As reported by Jack Cuzick, PhD, and colleagues in The Lancet, blinded follow-up of the IBIS-II trial has shown the continued benefit of anastrozole vs placebo in preventing breast cancer in high-risk postmenopausal women during the 5-year posttreatment period.
For the international double-blind trial, 3,864 women were recruited between February 2003 and January 2012. They were randomly assigned to receive 1 mg/day of anastrozole for 5 years (n =1,920) or placebo (n = 1,944). After treatment completion, women were followed on a yearly basis. The primary outcome measure was development of histologically confirmed breast cancer, both invasive and noninvasive.
“This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the posttreatment follow-up period, with no evidence of new late side effects. Further follow-up is needed to assess the effect on breast cancer mortality.”— Jack Cuzick, PhD
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Key Findings
After a median follow-up of 131 months, breast cancer had occurred in 85 women in the anastrozole group vs 165 in the placebo group (hazard ratio [HR] = 0.51, P < .0001).
The reduction in risk with anastrozole was greater during the 5-year treatment period (35 cases vs 89 cases, HR = 0.39, P < .0001), but the reduction during the 5-year posttreatment period was still significant (50 vs 76 new cases, HR = 0.64, P = .014). The magnitudes of reduction in the two periods were not significantly different (P = .087).
Anastrozole was associated with a 54% reduction in risk of invasive estrogen receptor–positive breast cancer (HR = 0.46, P < .0001), with a 61% reduction in the first 5 years (HR = 0.39, P < .0001) followed by a 48% reduction (HR = 0.52, P = .0062) during the 5 years after treatment. Overall, anastrozole was associated with a nonsignificant reduction in risk for invasive estrogen receptor–negative breast cancer (HR = 0.77, P = .41).
Overall, anastrozole was associated with a 59% reduction in risk for ductal carcinoma in situ (HR = 0.41, P = .0081), with the reduction being particularly marked for cases known to be estrogen receptor–positive (HR = 0.22, P < .0001).
No significant differences in overall mortality (69 vs 70 deaths, HR = 0.96, P = .82) or mortality due to breast cancer (two vs three deaths) were observed.
Overall, anastrozole was associated with a significantly reduced risk of cancers other than breast cancer (147 vs 200 cases, odds ratio = 0.72, P = .0042), primarily reflecting reduced risk of nonmelanoma skin cancers.
No excess risk of fractures or cardiovascular disease was observed in the anastrozole group.
The investigators concluded, “This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the posttreatment follow-up period, with no evidence of new late side effects. Further follow-up is needed to assess the effect on breast cancer mortality.”
Dr. Cuzick, of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
