IBIS: International Breast Cancer Intervention Studies
The IBIS programme is a set of international clinical trials evaluating whether hormone‑modulating medicines can
prevent or reduce recurrence of early breast cancer in women at increased risk — and whether long-term use is safe. Over 14,000 women across many countries have participated. The findings have helped shape clinical guidance on breast cancer prevention and management. The programme is now in long-term follow up and includes IBIS-I, IBIS-II Prevention, IBIS-II DCIS, and Bone Sub-study described below.
IBIS‑I: An international multi‑centre study of tamoxifen versus placebo in women at increased risk of breast cancer
Sponsor: Queen Mary University of London (UK)
Funder(s): Imperial Cancer Research Fund; Cancer Research Campaign; Cancer Research UK
Chief Investigator: Prof Jack Cuzick, Wolfson Institute of Preventive Medicine, Queen Mary University of London.
Registration: https://clinicaltrials.gov/study/NCT00002644
Recruitment start-end date: 14 April 1992 - 30 March 2011
Status: Completed (treatment finished, long‑term follow‑up ongoing)
Participants: 7,152 women (aged 35–70), of whom 4,277 were UK participants
About the Study:
IBIS‑I enrolled women at increased risk of breast cancer (mainly based on family history). Participants were randomized to receive daily tamoxifen (20 mg) or placebo for five years. The trial was double‑blind; neither participants nor doctors knew the assignment. During treatment, participants had regular check‑ups, mammograms, and some gave blood samples for cholesterol testing and future research. After the treatment period, long-term follow-up has continued, including annual questionnaires (UK) and national registry data collection to track breast cancer incidence, recurrences, side effects, and survival. For UK participants, ongoing data is obtained via NHS Digital registries; overseas participants are followed via registry systems where available.
Key Findings:
IBIS-I showed that tamoxifen significantly reduces the risk of breast cancer in women at increased risk, and that this protective effect continues long after treatment ends lasting for at least 20 years. A median follow‑up of 16 years showed that there was a 29–30% lower incidence in the tamoxifen group versus placebo. Although women taking tamoxifen experienced more side effects during treatment (gynaecological events, thromboembolism), these did not persist after the five-year treatment period. A significant reduction was observed for invasive oestrogen receptor–positive cancers and ductal carcinoma in situ (DCIS).
The results contributed to the NICE recommendation that tamoxifen can be offered to high-risk women to help prevent breast cancer.
IBIS-II
IBIS-II expanded on the findings of IBIS-I and included two separate trials:
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IBIS-II Prevention – for women at increased risk of breast cancer
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IBIS-II DCIS – for women treated for hormone-receptor positive DCIS (a pre-invasive breast cancer)
In addition, a large bone sub-study was carried out within IBIS-II Prevention.
IBIS‑II Prevention: An international multi‑centre study of anastrozole vs placebo in postmenopausal women at increased risk of breast cancer
Sponsor: Queen Mary University of London (UK)
Funder(s): Cancer Research UK; AstraZeneca
Chief Investigators: Prof Jack Cuzick, Prof John Forbes, Prof Anthony Howell
Registration: https://clinicaltrials.gov/study/NCT00078832
Recruitment start-end date: 2 February 2003 - 31 January 2012
Status: Treatment completed; long‑term follow-up ongoing- registry‑based for UK participants
Participants: 3,864 postmenopausal women (age 40–70) at increased risk of breast cancer
About the Study:
IBIS-II Prevention randomised postmenopausal women at increased risk to receive either anastrozole (1 mg daily) or a placebo, for five years. Women had regular clinic visits, mammograms, bone health scans, and provided blood/saliva samples during treatment. After the treatment period, participants were followed via clinic visits, phone calls, questionnaires and for UK participants, registry-based follow-up via NHS Digital since 2012.
Key Findings:
After an average of 10 years’ follow-up (median treatment period of 5 years), women taking anastrozole were 50% less likely to develop breast cancer than those taking placebo - making it a highly effective prevention option. Side effects such as joint aches, hot flushes and fractures were slightly more common during treatment, but no new side effects appeared after treatment ended.
In 2023, anastrozole was licensed by the MHRA as a preventive option for women at increased risk of breast cancer. In 2025, this licence was extended to several European countries including Germany, Ireland, Italy, France and others.
IBIS‑II Bone Sub‑study
Participants: 1,415 women (drawn from IBIS-II Prevention) - those randomised to anastrozole or placebo who underwent bone health assessment at baseline.
About the Sub‑study:
This sub-study was designed to evaluate the long-term effects of anastrozole on bone mineral density (BMD), the risk of osteoporosis and fractures, and whether bisphosphonate treatment could mitigate bone loss in women with low baseline BMD.
Participants had bone‑density scans (DXA) at baseline and follow‑up (e.g. at 3 years). Women with low bone density were offered bisphosphonate therapy to reduce fracture risk.
Significance:
This sub-study provides valuable safety data on bone health, helping to inform decisions about long-term aromatase inhibitor use in prevention - balancing cancer risk reduction with bone health.
IBIS‑II DCIS: An international multi‑centre trial of tamoxifen versus anastrozole in postmenopausal women with hormone-receptor positive Ductal Carcinoma In Situ (DCIS)
Sponsor: Queen Mary University of London (UK)
Funder(s): Cancer Research UK
Chief Investigators: Prof Jack Cuzick, Prof John Forbes, Prof Anthony Howell
Registration: https://clinicaltrials.gov/study/NCT00072462
Recruitment start-end date: 3 March 2003 - 8 February 2012
Status: Completed; long-term follow-up ongoing via observational registry study
Participants: 2,980 postmenopausal women (age 40–70) with hormone receptor–positive DCIS
About the Study:
IBIS-II DCIS enrolled women who had undergone surgery for DCIS (a non-invasive pre-cancer). Participants received either tamoxifen (20 mg/day) or anastrozole (1 mg/day) plus respective placebos for five years, in a double‑blind design. During treatment they had regular mammograms, bone scans, and provided biological samples. After treatment, long-term follow-up continues via clinic visits and national registries where available.
Key Findings:
IBIS-II DCIS showed no significant difference overall between tamoxifen and anastrozole in preventing recurrence of DCIS or progression to invasive breast cancer. During treatment, anastrozole offered slightly greater protection against hormone-receptor positive breast cancer, but this benefit did not persist after treatment stopped. Differences in side effect profiles were observed, giving clinicians and patients more choice, depending on individual risk factors and preferences.
Both drugs had similar levels of side effects, but the types of symptoms differed, giving clinicians more options depending on individual patient needs.
Future Results:
Further long-term data - including extended follow-up from IBIS-II (both Prevention and DCIS) under the observational study IBIS‑II-O (ISRCTN17443780) will be published here when available.
Withdrawals and Treatment‑Arm Requests:
If you took part in IBIS-I, IBIS-II Prevention, or IBIS-II DCIS and wish to withdraw consent for further follow-up data, or if you want to know which treatment arm you were allocated to, please contact: bartsctu-fup@qmul.ac.uk.
Participants will be notified by email or letter within 10 working days that their request to withdraw has been processed and they are no longer being followed up.