Anastrozole versus placebo in post-menopausal women at increased risk of breast cancer

Phase 3

Completed

• Conditions: Breast cancer; Cancer

• Registration Number: ISRCTN31488319
• Lead Sponsor: Queen Mary University of London (UK)

Brief Summary

2003 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/12903846 protocol 2008 Results article in https://www.ncbi.nlm.nih.gov/pubmed/18768369 cognition substudy results 2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/24333009 results 2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/25456365 substudy results 2018 Results article in https://www.ncbi.nlm.nih.gov/pubmed/29126161 adherence results 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33656637/ results (added 04/03/2021) 2019 Results article in https://pubmed.ncbi.nlm.nih.gov/31839281/ long-term results (added 06/10/2021) 2023 Other publications in https://pubmed.ncbi.nlm.nih.gov/38070530/ Results of case control study of IBIS-II participants measuring serum hormone levels (added 11/12/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2005-04-26
• Study Completion: 2021-05-31
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 3864

Inclusion Criteria

All women must be post-menopausal and between the ages of 40 to 70.
Postmenopausal status is defined as meeting one or more of the following criteria:
1. Over the age of 60 years
2. Bilateral oophorectomy
3. Aged 60 or under with a uterus and amenorrhoea for at least 12 months
4. Aged 60 or under without a uterus and with Follicle-Stimulating Hormone (FSH) more than 30 IU/L

The entry criteria will be age-dependent to reflect the increasing baseline risk with age.

Aged 45 to 70 - the entry criteria are based on a relative risk of at least twofold and are similar to IBIS-I. At least one of the following must be satisfied:
1. First degree relative who developed breast cancer at age 50 or less
2. First degree relative who developed bilateral breast cancer
3. Two or more first or second degree relatives who developed breast or ovarian cancer
4. Nulliparous (or first birth at age 30 or above) and a first degree relative who developed breast cancer
5. Benign biopsy with proliferative disease and a first degree relative who developed breast cancer
6. Mammographic opacity covering at least 50% of the breast in absence of Hormone Replacement Therapy (HRT) use within the last 3 months

Also aged 60 to 70 - because of their higher baseline risk, women aged 60 to 70 can enter the study with a smaller relative risk:
7. First degree relative with breast cancer at any age
8. Age at menopause 55 years or older
9. Nulliparous or age at first birth 30 years or above

Aged 40 to 44 - who are postmenopausal (usually because of a bilateral oophorectomy) are eligible if they satisfy one or more of the following criteria (approximately fourfold risk or greater):
10. Two or more first or second degree relatives who developed breast or ovarian cancer at age 50 or less
11. First degree relative with bilateral breast cancer who developed the first breast cancer at age 50 or less
12. Nulliparous (or first birth at age 30 or above) and a first degree relative who developed breast cancer at age 40 or less
13. Benign biopsy with proliferative disease and a first degree relative who developed breast cancer at age 40 or less

All age groups (40 to 70) - women who have had certain breast conditions will also be eligible. These are:
14. Lobular Carcinoma In Situ (LCIS)
15. Atypical ductal or lobular hyperplasia in a benign lesion
16. Ductal Carcinoma In Situ (DCIS), diagnosed within the last six months, and treated by mastectomy. Oestrogen Receptor (ER) or Progesterone Receptor (PgR) status of DCIS must be known, and must be greater than 5% positive cells.
17. Women with a ten year risk greater than 5%, who do not fit into the above categories (risk equivalent). All risk equivalent women must be approved by the Steering Committee Co-Chairman (London IBIS central office). These women must have clearly apparent family history and/or other risk factors indicating appropriate increased risk of breast cancer for their age. Particularly careful assessment of the risk-benefit for these women should be undertaken before a woman from this group is entered.

All women must have:
1. Had a mammogram taken within the last year and showing no evidence of breast cancer
2. Had a baseline bone mineral density scan within the last two years (dual-energy X-ray absorptiometry [DXA] either of hip, lumbar spine, forearm) and spinal X-ray
3. Signed a consent form after receiving full information about the study

Exclusion Criteria

Current exclusion criteria as of 23/02/2012
1. Still having periods
2. Have breast cancer, or have had breast cancer in the past (unless you have had DCIS - see criteria for specific age groups)
3. Have had any other cancer in the last five years (except non-melanoma skin cancer or carcinoma in situ of the cervix or Hodgkin's disease if before the age of 30 and treated with mantle therapy.
4. Have had tamoxifen, raloxifene or other Selective Estrogen Receptor Modulators (SERMs) for more than six months in the past 5 years. (women in IBIS-1 are eligible if they have been off the therapy for more than five years.
5. Want to carry on taking HRT that contains oestrogen
6. Have had (or are planning to have) your breast(s) removed (a mastectomy) to try and prevent breast cancer
7. Have any other serious medical conditions
8. have had treatment with non-approved experimental drugs during the 6 months before randomisation.
9. History of Lactose or gluten intolerance.
10. Life expectancy of less than 10 years or other medical condition which would significantly interfere with the ability to accept the trial treatment.

Previous exclusion criteria
1. Still having periods
2. Have breast cancer, or have had breast cancer in the past (unless you have had DCIS - see criteria for specific age groups)
3. Have had any other cancer in the last five years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
4. Have had tamoxifen, raloxifene or other Selective Estrogen Receptor Modulators (SERMs) for more than three months in the past
5. Have taken part in the IBIS 1 trial
6. Want to carry on taking HRT that contains oestrogen
7. Have had (or are planning to have) your breast(s) removed (a mastectomy) to try and prevent breast cancer
8. Have any other serious medical conditions
9. Have taken any other drug as part of a clinical trial within the last three months

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Breast cancer incidence

Secondary Outcome Measures

Name	Time	Method
Current secondary measures as of 23/02/2012:<br>1. Breast cancer mortality<br>2. Cardiovascular events <br>3. Osteoporosis <br>4. Other relevant side effects<br> <br>Previous secondary measure:<br>1. Breast cancer mortality<br>2. Thromboembolic events <br>3. Cardiovascular events <br>4. Osteoporosis <br>5. Other relevant side effects