TY  - JOUR
A1  - Cuzick, Jack
A1  - Sestak, Ivana
A1  - Forbes, John Frederick
A1  - Dowsett, Mitch
A1  - Cawthorn, Simon
A1  - Mansel, Robert E.
A1  - Loibl, Sibylle
A1  - Bonanni, Bernardo
A1  - Evans, D. Gareth
A1  - Howell, Anthony
T1  - Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial
T2  - The lancet
N2  - Background: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period.
Methods: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer.
Findings: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105–156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39–0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27–0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45–0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33–0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22–0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78–0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69–1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57–0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed.
Interpretation: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.
Funding: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53139
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-531392
SN  - 1474-547X
SN  - 0140-6736
N1  - Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
N1  - Erratum erschienen in: The lancet, 395.2020, Nr. 10233, S. 496, doi:10.1016/S0140-6736(20)30323-8
VL  - 395
IS  - 10218
SP  - 117
EP  - 122
PB  - Elsevier
CY  - London [u. a.]
ER  -