Clinical trial NCT00078832: Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer
Official title: International Breast Cancer Intervention Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast cancer, chemoprevention
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2004-03-09
Enrollment: 3864
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
timeFrame: Dec 2013
Secondary outcomes:
measure: Breast cancer mortality with median follow-up at 10 years
timeFrame: Dec 2018
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: Newcastle Mater Hospital
state: New South Wales
city: Leuven
country: Belgium
facility: University Hospitals
city: Santiago
country: Chile
facility: Corporacion Nacional del Cancer
city: Horsholm
country: Denmark
facility: Herlev University Hospital
city: Tampere
country: Finland
facility: Pirkanmaa Cancer Society
city: Frankfurt
country: Germany
facility: GBG Forschungs GMBH
city: Szeged
country: Hungary
facility: Department of Oncotherapy, University of Szeged
city: Dublin
country: Ireland
facility: Beaumont Hospital
state: Beaumont
city: Dublin
country: Ireland
facility: Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
state: Tallaght
city: Cork
country: Ireland
facility: Cork University Hospital
city: Cork
country: Ireland
facility: South Infirmary Victoria Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Galway
country: Ireland
facility: University College Hospital
city: Limerick
country: Ireland
facility: Mid-Western Cancer Centre at Mid-Western Regional Hospital
city: Sligo
country: Ireland
facility: Sligo General Hospital
city: Milan
country: Italy
facility: Division of Chemoprevention
city: Floriana
country: Malta
facility: Sir Paul Boffa Hospital, Harper Lane
city: Lisbon
country: Portugal
facility: Instituto Portugues De Oncologia, Gabinete De Estudos Clinicos
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Bern
country: Switzerland
facility: Oncocare Sonnenhof-Klinik Engeriedspital
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Mendrisio
country: Switzerland
facility: Ospedale Beata Vergine
city: St. Gallen
country: Switzerland
facility: Tumor Zentrum ZeTup St. Gallen und Chur
city: Thun
country: Switzerland
facility: Regionalspital
city: Istanbul
country: Turkey
facility: Ortaklar cad Pehlivan sok, Basak koviah ap.
city: Ashton-Under-Lyne
country: United Kingdom
facility: Tameside General Hospital
state: England
city: Bolton
country: United Kingdom
facility: Royal Bolton Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bradford
country: United Kingdom
facility: St. Luke's Hospital
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Frenchay Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
state: England
city: Epping
country: United Kingdom
facility: Saint Margaret's Hospital,
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital
state: England
city: Hastings
country: United Kingdom
facility: Conquest Hospital
state: England
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Keighley
country: United Kingdom
facility: Airedale General Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
state: England
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Queen's University Belfast
state: Northern Ireland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Grantham
country: United Kingdom
facility: Lincoln County Hospital
city: Huddersfield
country: United Kingdom
facility: Calderdale Royal Hospital
city: London
country: United Kingdom
facility: Royal Free and UCL Medical School
city: Manchester
country: United Kingdom
facility: Paterson Institute for Cancer Research
city: Middlesex
country: United Kingdom
facility: Northwick Park Hospital
city: Newcastle
country: United Kingdom
facility: School of Surgical & Reproductive Sciences
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oldham
country: United Kingdom
facility: Department of General Surgery Pennine Acute Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Cancer Clinical Trials Centre
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital, Cancer Clinical Trials Centre, Department of Clinical Oncology
city: Southampton
country: United Kingdom
facility: Princess Anne Hospital
city: Stafford
country: United Kingdom
facility: Mid Staffordshire NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Treliske Royal Cornwall Hospital
city: Wishaw
country: United Kingdom
facility: Wishaw General Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
Study officials:
affiliation: Queen Mary University of London
name: Jack Cuzick, PhD
role: STUDY_CHAIR
affiliation: University of Manchester
name: Anthony Howell
role: STUDY_CHAIR
References:
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.
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.
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.
citation: 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.