Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer

Breast Cancer Clinical Trial

— IBIS II  

Official title:

International Breast Cancer Intervention Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00078832
• Other study ID #: ISRCTN31488319
• Secondary ID: EU-20227EUDRACT-
• Status: Completed
• Phase: Phase 3
• Start date: September 2003
• Est. completion date: May 31, 2021

Study information

• Verified date: April 2018
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Anastrozole may be effective in preventing breast cancer.

PURPOSE: This randomized clinical trial is studying how well anastrozole works in preventing breast cancer in postmenopausal women who are at increased risk for the disease.

Description:

OBJECTIVES:

Primary

• Determine the effectiveness of anastrozole in preventing breast cancer in postmenopausal women at increased risk for the disease.

Secondary

• Determine the role of this drug in preventing estrogen receptor-positive breast cancer in these participants.

• Determine the effect of this drug on breast cancer mortality in these participants.

• Determine the effect of this drug on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these participants.

• Determine the tolerability and acceptability of side effects of this drug in these participants.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to participating center. Participants are randomized to 1 of 2 treatment arms.

• Arm I: Participants receive oral anastrozole daily for 5 years.

• Arm II: Participants receive an oral placebo daily for 5 years. In both arms, treatment continues in the absence of the development of breast cancer (including ductal carcinoma in situ), a drop in the T-score below minus 4, or the occurrence of a new fragility fracture.

Participants are followed for at least a further 5 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

ACCRUAL: A total of 3,864 participants were recruited for this study over 10 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3864
• Est. completion date: May 31, 2021
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 70 Years

Eligibility

DISEASE CHARACTERISTICS:

• Meets at least 1 of the relative risk factors based on age as follows:

• 45 to 70 years of age:

• First-degree relative who developed breast cancer at = 50 years of age

• First-degree relative who developed bilateral breast cancer

• Two or more first- or second-degree relatives who developed breast cancer or ovarian cancer

• Participants having both relatives who are second degree and on the opposite sides of the family must have at least one that was diagnosed at = 50 years of age

• Nulliparous (or first birth at = 30 years of age) and a first-degree relative who developed breast cancer

• Benign biopsy with proliferative disease and a first-degree relative who developed breast cancer

• Mammographic opacity covering at least 50% of the breast in the absence of hormone replacement therapy within the past 3 months

• 60 to 70 years of age:

• First-degree relative with breast cancer at any age

• Age at menopause = 55 years

• Nulliparous or age at first birth = 30 years

• 40 to 44 years of age:

• Two or more first- or second-degree relatives who developed breast cancer or ovarian cancer at = 50 years of age

• First-degree relative with bilateral breast cancer who developed the first breast cancer at = 50 years of age

• Nulliparous (or first birth at = 30 years of age) and a first-degree relative who developed breast cancer at = 40 years of age

• Benign biopsy with proliferative disease and a first-degree relative who developed breast cancer at = 40 years of age

• All age groups (40 to 70 ears of age) with a 10-year risk > 5% who do not fit into the above categories are allowed

• Clearly apparent family history AND/OR other risk factors indicating appropriate increased risk of breast cancer for age

• The following prior breast conditions are allowed (for all age groups):

• Lobular carcinoma in situ

• Atypical ductal or lobular hyperplasia in a benign lesion

• Ductal carcinoma in-situ (DCIS), diagnosed within the past 6 months, and treated by mastectomy

• No evidence of breast cancer on mammogram within the past year

• Hormone receptor status:

• For patients with prior DCIS, estrogen- or progesterone-receptor status must have been positive

• Must have had greater than or equal to 5% positive cells

PATIENT CHARACTERISTICS:

Age

• 40 to 70

Sex

• Female

Menopausal status

• Postmenopausal, defined as at least 1 of the following:

• Over 60 years of age

• Bilateral oophorectomy

• = 60 years of age with a uterus and amenorrhea for at least 12 months

• = 60 years of age without a uterus and with follicle-stimulating hormone levels > 30 IU/L

Performance status

• Not specified

Life expectancy

• At least 10 years

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Psychologically and physically suitable to receive 5 years of anti-estrogen therapy

• No cancer within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix

• No evidence of osteoporosis or fragility fractures within the spine

• Participants with a T-score > minus 4 and no more than 2 fragility fractures are allowed

• No concurrent severe disease that would place the participant at unusual risk or confound the results of the study

• No other medical condition that would preclude the ability to receive the study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No prior tamoxifen, raloxifene, or other selective estrogen receptor modulator (SERM) use for more than 6 months in duration unless an IBIS-I participant (must have been off trial therapy for at least 5 years.

• No concurrent tamoxifen, raloxifene, or other SERM

• No concurrent estrogen-based hormone replacement therapy

• No concurrent systemic estrogen replacement therapy, including vaginal estrogen preparations

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

• No prior prophylactic mastectomy

• No concurrent prophylactic mastectomy

Other

• More than 6 months since prior investigational drugs

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• anastrozole
aromatase inhibitor
• placebo
Arimidex placebo

Locations

Country	Name	City	State
Australia	Newcastle Mater Hospital	Newcastle	New South Wales
Belgium	University Hospitals	Leuven
Chile	Corporacion Nacional del Cancer	Santiago
Denmark	Herlev University Hospital	Horsholm
Finland	Pirkanmaa Cancer Society	Tampere
Germany	GBG Forschungs GMBH	Frankfurt
Hungary	Department of Oncotherapy, University of Szeged	Szeged
Ireland	Cork University Hospital	Cork
Ireland	South Infirmary Victoria Hospital	Cork
Ireland	Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital	Dublin	Tallaght
Ireland	Beaumont Hospital	Dublin	Beaumont
Ireland	St. James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	University College Hospital	Galway
Ireland	Mid-Western Cancer Centre at Mid-Western Regional Hospital	Limerick
Ireland	Sligo General Hospital	Sligo
Italy	Division of Chemoprevention	Milan
Malta	Sir Paul Boffa Hospital, Harper Lane	Floriana
Portugal	Instituto Portugues De Oncologia, Gabinete De Estudos Clinicos	Lisbon
Switzerland	Inselspital Bern	Bern
Switzerland	Oncocare Sonnenhof-Klinik Engeriedspital	Bern
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Tumor Zentrum ZeTup St. Gallen und Chur	St. Gallen
Switzerland	Regionalspital	Thun
Turkey	Ortaklar cad Pehlivan sok, Basak koviah ap.	Istanbul
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Tameside General Hospital	Ashton-Under-Lyne	England
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Royal Bolton Hospital	Bolton	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	St. Luke's Hospital	Bradford	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Royal Infirmary	Bristol	England
United Kingdom	Frenchay Hospital	Bristol	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Broomfield Hospital	Chelmsford	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Countess of Chester Hospital	Chester	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Royal Derby Hospital	Derby	England
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Saint Margaret's Hospital,	Epping	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Frimley Park Hospital	Frimley	England
United Kingdom	Lincoln County Hospital	Grantham
United Kingdom	Conquest Hospital	Hastings	England
United Kingdom	Calderdale Royal Hospital	Huddersfield
United Kingdom	Castle Hill Hospital	Hull	England
United Kingdom	Airedale General Hospital	Keighley	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Lincoln County Hospital	Lincoln	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Royal Free and UCL Medical School	London
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Macclesfield District General Hospital	Macclesfield	England
United Kingdom	Paterson Institute for Cancer Research	Manchester
United Kingdom	Northwick Park Hospital	Middlesex
United Kingdom	School of Surgical & Reproductive Sciences	Newcastle
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Department of General Surgery Pennine Acute Hospitals NHS Trust	Oldham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Cancer Clinical Trials Centre	Sheffield
United Kingdom	Weston Park Hospital, Cancer Clinical Trials Centre, Department of Clinical Oncology	Sheffield
United Kingdom	Princess Anne Hospital	Southampton
United Kingdom	Mid Staffordshire NHS Foundation Trust	Stafford
United Kingdom	Singleton Hospital	Swansea	Wales
United Kingdom	Treliske Royal Cornwall Hospital	Truro
United Kingdom	Wishaw General Hospital	Wishaw
United Kingdom	Yeovil District Hospital	Yeovil

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

Countries where clinical trial is conducted

Australia,  Belgium,  Chile,  Denmark,  Finland,  Germany,  Hungary,  Ireland,  Italy,  Malta,  Portugal,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (4)

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. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014 Mar 22;383(9922):1041-8. doi: 10.1016/S0140-6736(13)62292-8. Epub 2013 Dec 12. Erratum in: Lancet. 2014 Mar 22;383(9922):1040. Erratum in: Lancet. 2017 Mar 11;389(10073):1010. — View Citation

Jenkins VA, Ambroisine LM, Atkins L, Cuzick J, Howell A, Fallowfield LJ. Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet Oncol. 2008 Oct;9(10):953-61. doi: 10.1016/S1470-2045(08)70207-9. Epub 2008 Sep 1. — View Citation

Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F, Coleman R, Dowsett M, Forbes JF, Howell A, Eastell R. Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2014 Dec;15(13):1460-1468. doi: 10.1016/S1470-2045(14)71035-6. Epub 2014 Nov 11. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. — View Citation

Sestak I, Smith SG, Howell A, Forbes JF, Cuzick J. Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II. Ann Oncol. 2018 Feb 1;29(2):504-509. doi: 10.1093/annonc/mdx713. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years		Dec 2013
Secondary	Breast cancer mortality with median follow-up at 10 years		Dec 2018

External Links

•   Clinical trial summary from Cancer Research UK Website
•   IBIS-II website