The updated analysis of the IBIS-II trial showed that breast cancer incidence among postmenopausal women who are at high risk of developing the disease continued to be significantly reduced 5.9 years after stopping a 5-year treatment period with the aromatase inhibitor (AI) anastrozole. These results indicate a long-term preventive benefit with anastrozole for oestrogen receptor (ER)-positive breast cancer in postmenopausal women.
IBIS-II Prevention was designed to investigate whether 5 years of anastrozole can safely and effectively prevent breast cancer in postmenopausal women who are at high risk for developing the disease . This was the case if these women fulfilled any one of a number of criteria, such as having 2 or more blood relatives with breast cancer, having a mother or sister who developed breast cancer at an age <50, or having a mother or sister who had breast cancer in both breasts. The primary objective of this study was to determine the efficacy of anastrozole in preventing breast cancer (both invasive and ductal carcinoma in situ [DCIS]), overall and particularly for the post 5-year time period. Primary endpoint of the study was breast cancer incidence (both invasive and DCIS). Secondary endpoints were ER-positive invasive breast cancer, breast cancer mortality, all-cause mortality, other cancers, cardiovascular (CV) or thromboembolic events, and fractures.
A total of 3,864 postmenopausal women at increased risk of developing breast cancer were recruited into a double-blind trial of anastrozole 1 mg/day (n=1,920) versus matching placebo (n=1,944) for 5 years. After a median follow-up of 10.9 years during which clinic visits took place, questionnaires were filled in by patients, and registry data were collected, the researchers found that women assigned to anastrozole were 50% less likely to have developed breast cancer compared with women assigned to placebo (HR 0.50; 95% CI 0.38-0.65; P<0.0001). Although the reduction was larger in the first 5 years (HR 0.39; 95% CI 0.27-0.58; P<0.0001), it was still significant after 5 years. The effects in the 2 time periods were not significantly different (P=0.11). Invasive ER-positive breast cancer was reduced by 54% with anastrozole (HR 0.46; 95% CI 0.33-0.65; P<0.0001), and a continued significant effect was seen in the post-treatment follow-up period. A non-significant effect was observed in invasive ER-negative breast cancer (HR 0.76; 95% CI 0.39-1.45; P=0.4). A reduction in DCIS overall was observed with a large reduction in ER-positive women (HR 0.23; 95% CI 0.08-0.69; P<0.0001). A total of 129 deaths were reported without significant difference in all-cause mortality between the 2 treatment arms (63 vs 66; HR 0.93; 95% CI 0.66-1.32; P=0.7). In total, 321 cancers other than breast cancer were reported, with a significant decrease observed with anastrozole (129 vs 192; OR 0.66; 95% CI 0.52-0.83; P=0.0004).
With regard to major adverse events (AEs), the results showed no increase in fractures (assessed by baseline dual energy X-ray absorptiometry [DEXA]) with anastrozole and no differences in (other) major AEs (see Table). The total number of deaths was 3.6% (n=69) with anastrozole and 3.6% (n=70) with placebo (HR 0.96; 95% CI 0.69-1.34); of these, 0.1% (n=2) and 0.2% (n=3) were due to breast cancer, respectively. Other causes of death were other cancers (1.4% [n=27] vs 1.8% [n=34]), CV causes (0.7% [n=13] vs 0.5% [n=9]), and other or unknown (1.4% [n=27] vs 1.2% [n=24]). According to the researchers, these new data show that anastrozole has a continued impact on breast cancer incidence even after stopping treatment, which strengthens the case for its use as a breast cancer prevention therapy. An estimated 29 women need to be treated with anastrozole for 5 years to prevent 1 case of breast cancer during treatment and in the following 5 years, versus the estimated 49 women to be treated with tamoxifen.
Table. Major adverse events 
1. Cuzick J, et al. GS4-04. SABCS 2019.
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Table of Contents: SABCS 2019
Screening, Detection, and Diagnosis
Phase 2 Trial Update
Phase 3 Trial Update
Long-Term Study Results
Triple-Negative Breast Cancer
HER2-Positive Breast Cancer
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