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Chemoprevention of Breast Cancer

Doctors should not prescribe chemopreventive agents routinely for women who are at low risk for breast cancer, but they should discuss chemoprevention with women who are at higher risk.

The third U.S. Preventive Services Task Force (USPSTF) has been releasing new and updated guidelines during the past year (guidelines homepage; Journal Watch May 15 2001; Journal Watch Jun 4 2002).

USPSTF 3 concludes each of its guidelines with a recommendation, graded as follows:

A -- The intervention is strongly recommended.

B -- The intervention is recommended.

C -- The USPSTF makes no recommendation for or against the intervention.

D -- The intervention is not routinely recommended.

I -- Evidence is insufficient to recommend for or against the intervention.

Tamoxifen, when given as adjuvant therapy for breast cancer, reduces the risk for contralateral breast cancer. This observation led to the idea that tamoxifen might have value in primary prevention of breast cancer, and was the impetus for 3 randomized trials published in 1998. In a U.S. trial, prophylactic tamoxifen, given for nearly 5 years to high-risk women, reduced breast cancer risk by about 50%; however, findings from 2 European trials showed no reduction in breast cancer risk. In 1999, another group of U.S. investigators found that a second selective estrogen-receptor modulator, raloxifene, reduced breast cancer risk. There were strong trends toward more thromboembolic events in actively treated patients in all 4 studies, and tamoxifen was associated with an increased incidence of endometrial cancer in the U.S. trial. Only tamoxifen currently is approved for breast cancer chemoprevention in the U.S.

Analyzing this information, the USPSTF recommends against the routine use of tamoxifen or raloxifene for primary prevention of breast cancer in women at low or average risk for breast cancer. Recommendation: D

The task force recommends that clinicians discuss chemoprevention with women who are at high risk for breast cancer and at low risk for adverse effects from the drugs. Recommendation: B

Comment: The recommendation against chemoprevention for women at lower risk for breast cancer is straightforward: The potential harms of these drugs clearly outweigh the potential benefits. For high-risk women, the USPSTF found the benefit-harm ratio for drug therapy to be more favorable. The lack of drug benefit in the 2 European studies is concerning; the task force believes that the divergent results among the U.S. and European trials probably can be explained by several differences among the trials, including patient selection, statistical power, and duration of, and adherence to, therapy. The careful language of the USPSTF -- that clinicians should "discuss chemoprevention" and not simply recommend it -- reflects the complexity of the benefit-harm assessment and the important role of patient preferences. In an excellent accompanying editorial, the authors caution that the appropriate duration of therapy remains uncertain and that we still don't know whether chemoprevention actually saves lives. The full text of the original articles is available on the Agency for Healthcare Research and Quality website at http://www.ahrq.gov/clinic/uspstf/uspsbrpv.htm free of charge.

— Allan S. Brett, MD

Published in Journal Watch General Medicine July 19, 2002

Citation(s):

U.S. Preventive Services Task Force. Chemoprevention of breast cancer: Recommendations and rationale. Ann Intern Med 2002 Jul 2; 137:56-8.

• Original article (Subscription may be required)
• Medline abstract (Free)

Kinsinger LS et al. Chemoprevention of breast cancer: A summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002 Jul 2; 137:59-69.

• Original article (Subscription may be required)
• Medline abstract (Free)

Mulley AG Jr and Sepucha K. Making good decisions about breast cancer chemoprevention. Ann Intern Med 2002 Jul 2; 137:52-4.

• Original article (Subscription may be required)
• Medline abstract (Free)