ATLAS: Adjunct Tamoxifen – Longer against shorter (Breast Cancer and Tamoxifen Duration – 5 years versus 10 years
RECRUITMENT IS CLOSED
Principal Investigator: Professor Susan Davis
Associate Investigators: Dr Peter Gregory, Dr Ian Haines, Ms Jo Bradbury
ATLAS is an international, multi-centred study which was designed to evaluate the effects of greater than 5 years of tamoxifen versus cessation of therapy after about 5 years on total mortality in women with breast cancer. ATLAS is coordinated in Australia & New Zealand by the ANZ Breast Cancer Trials Group (ANZBCTG).
Recruitment to ATLAS commenced in 1996 and closed in March 2005.
The conception of ATLAS: Approximately 1 million women worldwide are being treated with tamoxifen following breast cancer (35,000 women in Australia).We know that with 5 years of tamoxifen the benefits are 30 times greater than the risks. So the current tendency is for adjuvant tamoxifen to be used for about 5 years in women following initial treatment for breast cancer. But there is uncertainty as to whether longer use would be more beneficial.
There are potential, serious adverse side effects of tamoxifen, which are:
- endometrial hyperplasia / polyps / cancer
- venous thromboembolic events.
There is insufficient, reliable data on the balance of the risk of these side effects and the net survival benefit with the longer treatment with tamoxifen. ATLAS will provide this data.
The establishing of ATLAS
ATLAS was set up as a ‘mega trial' based on ISIS (International Studies of Infarct Survival). The ISIS Collaborative Group of over 1000 hospitals worldwide randomised more than 100,000 myocardial infarction patients into their studies within just a few years. This was achieved by:
- addressing important therapeutic questions,
- basing eligibility on uncertainty of both the physician and the patient,
- streamlining the trial design,
- adopting very simple protocols.
Aim of ATLAS
(Therapeutic question): To establish whether the more prolonged treatment with tamoxifen carries a net therapeutic advantage in terms of recurrence free survival and/or overall survival compared with treatment for 5 years in women with breast cancer.
Patient Cohort (eligibility)
Is totally comprised of women who, with their doctors, were uncertain as to whether to prolong their tamoxifen treatment beyond 5 years.
ATLAS trial design
The ATLAS Study was designed to establish whether there is an improvement in recurrence free survival and/or survival with tamoxifen beyond the current treatment time of 5 years.A reliable demonstration of just a small benefit with the prolonged use of tamoxifen could save the lives of thousands of women worldwide. ATLAS will detect a difference of 2-3% in survival between the treatment group (those women who were randomly allocated to stay on tamoxifen following about 5 years of treatment) and the control group (those who were randomly allocated to stop tamoxifen).
The principal analysis will be of all cause mortality, which will be complemented by subsidiary analyses of death from specific causes, eg breast cancer, myocardial infarction. The analysis will be stratified by age, oestrogen receptor status and other prognostic factors recorded at the enrolment of the women. It will be an ‘intention to treat' analysis, which means that it will detect any real difference between the trial arms in their effects on long term outcome.
ATLAS will determine the balance of risks versus benefits of greater than 5 years of tamoxifen through direct randomised comparison. Data will be collected on serious, unexpected side effects, which are considered attributable to tamoxifen, including vascular events and secondary primary cancers thereby contributing to the growing body of evidence on the longer-term side effects, both negative and positive, of tamoxifen.
ATLAS FOLLOW-UP PHASE: ATLAS randomised some 15,000 women. In combination with aTTom (adjuvant Tamoxifen Treatment on mortality, the UK counterpart to ATLAS) and 3 other smaller trials that had already published their data, there were about 20,000 women, in total, with ER+/? Disease. So the ATLAS Trial Steering Committee endorsed the recruitment closure in 2005.
Long-term follow up in research studies, such as ATLAS, is imperative.The compliance of participants with the original, randomly-assigned treatment allocation was encouraged for the full duration of follow-up to protect the scientific integrity of ATLAS and the data collected on each woman.
The ATLAS Study 5 year follow-up phase concluded in 2010. At this time the organisers of ATLAS in Oxford, UK, requested that ATLAS move into an extended follow-up period, which will conclude in early 2015. This will be of great importance in reliably assessing the longer-term effects of tamoxifen on recurrence and the net effects, if any, on mortality.
To see the latest results for this study please click here.