Cuzick J, Sestak I, Forbes JF, et al; IBIS-II Investigators. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet. 2020;395;117-122.
EXPERT COMMENTARY
A manufacturer-sponsored trial initiated in 2003, IBIS-II (International Breast Cancer Intervention Study II) included 3,864 menopausal women (mean age at baseline, 59.4 years) at elevated risk for breast cancer. The women were randomly assigned to 5-year treatment with either placebo (N = 1,944) or the aromatase inhibitor anastrozole 1 mg daily (N = 1,920).1
Reporting on the long-term follow-up results of the trial, Cuzick and colleagues found that anastrozole use substantially reduced the incidence of all breast cancer, including invasive breast cancer and ductal carcinoma in situ. Key adverse events associated with anastrozole were fractures, arthralgias, and menopausal symptoms (vasomotor symptoms and vaginal dryness).
To determine whether anastrozole had any persistent impact, the investigators continued to follow participants for all breast cancers and other outcomes.2
Details of the study
This randomized controlled trial that included 3,864 postmenopausal women had a median overall follow-up of 131 months; the primary outcome was all breast cancer. Random assignment to anastrozole use (1,920 women) was associated with a 49% reduction in all breast cancer (85 cases vs 165 cases in the placebo group [N = 1,944]; HR, 0.51; 95% CI, 0.39–0.66; P<.0001).
In the first 5 years, risk reduction was 61% with anastrozole (P<.0001 for overall and the first 5 years of follow-up). Subsequently, the magnitude of the risk reduction attenuated to 37% (P = .014). With 12 years of follow-up, the estimated risk of being diagnosed with breast cancer was 8.8% and 5.3% in the placebo and anastrozole groups, respectively. The number needed to treat for 5 years to prevent 1 breast cancer was 29.
With anastrozole, prevention of estrogen–receptor positive tumors was substantially more robust at 54% (HR, 0.46; 95% CI, 0.33–0.65; P<.0001) than for estrogen–receptor negative tumors at 27% (HR, 0.77; 95% CI, 0.41–1.44; P = .41).
Over the course of the long-term study, the incidence of fractures and cardiovascular events was similar in the placebo and anastrozole groups. Arthralgias and menopausal symptoms were not assessed after the trial’s initial 5 years. Overall, the number of deaths (all cause as well as breast cancer related) were similar in the placebo and anastrozole groups.
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