Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND

Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low.

PURPOSE

To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer.

DATA SOURCES

MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists.

STUDY SELECTION

English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment.

DATA EXTRACTION

Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria.

DATA SYNTHESIS

Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer.

LIMITATION

Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking.

CONCLUSION

Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates.

PRIMARY FUNDING SOURCE

Agency for Healthcare Research and Quality.