binds to its receptor.

Hormones (estrogen, progesterone, or both) given to women after menopause to replace the hormones no longer produced by the ovaries. Also called HRT and menopausal hormone therapy.

A type of hormone made by the body that plays a role in the menstrual cycle and pregnancy. Progesterone can also be made in the laboratory. It may be used as a type of birth control and to treat menstrual disorders, infertility, symptoms of menopause, and other conditions.

The active ingredient in a drug used to reduce the risk of invasive breast cancer in postmenopausal women who are at high risk of the disease or who have osteoporosis. It is also used to prevent and treat osteoporosis in postmenopausal women. It is also being studied in the prevention of breast cancer in certain premenopausal women and in the prevention and treatment of other conditions. Raloxifene blocks the effects of the hormone estrogen in the breast and increases the amount of calcium in bone. It is a type of selective estrogen receptor modulator (SERM).

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A drug used to treat certain types of breast cancer in women and men. It is also used to prevent breast cancer in women who have had ductal carcinoma in situ (abnormal cells in the ducts of the breast) and in women who are at a high risk of developing breast cancer. Tamoxifen is also being studied in the treatment of other types of cancer. It blocks the effects of the hormone estrogen in the breast. Tamoxifen is a type of antiestrogen. Also called tamoxifen citrate.