The starting point to do a trial well is to identify an important question to address. So much better, if this question emerges from a meta-analysis of the existing evidence as was the case with the ATLAS trial. The Early Breast Cancer Trialists Collaborative Group identified a number of small trials comparing 10 years treatment with tamoxifen with 5 years, but these early trials were too small to reliably assess the effects of longer treatment.
ATLAS recruited patients from 36 countries or regions during 1996-2005 enrolling a total of 12,894 women of whom 6,846 had oestrogen receptor-positive disease. Annual follow up was achieved without the need for extra visits or investigations and was similar in both groups.
The main analysis showed that allocation to 10 years treatment with tamoxifen reduced both recurrence of breast cancer (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls; RR 0·84, 95% CI 0·76–0·94; p=0·002), reduced breast cancer mortality (331 deaths with recurrence in women allocated to continue vs 397 in controls, p=0·01) and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The importance of prolonged follow-up in the trial is highlighted by the fact that the main effects on recurrence and breast cancer mortality only became apparent during the second decade after diagnosis.
Although known side-effects were increased (at least in postmenopausal women) by longer treatment, the absolute reduction in breast cancer mortality was an order of magnitude greater than the absolute increase in mortality due to these side-effects. Taken together with the results from trials of 5 years of tamoxifen versus none, the results from ATLAS show that 10 years of effective endocrine therapy can approximately halve breast cancer mortality during years 10–14 after diagnosis.
In conclusion, the ATLAS trial identified an important unanswered question and reliably addressed it using a simple randomised study design with prolonged follow-up of a large number of women with oestrogen receptor-positive breast cancer.
You can read the paper here.