Tamoxifen for the Prevention of Breast Cancer in High-Risk Women

NCT00002644 | Completed Phase 3

• 3 other identifiers: CDR00000641512005-003091-38ISRCTN91879928
• Study Type: interventional
• Target: 7,154
• Locations: 1 country
• Sites: 1

Brief Summary

The International Breast Cancer Intervention Study I (IBIS-I) was designed to investigate the use of tamoxifen in preventing breast cancer in women with a higher risk of developing the disease. Recruitment of women to IBIS-I ended in March 2001 and it recruited 7154 women from 36 centres in 9 countries. The results of the study showed that tamoxifen reduced the incidence of breast cancer by one third in these high risk women but with some serious side effects. IBIS-II was designed to continue the work started in IBIS-I by examining the role of anastrozole in the prevention of breast cancer which we hope will reduce breast cancer by even more than tamoxifen with less serious side effects.

Conditions

Breast Cancer

Keywords

breast cancer; tamoxifen; prevention; IBIS

Study Arms (2)

Tamoxifen citrate

EXPERIMENTAL

Tamoxifen citrate 20 mg/day for 5 years

Drug: Tamoxifen Citrate 20Mg Tab

Placebo

PLACEBO COMPARATOR

Placebo 20 mg/day for 5 years

Other: Placebo

Interventions

Tamoxifen Citrate 20Mg Tab DRUG

Tamoxifen Citrate 20Mg Tab

Tamoxifen citrate

Placebo OTHER

Placebo 20Mg Tab

Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• )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)\*

You may not qualify if:

• 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.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

Queen Mary University of London

London, England, EC1M6BQ, United Kingdom

Location

Related Publications (13)

• 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.

  PMID: 21483019 RESULT

• 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.

  PMID: 19910376 RESULT

• 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.

  PMID: 17312304 RESULT

• 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.

  PMID: 16921052 RESULT

• 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.

  PMID: 15100340 RESULT

• 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.

  PMID: 12243915 RESULT

• 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.

  PMID: 14659350 RESULT

• 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.

  PMID: 22735900 RESULT

• 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.

  PMID: 22832202 RESULT

• 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.

  PMID: 25497694 RESULT

• 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.

  PMID: 27400912 RESULT

• 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.

  PMID: 28029312 RESULT

• 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.

  PMID: 28661758 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Jack Cuzick, PhD

  Queen Mary University of London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: May 11, 2004
• Study Start: January 1, 1994
• Primary Completion: January 1, 2001
• Study Completion: March 30, 2011
• Last Updated: December 11, 2024

Record last verified: 2024-12

Locations

GB (1)