Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Jack Cuzick; Ivana Sestak; John F. Forbes; Mitch Dowsett; Jill Knox; Simon Cawthorn; Christobel Saunders; Nicola Roche; Robert E. Mansel; Gunter von Minckwitz; Bernardo Bonanni; Tiina Palva; Anthony Howell; IBIS-II investigators

doi:10.1016/S0140-6736(13)62292-8

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Jack Cuzick (Corresponding Author), Ivana Sestak, John F. Forbes, Mitch Dowsett, Jill Knox, Simon Cawthorn, Christobel Saunders, Nicola Roche, Robert E. Mansel, Gunter von Minckwitz, Bernardo Bonanni, Tiina Palva, Anthony Howell, IBIS-II investigators

School of Medicine, Medical Sciences & Nutrition

Research output: Contribution to journal › Article › peer-review

443 Citations (Scopus)

7 Downloads (Pure)

Abstract

BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.

FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 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. 18 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).

INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.

FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

Original language	English
Pages (from-to)	1041-1048
Number of pages	8
Journal	The Lancet
Volume	383
Issue number	9922
Early online date	12 Dec 2013
DOIs	https://doi.org/10.1016/S0140-6736(13)62292-8
Publication status	Published - 22 Mar 2014

Bibliographical note

This study was funded by Cancer Research UK (C569/A5032), the National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca. Sanofi-Aventis and AstraZeneca provided anastrozole and matching placebo. The study sponsor was Queen Mary University of London.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/S0140-6736(13)62292-8Licence: CC BY

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial
© Cuzick et al. Open Access article distributed under the terms of CC BY https://creativecommons.org/licenses/by/3.0/
Final published version, 452 KBLicence: CC BY

Cite this

Cuzick, J., Sestak, I., Forbes, J. F., Dowsett, M., Knox, J., Cawthorn, S., Saunders, C., Roche, N., Mansel, R. E., von Minckwitz, G., Bonanni, B., Palva, T., Howell, A., & IBIS-II investigators (2014). Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. The Lancet, 383(9922), 1041-1048. https://doi.org/10.1016/S0140-6736(13)62292-8

Cuzick, J, Sestak, I, Forbes, JF, Dowsett, M, Knox, J, Cawthorn, S, Saunders, C, Roche, N, Mansel, RE, von Minckwitz, G, Bonanni, B, Palva, T, Howell, A & IBIS-II investigators 2014, 'Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial', The Lancet, vol. 383, no. 9922, pp. 1041-1048. https://doi.org/10.1016/S0140-6736(13)62292-8

@article{a9a8da326b944a389a782d0e94c0cd48,

title = "Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial",

abstract = "BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 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. 18 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).INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.",

author = "Jack Cuzick and Ivana Sestak and Forbes, {John F.} and Mitch Dowsett and Jill Knox and Simon Cawthorn and Christobel Saunders and Nicola Roche and Mansel, {Robert E.} and {von Minckwitz}, Gunter and Bernardo Bonanni and Tiina Palva and Anthony Howell and {IBIS-II investigators}",

note = "This study was funded by Cancer Research UK (C569/A5032), the National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca. Sanofi-Aventis and AstraZeneca provided anastrozole and matching placebo. The study sponsor was Queen Mary University of London.",

year = "2014",

month = mar,

day = "22",

doi = "10.1016/S0140-6736(13)62292-8",

language = "English",

volume = "383",

pages = "1041--1048",

journal = "The Lancet",

issn = "0140-6736",

publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",

number = "9922",

}

TY - JOUR

T1 - Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II)

T2 - an international, double-blind, randomised placebo-controlled trial

AU - Cuzick, Jack

AU - Sestak, Ivana

AU - Forbes, John F.

AU - Dowsett, Mitch

AU - Knox, Jill

AU - Cawthorn, Simon

AU - Saunders, Christobel

AU - Roche, Nicola

AU - Mansel, Robert E.

AU - von Minckwitz, Gunter

AU - Bonanni, Bernardo

AU - Palva, Tiina

AU - Howell, Anthony

AU - IBIS-II investigators

N1 - This study was funded by Cancer Research UK (C569/A5032), the National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca. Sanofi-Aventis and AstraZeneca provided anastrozole and matching placebo. The study sponsor was Queen Mary University of London.

PY - 2014/3/22

Y1 - 2014/3/22

N2 - BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 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. 18 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).INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

AB - BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 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. 18 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).INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

U2 - 10.1016/S0140-6736(13)62292-8

DO - 10.1016/S0140-6736(13)62292-8

M3 - Article

C2 - 24333009

SN - 0140-6736

VL - 383

SP - 1041

EP - 1048

JO - The Lancet

JF - The Lancet

IS - 9922

ER -

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Abstract

Bibliographical note

UN SDGs

Access to Document

Fingerprint

Cite this