An international study designed to answer reliably whether, for women who have hormone sensitive early breast cancer (the most common type of breast cancer), 10 years of adjuvant tamoxifen (a hormone treatment) confers more benefit than just 5 years in terms of reducing the risk of relapse and improving overall, long-term survival: Adjuvant Tamoxifen - Longer Against Shorter (ATLAS)

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN19652633
• Date of registration: 18/10/2012
• Prospective Registration: No
• Primary sponsor: University of Oxford (UK)
• Public title: An international study designed to answer reliably whether, for women who have hormone sensitive early breast cancer (the most common type of breast cancer), 10 years of adjuvant tamoxifen (a hormone treatment) confers more benefit than just 5 years in terms of reducing the risk of relapse and improving overall, long-term survival: Adjuvant Tamoxifen - Longer Against Shorter (ATLAS)
• Scientific title: An international randomised trial, involving tens of thousands of women, of 10 versus 5 years of adjuvant tamoxifen in the treatment of oestrogen receptor positive breast cancer, to assess the effects on relapse free and overall survival
• Date of first enrolment: 01/03/1995
• Target sample size: 15262
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN19652633
• Study type: Interventional
• Study design: International multicentre randomised controlled trial (Screening)
• Phase: Not Applicable

Countries of recruitment

Argentina, Australia, Belarus, Belgium, Brazil, Chile, China, Colombia, Croatia, Cuba, Czech Republic, Egypt, Estonia, France, Greece, Hong Kong, India, Iran, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Oman, Paraguay, Poland, Portugal, Russian Federation, South Africa, Spain, Taiwan, Tunisia, Turkey, United Kingdom, United States of America

Contacts

• Name: Christina Davies

Key inclusion & exclusion criteria

Inclusion criteria: Women were eligible for randomisation if:
1. They had had early breast cancer (in which, by definition, all detected disease could be removed surgically)
2. They had subsequently been on adjuvant tamoxifen for several years and were still on it (or had stopped only recently, and could therefore resume treatment without much interruption)
3. They still appeared clinically free of disease (with any local recurrence removed and no distant recurrence ever detected)
4. Long-term follow-up appeared practicable; and, fundamentally,
5. Substantial uncertainty was shared by the woman and her doctor about whether to stop tamoxifen or to continue for several more years, so compliance with random allocation to stop or to continue both seemed likely. There were no restrictions on age, type of initial surgery or histology, hormone receptor status, nodal status or what other treatments had also been given.
Exclusion criteria: Any perceived contraindications to continuing tamoxifen precluded entry. These were specified not by the ATLAS protocol but by the judgment of the responsible clinician. However, the protocol suggested as possible contraindications to tamoxifen continuation (and hence to trial entry):
1. Intended or actual pregnancy or breast feeding
2. Retinopathy
3. Need for coagulation therapy
4. Significant endometrial hyperplasia
5. Any other serious toxicity thought to be due to tamoxifen
6. Negligibly low risk of breast cancer death
7. Presence of another major life-threatening disease

Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Operable, oestrogen receptor positive breast cancer already trated with ~5 years of adjuvant tamoxifen
Cancer
Malignant neoplasm of breast

Intervention(s)

Random allocation was either to stop tamoxifen immediately, using no placebo tablets and restarting endocrine therapy only if a definite indication was thought to have emerged, or to continue tamoxifen for another 5 years (total 10 years), stopping before then, or changing to another endocrine therapy, only if a definite contra-indication was thought to have emerged. The tamoxifen regimen used both before and during the trial treatment period was almost always 20 mg/day oral Nolvadex. (In countries where continuing up to or beyond 5 years was not affordable for many patients, ATLAS supplied free Nolvadex to enable a woman to receive 5 years of tamoxifen prior to enrolment in ATLAS and for the full 5-year post-randomisation period.) All other aspects of patient management were at the doctor's discretion.

Primary Outcome(s)

1. Recurrence (loco-regional, contralateral or distant)
2. Breast cancer mortality

Secondary Outcome(s)

1. Overall mortality
2. Various first events before recurrence:
2.1. Cancer incidence (particularly uterine, including endometrial)
2.2. Hospital admissions for particular reasons (particularly uterine or vascular)
2.3. Cause-specific mortality

Secondary ID(s)

2004-000735-29

MHRA CTA: 21584/0002/001; EudraCT number: 2004-000735-29

NCT00003016

Source(s) of Monetary Support

Cancer Research UK, Medical Research Council (UK), AstraZeneca* (UK), US Army Breast Cancer Research Program (USA), EU-Biomed (EU), *AstraZeneca had no involvement in the scientific design or management of ATLAS, which is sponsored by the University of Oxford, the host organisation of the Clinical Trial Service Unit and Epidemiological Studies Unit (the international coordinating centre of ATLAS).