IBIS II: Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer

• Sponsor: Queen Mary University of London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00078832
• Collaborator: (none)
• Enrollment: 3,864
• Locations: 74
• Arms: 2
• Duration (Months): 213
• Patients Per Site: 52.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: anastrozole; Drug: placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3864 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: International Breast Cancer Intervention Study
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: anastrozole anastrozole 1mg	Drug: anastrozole; aromatase inhibitor; Other Names: Arimidex
Placebo Comparator: placebo anastrozole 1mg PLACEBO	Drug: placebo; Arimidex placebo

Outcome Measures

Primary Outcome Measures

1. Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years [Dec 2013]

Secondary Outcome Measures

1. Breast cancer mortality with median follow-up at 10 years [Dec 2018]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Newcastle Mater Hospital	Newcastle	New South Wales	Australia	2310
2	University Hospitals	Leuven		Belgium	B-3000
3	Corporacion Nacional del Cancer	Santiago		Chile
4	Herlev University Hospital	Horsholm		Denmark	Dk- 2730 Herlev
5	Pirkanmaa Cancer Society	Tampere		Finland	33100
6	GBG Forschungs GMBH	Frankfurt		Germany	63263
7	Department of Oncotherapy, University of Szeged	Szeged		Hungary	6720
8	Beaumont Hospital	Dublin	Beaumont	Ireland	9
9	Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital	Dublin	Tallaght	Ireland	24
10	Cork University Hospital	Cork		Ireland
11	South Infirmary Victoria Hospital	Cork		Ireland
12	St. Vincent's University Hospital	Dublin		Ireland	4
13	St. James's Hospital	Dublin		Ireland	8
14	University College Hospital	Galway		Ireland
15	Mid-Western Cancer Centre at Mid-Western Regional Hospital	Limerick		Ireland	0009
16	Sligo General Hospital	Sligo		Ireland
17	Division of Chemoprevention	Milan		Italy	20141
18	Sir Paul Boffa Hospital, Harper Lane	Floriana		Malta	VLT 14
19	Instituto Portugues De Oncologia, Gabinete De Estudos Clinicos	Lisbon		Portugal	1099-023
20	Inselspital Bern	Bern		Switzerland	CH-3010
21	Oncocare Sonnenhof-Klinik Engeriedspital	Bern		Switzerland	CH-3012
22	Hopital Cantonal Universitaire de Geneve	Geneva		Switzerland	CH-1211
23	Ospedale Beata Vergine	Mendrisio		Switzerland	CH-6850
24	Tumor Zentrum ZeTup St. Gallen und Chur	St. Gallen		Switzerland	CH-9006
25	Regionalspital	Thun		Switzerland	3600
26	Ortaklar cad Pehlivan sok, Basak koviah ap.	Istanbul		Turkey
27	Tameside General Hospital	Ashton-Under-Lyne	England	United Kingdom	OL6 9RW
28	Royal Bolton Hospital	Bolton	England	United Kingdom	BL4 0JR
29	Royal Bournemouth Hospital	Bournemouth	England	United Kingdom	BH7 7DW
30	St. Luke's Hospital	Bradford	England	United Kingdom	BD5 0NA
31	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England	United Kingdom	BN2 5BE
32	Frenchay Hospital	Bristol	England	United Kingdom	BS16 1LE
33	Bristol Royal Infirmary	Bristol	England	United Kingdom	BS2 8HW
34	Queen's Hospital	Burton-upon-Trent	England	United Kingdom	DE13 0RB
35	Broomfield Hospital	Chelmsford	England	United Kingdom	CM1 7ET
36	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England	United Kingdom	GL53 7AN
37	Countess of Chester Hospital	Chester	England	United Kingdom	CH2 1UL
38	Essex County Hospital	Colchester	England	United Kingdom	C03 3NB
39	Royal Derby Hospital	Derby	England	United Kingdom	DE1 2QY
40	Saint Margaret's Hospital,	Epping	England	United Kingdom	CM16 6TN
41	Royal Devon and Exeter Hospital	Exeter	England	United Kingdom	EX2 5DW
42	Frimley Park Hospital	Frimley	England	United Kingdom	GU16 7UJ
43	Conquest Hospital	Hastings	England	United Kingdom	TN37 7RD
44	Castle Hill Hospital	Hull	England	United Kingdom	HU16 5JQ
45	Airedale General Hospital	Keighley	England	United Kingdom	BD20 6TD
46	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
47	Lincoln County Hospital	Lincoln	England	United Kingdom	LN2 5QY
48	Royal Liverpool University Hospital	Liverpool	England	United Kingdom	L7 8XP
49	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
50	Guy's Hospital	London	England	United Kingdom	SE1 9RT
51	Royal Marsden - London	London	England	United Kingdom	SW3 6JJ
52	Macclesfield District General Hospital	Macclesfield	England	United Kingdom	SK10 3BL
53	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland	United Kingdom	BT9 7AB
54	Ninewells Hospital	Dundee	Scotland	United Kingdom	DD1 9SY
55	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
56	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XW
57	Singleton Hospital	Swansea	Wales	United Kingdom	SA2 8QA
58	Aberdeen Royal Infirmary	Aberdeen		United Kingdom	AB25 2ZA
59	Lincoln County Hospital	Grantham		United Kingdom	LN2 5QY
60	Calderdale Royal Hospital	Huddersfield		United Kingdom	HX3 0PW
61	Royal Free and UCL Medical School	London		United Kingdom	N19 5LW
62	Paterson Institute for Cancer Research	Manchester		United Kingdom	M20 4BX
63	Northwick Park Hospital	Middlesex		United Kingdom	HA1 3UJ
64	School of Surgical & Reproductive Sciences	Newcastle		United Kingdom	NE2 4HH
65	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom	NG5 1PB
66	Department of General Surgery Pennine Acute Hospitals NHS Trust	Oldham		United Kingdom	OL1 2JH
67	Derriford Hospital	Plymouth		United Kingdom	PL6 8DH
68	Cancer Clinical Trials Centre	Sheffield		United Kingdom	S10 2SJ
69	Weston Park Hospital, Cancer Clinical Trials Centre, Department of Clinical Oncology	Sheffield		United Kingdom	S10 2SJ
70	Princess Anne Hospital	Southampton		United Kingdom	SO16 5YA
71	Mid Staffordshire NHS Foundation Trust	Stafford		United Kingdom	ST16 3SA
72	Treliske Royal Cornwall Hospital	Truro		United Kingdom	TR1 3LJ
73	Wishaw General Hospital	Wishaw		United Kingdom	ML2 0DP
74	Yeovil District Hospital	Yeovil		United Kingdom	BA21 4AT

Sponsors and Collaborators

• Queen Mary University of London

Investigators

• Study Chair: Jack Cuzick, PhD, Queen Mary University of London
• Study Chair: Anthony Howell, University of Manchester

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• 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.
• 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.
• 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.
• 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.

• Responsible Party: Queen Mary University of London
• ClinicalTrials.gov Identifier: NCT00078832
• Other Study ID Numbers: ISRCTN31488319; EU-20227; EUDRACT-2004-003991-12
• First Posted: Mar 9, 2004
• Last Update Posted: Oct 6, 2021
• Last Verified: Apr 1, 2018

• Keywords provided by Queen Mary University of London: breast cancer, chemoprevention
• Additional relevant MeSH terms: Breast Neoplasms; Anastrozole

Study Results

No Results Posted as of Oct 6, 2021