In The Lancet, researchers report the first results from IBIS-II (International Breast cancer Intervention Study II) in which 3864 postmenopausal women at high risk of breast cancer were randomised to receive preventative treatment with anastrozole 1mg (n=1920) or placebo (n=1944) every day for 5 years. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ).
At 5 years, 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0.47, 95% CI, 0.32—0.68, p<0.0001). The predicted cumulative incidence of all breast cancers after 7 years was 5.6% in the placebo group and 2.8% in the anastrozole group. Eighteen deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0.836).
Many adverse events were reported. Total number of fractures did not differ significantly by group. Musculoskeletal adverse events were reported in significantly more women in the anastrozole group than in the placebo group (p=0.0001). Carpal tunnel syndrome and joint stiffness were both significantly more common in the anastrozole group than in the placebo group. Vasomotor symptoms were common in both groups, but significantly more frequent with anastrozole than placebo (p<0.0001). Significantly more women taking anastrozole than those taking placebo reported dry eyes. Hypertension wassignificantly increased with anastrozole.
Full adherence for 5 years was 70% overall and only slightly lower in the anastrozole group than in the placebo group.
The researchers note that the median follow-up in their study of 5 years is longer than for previous trials but further follow-up is needed to fully assess the value of anastrozole in the prevention setting, though a commentary notes that without protocol-defined procedures after 5 years, complete data capture might be a challenge.
The American Society of Clinical Oncology task force has recommended that exemestane be considered for prevention in addition to tamoxifen and raloxifene, whilst NICE has recommended that tamoxifen and raloxifene be offered to women at high risk of breast cancer. The researchers conclude that their findings strongly support the use of anastrozole for preventive treatment of high-risk post menopausal women.
An accompanying commentary points out that as the strongest protective effect was recorded in hormone-sensitive and screen-detected breast cancers, the overall breast cancer mortality gain with prevention therapy could be small; and no such gain has been reported in any of the pharmacoprevention trials to date. Therefore, for any woman considering 5 years anti-oestrogen therapy to reduce breast cancer risk without evidence of longer life, the perceived and actual toxicity of this intervention becomes important.