Clinical Question

Does anastrozole (Arimidex) decrease the rate of breast cancer in high-risk postmenopausal women?

Bottom Line

Postmenopausal women at high risk of developing breast cancer who take anastrozole for five years have a lower rate of developing invasive breast cancer during that time frame. (Level of Evidence = 1b)

Synopsis

These authors report outcomes from the second International Breast Cancer Intervention Study (IBIS-II), in which postmenopausal women in 18 countries who were at high risk of breast cancer were randomly assigned to receive anastrozole (1 mg daily for five years; n = 1,920) or placebo (n = 1,944). The authors used a complex series of definitions to identify high-risk women: 40 to 44 years of age with an estimated fourfold increased risk compared with the general population; 45 to 60 years of age with double the estimated risk; and 60 to 70 years of age with 1.5-fold increased risk. The authors also used the Tyrer-Cuzick model and included any additional women with an estimated 10-year risk greater than 5%. They excluded women who were premenopausal, had a previous breast cancer diagnosis, or had previously received chemoprophylaxis.

The researchers and support staff were masked to treatment allocation. The researchers evaluated the women at baseline, six months, 12 months, and then annually for five years. The researchers used intention-to-treat to analyze the rate of incident breast cancers. By the end of the study, 2% of women receiving anastrozole had invasive breast cancer compared with 3% of women who received placebo (number needed to treat = 62 for five years; 95% confidence interval, 38 to 155). Approximately one-third of the women in the anastrozole group and one-fourth in the placebo group stopped taking their medication, mainly because of side effects. There was no difference in the overall death rate (1%) in each group.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry plus government

Allocation: Uncertain

Setting: Population-based

Reference: CuzickJSestakIForbesJFet alIBIS-II investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial [published correction appears in Lancet. 2014;383(9922):1040]. Lancet.2014; 383 ( 9922): 1041– 1048.