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

NCT00078832 | Completed Phase 3 DMC

• 3 other identifiers: ISRCTN31488319EU-20227EUDRACT-2004-003991-12
• Study Type: interventional
• Target: 3,864
• Locations: 14 countries
• Sites: 74

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.

Conditions

Breast Cancer

Keywords

breast cancer, chemoprevention

Outcome Measures

Primary Outcomes (1)

• Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years

  Dec 2013

Secondary Outcomes (1)

• Breast cancer mortality with median follow-up at 10 years

  Dec 2018

Study Arms (2)

anastrozole

EXPERIMENTAL

anastrozole 1mg

Drug: anastrozole

placebo

PLACEBO COMPARATOR

anastrozole 1mg PLACEBO

Drug: placebo

Interventions

anastrozole DRUG

aromatase inhibitor

Also known as: Arimidex

anastrozole

placebo DRUG

Arimidex placebo

placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (74)

Newcastle Mater Hospital

Newcastle, New South Wales, 2310, Australia

Location

University Hospitals

Leuven, B-3000, Belgium

Location

Corporacion Nacional del Cancer

Santiago, Chile

Location

Herlev University Hospital

Hørsholm, Dk- 2730 Herlev, Denmark

Location

Pirkanmaa Cancer Society

Tampere, 33100, Finland

Location

GBG Forschungs GMBH

Frankfurt, 63263, Germany

Location

Department of Oncotherapy, University of Szeged

Szeged, 6720, Hungary

Location

Beaumont Hospital

Dublin, Beaumont, 9, Ireland

Location

Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital

Dublin, Tallaght, 24, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

South Infirmary Victoria Hospital

Cork, Ireland

Location

St. Vincent's University Hospital

Dublin, 4, Ireland

Location

St. James's Hospital

Dublin, 8, Ireland

Location

University College Hospital

Galway, Ireland

Location

Mid-Western Cancer Centre at Mid-Western Regional Hospital

Limerick, 0009, Ireland

Location

Sligo General Hospital

Sligo, Ireland

Location

Division of Chemoprevention

Milan, 20141, Italy

Location

Sir Paul Boffa Hospital, Harper Lane

Floriana, VLT 14, Malta

Location

Instituto Portugues De Oncologia, Gabinete De Estudos Clinicos

Lisbon, 1099-023, Portugal

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Oncocare Sonnenhof-Klinik Engeriedspital

Bern, CH-3012, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Tumor Zentrum ZeTup St. Gallen und Chur

Sankt Gallen, CH-9006, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Ortaklar cad Pehlivan sok, Basak koviah ap.

Istanbul, Turkey (Türkiye)

Location

Tameside General Hospital

Ashton-under-Lyne, England, OL6 9RW, United Kingdom

Location

Royal Bolton Hospital

Bolton, England, BL4 0JR, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

Location

St. Luke's Hospital

Bradford, England, BD5 0NA, United Kingdom

Location

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, BN2 5BE, United Kingdom

Location

Frenchay Hospital

Bristol, England, BS16 1LE, United Kingdom

Location

Bristol Royal Infirmary

Bristol, England, BS2 8HW, United Kingdom

Location

Queen's Hospital

Burton-on-Trent, England, DE13 0RB, United Kingdom

Location

Broomfield Hospital

Chelmsford, England, CM1 7ET, United Kingdom

Location

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, GL53 7AN, United Kingdom

Location

Countess of Chester Hospital

Chester, England, CH2 1UL, United Kingdom

Location

Essex County Hospital

Colchester, England, C03 3NB, United Kingdom

Location

Royal Derby Hospital

Derby, England, DE1 2QY, United Kingdom

Location

Saint Margaret's Hospital,

Epping, England, CM16 6TN, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, England, EX2 5DW, United Kingdom

Location

Frimley Park Hospital

Frimley, England, GU16 7UJ, United Kingdom

Location

Conquest Hospital

Hastings, England, TN37 7RD, United Kingdom

Location

Castle Hill Hospital

Hull, England, HU16 5JQ, United Kingdom

Location

Airedale General Hospital

Keighley, England, BD20 6TD, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Lincoln County Hospital

Lincoln, England, LN2 5QY, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

Guy's Hospital

London, England, SE1 9RT, United Kingdom

Location

Royal Marsden - London

London, England, SW3 6JJ, United Kingdom

Location

Macclesfield District General Hospital

Macclesfield, England, SK10 3BL, United Kingdom

Location

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Singleton Hospital

Swansea, Wales, SA2 8QA, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZA, United Kingdom

Location

Lincoln County Hospital

Grantham, LN2 5QY, United Kingdom

Location

Calderdale Royal Hospital

Huddersfield, HX3 0PW, United Kingdom

Location

Royal Free and UCL Medical School

London, N19 5LW, United Kingdom

Location

Paterson Institute for Cancer Research

Manchester, M20 4BX, United Kingdom

Location

Northwick Park Hospital

Middlesex, HA1 3UJ, United Kingdom

Location

School of Surgical & Reproductive Sciences

Newcastle, NE2 4HH, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Department of General Surgery Pennine Acute Hospitals NHS Trust

Oldham, OL1 2JH, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Cancer Clinical Trials Centre

Sheffield, S10 2SJ, United Kingdom

Location

Weston Park Hospital, Cancer Clinical Trials Centre, Department of Clinical Oncology

Sheffield, S10 2SJ, United Kingdom

Location

Princess Anne Hospital

Southampton, SO16 5YA, United Kingdom

Location

Mid Staffordshire NHS Foundation Trust

Stafford, ST16 3SA, United Kingdom

Location

Treliske Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

Wishaw General Hospital

Wishaw, ML2 0DP, United Kingdom

Location

Yeovil District Hospital

Yeovil, BA21 4AT, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 25456365 BACKGROUND

• 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.

  PMID: 18768369 BACKGROUND

• 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.

  PMID: 29126161 BACKGROUND

• 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.

  PMID: 24333009 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jack Cuzick, PhD

  Queen Mary University of London

  STUDY CHAIR

• Anthony Howell

  University of Manchester

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 9, 2004
• Study Start: September 1, 2003
• Primary Completion: December 1, 2013
• Study Completion: May 31, 2021
• Last Updated: October 6, 2021

Record last verified: 2018-04

Locations

BE (1); IT (1); TU (1); GB (48); HU (1); DK (1); CL (1); MA (1); PT (1); FI (1); CH (6); AU (1); DE (1); IE (9)