Results of the IBIS II suite of trials

4 October 2021

The IBIS-II suite of trials was unified in the goal of preventing breast cancer in women who were at higher than average risk of developing breast cancer due to family history and/or previous breast abnormalities. These trials were: – IBIS-II prevention: a randomised comparison of anastrozole to placebo in women without a history of breast cancer or ductal carcinoma in situ (DCIS); – IBIS-II DCIS: a randomised comparison of anastrozole to tamoxifen in women with a history of treated DCIS; – IBIS-II bone substudy: a randomised comparison of risedronate to placebo to examine the impact on bone density.

Internationally, 3864 women participated in the prevention trial (818 in Australia and New Zealand[ANZ]), 2980 in DCIS (178 ANZ), and 1410 in the bone substudy (229 ANZ). This trial opened in ANZ in 2005, and during the subsequent 16 years until now, an enormous amount has been learnt. Here only the main findings will be summarised:

  • Anastrozole, taken for 5 years, reduces the chance of developing breast cancer by 54% and DCIS by 59%, and continues to reduce the chance of these events for at least 5 years after completing anastrozole treatment.
  • In women who have had treatment for DCIS, anastrozole and tamoxifen were both similarly effective in preventing recurrence of DCIS, or occurrence of invasive breast cancer. There was also an ongoing protective effect after stopping. Side effects were different between the two treatments and may influence treatment choice.
  • In women taking anastrozole, who are at risk of low bone density, risedronate reduced the chance of anastrozole-related loss of bone density in the spine, but not in the hip. After stopping anastrozole and risedronate, bone density improved in the lumbar spine and stabilised in the hip in patients allocated to receive risedronate.

The main side effects seen with anastrozole were similar to those seen in other clinical trials and in routine practice: menopausal symptoms, arthritis/stiffness, and fractures. In the DCIS group, tamoxifen was associated with menopausal symptoms, deep vein thrombosis (uncommon), muscle spasm, and gynaecological changes. Overall, the treatments were well tolerated.

As a result of this trial, women at higher than average risk of developing breast cancer now have an additional effective option to reduce their risk. Women with treated DCIS can consider the use of either anastrozole or tamoxifen to prevent future breast cancer or DCIS. Clinical practice has changed worldwide leading to benefits flowing on to patients in the clinic. Further analyses are expected from the data that has already been collected.

Conference presentations and main publications:

The learnings from IBIS-II have been presented at multiple major international conferences and published in well-respected high impact medical journals. A selection of important trial publication references are listed below: Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Cuzick J, Sestak I, Forbes JF, Dowsett M, Cawthorn S, Mansel RE, Loibl S, Bonanni B, Evans DG, Howell A, on behalf of the IBIS-II investigators. The Lancet. 2020; 395(10218):117-122, 6736(19)32955-1.

Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia. Sestak I, Blake GM, Patel R, Colemen RE, Cuzick J, Eastell R. Bone. 2019; 124:83-88,

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Forbes JF, Sestak I, Howell A, Bonanni B, Bundred N, Levy C, von Minckwitz G, Eiermann W, Neven P, Stierer M, Holcombe C, Coleman RE, Jones L, Ellis I, Cuzick J, on behalf of the IBIS-II investigators. The Lancet. 2016; 387(10021):866-873,