For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Despite the increasing number of manuals on how to develop clinical practice guidelines (CPGs) there remain concerns about their quality. The aim of this study was to review the quality of CPGs across a wide range of healthcare topics published since 1980. The authors conducted a literature search in MEDLINE to identify publications assessing the quality of CPGs with the Appraisal of Guidelines, Research and Evaluation (AGREE) instrument. For the included guidelines in each study, the authors gathered data about the year of publication, institution, country, healthcare topic, AGREE score per domain and overall assessment. In total, 42 reviews were selected, including a total of 626 guidelines, published between 1980 and 2007, with a median of 25 CPGs. The mean scores were acceptable for the domain 'Scope and purpose' (64%; 95% CI 61.9 to 66.4) and 'Clarity and presentation' (60%; 95% CI 57.9 to 61.9), moderate for domain 'Rigour of development' (43%; 95% CI 41.0 to 45.2), and low for the other domains ('Stakeholder involvement' 35%; 95% CI 33.9 to 37.5, 'Editorial independence' 30%; 95% CI 27.9 to 32.3, and 'Applicability' 22%; 95% CI 20.4 to 23.9). From those guidelines that included an overall assessment, 62% (168/270) were recommended or recommended with provisos. There was a significant improvement over time for all domains, except for 'Editorial independence.' This review shows that despite some increase in quality of CPGs over time, the quality scores as measured with the AGREE Instrument have remained moderate to low over the last two decades. This finding urges guideline developers to continue improving the quality of their products. International collaboration could help increasing the efficiency of the process.