Chemoprevention Only for High-Risk Women

August 1, 2002

ROCKVILLE, Maryland-The US Preventive Services Task Force (USPSTF) has recommended against the use of tamoxifen (Nolvadex) and raloxifene (Evista) for the primary prevention of breast cancer in women at low or moderate risk

ROCKVILLE, Maryland—The US Preventive Services Task Force (USPSTF) has recommended against the use of tamoxifen (Nolvadex) and raloxifene (Evista) for the primary prevention of breast cancer in women at low or moderate risk of the disease. Tamoxifen is currently approved for use as chemoprevention in high-risk women. The panel urged physicians to fully discuss chemoprevention with their high-risk patients and inform them of the risks and benefits of using the drugs.

"The task force found fair evidence that tamoxifen can significantly reduce the risk of invasive estrogen-receptor-positive breast cancer by approximately 50% in women at high risk of the disease," said Janet Allan, PhD, RN, the group’s vice chair. "We found consistent evidence for raloxifene, but it was limited to one study that focused on the use of the drug to prevent fractures."

USPSTF is an independent group of experts sponsored by the Agency for Health Care Research and Quality (AHRQ) that makes recommendations across the prevention spectrum. It based its recommendations on a review led by Linda Kinsinger, MD, and Russell Harris, MD, of AHRQ’s Evidence-based Practice Center at RTI International-University of North Carolina.

Tamoxifen is the only drug FDA approved for breast cancer risk reduction. However, some research suggests that raloxifene may also reduce a woman’s risk of the disease. Raloxifene is FDA approved for the prevention and treatment of osteoporosis, and some clinicians prescribe it off-label for breast cancer risk reduction.

The STAR Trial

Currently, researchers are accruing 22,000 postmenopausal women age 35 or older who are at increased risk of breast cancer for the Study of Tamoxifen and Raloxifene (STAR). This ongoing trial, supported by the National Cancer Institute, is designed to compare the safety and efficacy of the two drugs. In the first 3 years of the study, researchers at more than 500 sites in the United States, Puerto Rico, and Canada enrolled 13,647 women. Enrollment is scheduled to continue through June 2004.

The task force based its recommendation against use of the two drugs for chemoprevention in low- and moderate-risk women on the potential for harmful side effects that might not outweigh their benefit in reducing breast cancer. These adverse effects include hot flashes and an increased risk of blood clots in the legs and lungs. Tamoxifen also increases a woman’s risk of endometrial cancer.

The report noted that the estimated benefits of tamoxifen vary, depending on a number of factors, particularly a woman’s age, her family history of breast cancer, and a history of atypical hyperplasia on breast biopsy. A woman’s risk of developing breast cancer in the next 5 years can be assessed with the NCI’s Breast Cancer Risk Tool, often called the Gail model.

"Clinicians can use this information to help individual patients considering tamoxifen therapy estimate the potential benefit," the report said. "However, the validity, feasibility, and impact of using the Gail model to identify appropriate candidates for chemoprevention have not been tested in a primary care setting. The Gail model does not incorporate estradiol levels or estrogen use, factors that some studies suggest may influence the effectiveness of tamoxifen."