Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial
- Study type
- Clinical trial
- Study name
- ATLAS
- Design
- International randomised trial with an open control group, 1:1 allocation by central computer using minimisation (registered as ISRCTN19652633)
- Sample size
- 12,894 women (6846 with ER-positive disease, 1248 ER-negative and 4800 ER-unknown)
- Source
- The Lancet · 2013
In plain words
This large study showed that women with oestrogen receptor-positive breast cancer who had taken tamoxifen for 5 years were less likely to have their cancer come back, and less likely to die of breast cancer, if they continued the medicine up to 10 years. This benefit was mostly seen after the tenth year. On the other hand, the risk of a blood clot in the lungs and of endometrial cancer (cancer of the lining of the womb) went up, although the risk of heart disease caused by narrowed arteries was lower. The decision to continue or stop the medicine should be made with the treating doctor, taking each patient's circumstances into account.
Key results
Treatment arms and regimens
Continuation of tamoxifen to 10 years (about 5 more years after 5 years of prior treatment); stopped only if a definite contraindication arose. The tamoxifen regimen before and during ATLAS was almost always Nolvadex 20 mg daily. Other aspects of treatment were at the discretion of the treating physician (3428 ER-positive women).
Immediate cessation of tamoxifen at 5 years (open control, no placebo); tamoxifen was restarted only if a definite indication arose (3418 ER-positive women).
Source of the regimen details: Full text of the paper (PMC3596060, Study design and Procedures sections)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women with early breast cancer (all detectable disease had been removed) who had taken tamoxifen for several years and were still taking it (or had stopped in the past year and could resume with little interruption), were clinically disease-free (local recurrence resected and no distant metastases), and for whom the patient and doctor were substantially uncertain whether to stop or continue for about 5 more years. There were no restrictions on age, type of surgery, histology, hormone receptor status, nodal status or other treatments. Enrolment took place from 36 countries or regions between 1996 and 2005; this report covers women who had received at least 4 years of tamoxifen (median 5 years; interquartile range 4.8 to 5.2). The analysis of breast cancer outcomes focused on 6846 women with ER-positive disease, and adverse events were examined in all 12,894 women (ER-positive, negative or unknown).
Endpoints
Breast cancer outcomes including recurrence, breast cancer mortality and overall mortality in women with ER-positive disease, plus adverse events (hospitalisation or death from specific conditions such as pulmonary embolism, stroke, ischaemic heart disease and endometrial cancer) in all women. Long-term follow-up continues.
Safety and side effects
In all 12,894 women, rate ratios (RR) for hospitalisation or death from specific conditions were: pulmonary embolism 1.87 (95% CI 1.13 to 3.07; p=0.01; including 0.2% mortality in both treatment groups), stroke 1.06 (0.83 to 1.36), ischaemic heart disease 0.76 (0.60 to 0.95; p=0.02) and endometrial cancer 1.74 (1.30 to 2.34; p=0.0002). The cumulative risk of endometrial cancer during years 5 to 14 was 3.1% (mortality 0.4%) in the continuation group versus 1.6% (mortality 0.2%) in the control group (absolute mortality increase 0.2%).
Clinical significance and place in guidelines
According to the abstract, continuing tamoxifen to 10 years in women with ER-positive disease reduces recurrence and mortality more than 5 years of treatment, and no effect was seen in ER-negative patients; it is therefore an option for longer adjuvant therapy in ER-positive patients. This benefit must be weighed against the increased risk of pulmonary embolism and endometrial cancer. The status of this approach in current clinical guidelines (for example considerations of menopausal status and patient risk) should be checked in up-to-date guideline sources and is not mentioned in the abstract.
Limitations
The control group was open (treatment not masked). The analysis of breast cancer outcomes focused only on ER-positive women, and ER status was unknown in 4800 women. The clear benefit was seen mainly after year 10, and long-term follow-up continues. Full subgroup results and dose details are not given in the abstract.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.