- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00002644
Tamoxifen for the Prevention of Breast Cancer in High-Risk Women (IBIS-1)
International Breast Cancer Intervention Study: A Multicentre Trial of Tamoxifen to Prevent Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Established in 1992, the IBIS-I Study investigated the efficacy of tamoxifen (a hormonal drug used to prevent breast cancer) versus a placebo drug (taken daily for five years) in terms of reduction of breast cancer incidence in pre and postmenopausal women at high risk of developing breast cancer. It was a double-blind, randomised placebo-controlled trial that recruited 7,154 women internationally (of which 4,277 were UK participants), aged 35-70 years. The primary outcome measure was the incidence of breast cancer, including ductal carcinoma in situ (cancer cells in the lining of the breast milk duct) and side effects present in the patients were also investigated.
Recruitment to the study completed in 2001 and the intervention (placebo/tamoxifen) ended in 2007. In early 2008 the Research Ethics Committee (REC) approved the conversion of IBIS-I to an epidemiological cohort study. During 2007-2016 participants were followed-up via an annual postal questionnaire.
In 2002, initial results found that tamoxifen reduced the risk of invasive breast cancer by 31%. Mortality from non-breast cancer causes was not increased by tamoxifen. However, the analysis concluded that the overall risk/benefit ratio for the use of tamoxifen in prevention remained unclear and that continued follow-up of trial participants was essential. A 2007 analysis on long-term tamoxifen prophylaxis for breast cancer confirmed the preventive effect of tamoxifen in terms of breast cancer incidence and that this was constant for the entire follow-up period. No reduction in size of benefit was observed for up to ten years following participant randomisation. Additionally, tamoxifen-related side effects such as thrombo-embolism were not increased anymore after the 5-year treatment period. These results therefore demonstrate that the benefit-to-risk ratio of tamoxifen improves with increasing duration of follow-up. Thus, how much additional benefit will be seen long-term remains an important question.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
England
-
London, England, United Kingdom, EC1M6BQ
- Queen Mary University of London
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
The entry criteria are based on a relative risk of at least two-fold for women aged 45-70 years, four-fold for women aged 40-44 years and ten-fold for women aged 35-39 years.
Age 45-70 years
- First degree relative who developed breast cancer at age 50 or less
- First degree relative who developed bilateral breast cancer
- Two or more first or second degree relatives who developed breast cancer
- Nulliparous and a first degree relative who developed breast cancer
- Benign biopsy with proliferative disease and a first degree relative who developed breast cancer
- Lobular carcinoma in situ
- Atypical ductal or lobular hyperplasia in a benign lesion
19)Women at high risk who do not fit into the above categories (risk equivalent)*
* These women must have clearly apparent family history indicating at least two fold increased risk of breast cancer.
Age 40-44 years 8) Two or more first or second degree relatives who developed breast cancer at age 50 or less 9) First degree relative with bilateral breast cancer who developed the first breast cancer at age 50 or less 10) Nulliparous and a first degree relative who developed breast cancer at age 40 or less 11) Benign biopsy with proliferative disease and a first degree relative who developed breast cancer at age 40 or less 12) Lobular carcinoma in situ 13) Atypical ductal or lobular hyperplasia in a benign lesion 14) Women at high risk who do not fit into the above categories (risk equivalent)*
* These women must have clearly apparent family history indicating at least four fold increased risk of breast cancer.
Age 35-39 years 15) Two or more first degree relatives who developed breast cancer at age 50 or less 16) First degree relative with bilateral breast cancer who developed the first breast cancer at age 40 or less 17) Lobular carcinoma in situ 18) Women at high risk who do not fit into the above categories (risk equivalent)*
Exclusion criteria:
- Pregnant, or at pregnancy risk. If necessary, pre and peri menopausal women must use non-hormonal contraception during the trial.
- Any previous cancer (except non-melanoma skin cancer or in situ cancer of the cervix).
- Life expectancy of less than 10 years or other medical condition more serious than the risk of breast cancer.
- Psychologically and physically unsuitable for five years tamoxifen/placebo therapy.
- Current treatment with anti-coagulants.
- Previous deep vein thrombosis or pulmonary embolus.
- Current tamoxifen use.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tamoxifen citrate
Tamoxifen citrate 20 mg/day for 5 years
|
Tamoxifen Citrate 20Mg Tab
|
Placebo Comparator: Placebo
Placebo 20 mg/day for 5 years
|
Placebo 20Mg Tab
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Jack Cuzick, PhD, Queen Mary University of London
Publications and helpful links
General Publications
- Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst. 2011 May 4;103(9):744-52. doi: 10.1093/jnci/djr079. Epub 2011 Apr 11.
- Stone J, Warren RM, Pinney E, Warwick J, Cuzick J. Determinants of percentage and area measures of mammographic density. Am J Epidemiol. 2009 Dec 15;170(12):1571-8. doi: 10.1093/aje/kwp313. Epub 2009 Nov 12.
- Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A; International Breast Cancer Intervention Study I Investigators. Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst. 2007 Feb 21;99(4):272-82. doi: 10.1093/jnci/djk049.
- Sestak I, Kealy R, Edwards R, Forbes J, Cuzick J. Influence of hormone replacement therapy on tamoxifen-induced vasomotor symptoms. J Clin Oncol. 2006 Aug 20;24(24):3991-6. doi: 10.1200/JCO.2005.04.3745.
- Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW. Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004 Apr 21;96(8):621-8. doi: 10.1093/jnci/djh106.
- Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T; IBIS investigators. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet. 2002 Sep 14;360(9336):817-24. doi: 10.1016/s0140-6736(02)09962-2.
- Warwick J, Pinney E, Warren RM, Duffy SW, Howell A, Wilson M, Cuzick J. Breast density and breast cancer risk factors in a high-risk population. Breast. 2003 Feb;12(1):10-6. doi: 10.1016/s0960-9776(02)00212-6.
- Sestak I, Kealy R, Nikoloff M, Fontecha M, Forbes JF, Howell A, Cuzick J. Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial. Br J Cancer. 2012 Jul 10;107(2):230-3. doi: 10.1038/bjc.2012.278. Epub 2012 Jun 26.
- Palva T, Ranta H, Koivisto AM, Pylkkanen L, Cuzick J, Holli K. A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo - a substudy for IBIS I Breast Cancer Prevention Trial. Eur J Cancer. 2013 Jan;49(1):45-51. doi: 10.1016/j.ejca.2012.06.015. Epub 2012 Jul 23.
- Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF; IBIS-I Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015 Jan;16(1):67-75. doi: 10.1016/S1470-2045(14)71171-4. Epub 2014 Dec 11.
- Brentnall AR, Cuzick J, Byers H, Segal C, Reuter C, Detre S, Sestak I, Howell A, Powles TJ, Newman WG, Dowsett M. Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials. Breast Cancer Res Treat. 2016 Aug;158(3):591-6. doi: 10.1007/s10549-016-3885-x. Epub 2016 Jul 11.
- Cuzick J, Brentnall AR, Segal C, Byers H, Reuter C, Detre S, Lopez-Knowles E, Sestak I, Howell A, Powles TJ, Newman WG, Dowsett M. Impact of a Panel of 88 Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk Women: Results From Two Randomized Tamoxifen Prevention Trials. J Clin Oncol. 2017 Mar;35(7):743-750. doi: 10.1200/JCO.2016.69.8944. Epub 2016 Dec 28.
- Smith SG, Sestak I, Howell A, Forbes J, Cuzick J. Participant-Reported Symptoms and Their Effect on Long-Term Adherence in the International Breast Cancer Intervention Study I (IBIS I). J Clin Oncol. 2017 Aug 10;35(23):2666-2673. doi: 10.1200/JCO.2016.71.7439. Epub 2017 Jun 29. Erratum In: J Clin Oncol. 2018 Jan 20;36(3):304.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Bone Density Conservation Agents
- Estrogen Antagonists
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Tamoxifen
Other Study ID Numbers
- CDR0000064151
- 2005-003091-38 (EudraCT Number)
- ISRCTN91879928 (Registry Identifier: ISRCTN)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
Clinical Trials on Tamoxifen Citrate 20Mg Tab
-
Virginia Commonwealth UniversityWithdrawnVaginal BleedingUnited States
-
Keun-Sik HongSamsung Medical Center; Seoul St. Mary's Hospital; Seoul National University... and other collaboratorsUnknownStroke, IschemicKorea, Republic of
-
Yooyoung Pharmaceutical Co., Ltd.Completed
-
Sharif Medical Research CenterRecruitingMale Infertility | OligoasthenoteratozoospermiaPakistan
-
Seoul National University HospitalActive, not recruitingHormone Receptor-positive Breast Cancer | Premenopausal Breast CancerKorea, Republic of
-
HK inno.N CorporationCompletedHealthy Male SubjectsKorea, Republic of
-
Sohag UniversityNot yet recruitingDiffuse Large B Cell Lymphoma
-
Assiut UniversityCompleted
-
HK inno.N CorporationCompletedHealthyKorea, Republic of
-
University of NebraskaNot yet recruitingPancreatic Cyst | Pancreatic Mucinous Cystic NeoplasmUnited States