SummaryBackgroundFor 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.MethodsIn 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.FindingsAmong 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%).InterpretationFor women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurren...

Graphical abstract

ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP4+4 did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD8, treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.

Background We investigated associations between tobacco exposure, history of schistosomiasis and bladder cancer risk in Egypt. Methods We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression we estimated the covariate-adjusted odds ratios (OR) and 95% confidence interval (CI) of the associations. Results Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (UC) (OR = 1.8, 95% CI = 1.4, 2.2), but not squamous cell carcinoma (SCC); smoking both waterpipes and cigarettes was associated with an even greater risk for UC (OR = 2.9, 95% CI = 2.1, 3.9) and a statistically significant risk for SCC (OR = 1.8, 95% CI = 1.2, 2.6). Among non-smoking men and women, to environmental tobacco smoke exposure was associated with an increased risk of UC. History of schistosomiasis was associated with increased risk of both UC (OR = 1.9, 95% CI = 1.2, 2.9) and SCC (OR = 1.9, 95% CI = 1.2, 3.0) in women and to a lesser extent (OR = 1.4, 95% CI = 1.2, 1.7 and OR = 1.4, 95% CI = 1.1, 1.7, for UC and SCC respectively) in men. Conclusions The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and UC. Impact This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis, and suggests that smoking both cigarettes and waterpipes increases the risk for SCC and UC in Egyptian men.