***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results . The overall evidence supports a reduction in the risk of breast cancer , but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear . METHODS We undertook a double-blind placebo-controlled r and omised trial of tamoxifen , 20 mg/day for 5 years , in 7152 women aged 35 - 70 years , who were at increased risk of breast cancer . The primary outcome measure was the frequency of breast cancer ( including ductal carcinoma in situ ) . Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography . FINDINGS After median follow-up of 50 months ( IQR 32 - 67 ) , 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group ( risk reduction 32 % [ 95 % CI 8 - 50 ] ; p=0.013 ) . Age , degree of risk , and use of hormone-replacement therapy did not affect the reduction . Endometrial cancer was non-significantly increased ( 11 vs 5 ; p=0.2 ) and thromboembolic events were significantly increased with tamoxifen ( 43 vs 17 ; odds ratio 2.5 [ 1.5 - 4.4 ] , p=0.001 ) , particularly after surgery . There was a significant excess of deaths from all causes in the tamoxifen group ( 25 vs 11 , p=0.028 ) . INTERPRETATION Prophylactic tamoxifen reduces the risk of breast cancer by about a third . Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation . Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease . The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen . The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear , and continued follow-up of the current trials is essential Meta-analytic investigations sometimes use assessment s of research quality according to a formal protocol as a tool for improving research synthesis . We asked whether a particular  quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference . In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled r and omized clinical trials comprising 107 primary studies , we found no relation between treatment difference and overall quality score . We also found no relation between quality score and variation in treatment difference . The level of quality scores has increased at a rate of 9 % per decade for three decades , averaging 0.51 on a scale of 0 to 1 for the 1980s , and leaving much room for improvement . Nevertheless , attention to quality of studies by editors , review ers , and authors may be raising both the level of research done and quality of the reports BACKGROUND The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention . To test this hypothesis , the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial ( P-1 ) in 1992 . METHODS Women ( N=13388 ) at increased risk for breast cancer because they 1 ) were 60 years of age or older , 2 ) were 35 - 59 years of age with a 5-year predicted risk for breast cancer of at least 1.66 % , or 3 ) had a history of lobular carcinoma in situ were r and omly assigned to receive placebo ( n=6707 ) or 20 mg/day tamoxifen  ( n=6681 ) for 5 years . Gail 's algorithm , based on a multivariate logistic regression model using combinations of risk factors , was used to estimate the probability ( risk ) of occurrence of breast cancer over time . RESULTS Tamoxifen reduced the risk of invasive breast cancer by 49 % ( two-sided P<.00001 ) , with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups , respectively . The decreased risk occurred in women aged 49 years or younger ( 44 % ) , 50 - 59 years ( 51 % ) , and 60 years or older ( 55 % ) ; risk was also reduced in women with a history of lobular carcinoma in situ ( 56 % ) or atypical hyperplasia ( 86 % ) and in those with any category of predicted 5-year risk . Tamoxifen reduced the risk of noninvasive breast cancer by 50 % ( two-sided P<.002 ) . Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69 % , but no difference in the occurrence of estrogen receptor-negative tumors was seen . Tamoxifen administration did not alter the average annual rate of ischemic heart disease ; however , a reduction in hip , radius ( Colles ' ) , and spine fractures was observed . The rate of endometrial cancer was increased in the tamoxifen group ( risk ratio = 2.53 ; 95 % confidence interval = 1.35 - 4.97 ) ; this increased risk occurred predominantly in women aged 50 years or older . All endometrial cancers in the tamoxifen group were stage I ( localized disease ) ; no endometrial cancer deaths have occurred in this group . No liver cancers or increase in colon , rectal , ovarian , or other tumors was observed in the tamoxifen group . The rates of stroke , pulmonary embolism , and deep-vein thrombosis were elevated in the tamoxifen group ; these events occurred more frequently in women aged 50 years or older . CONCLUSIONS Tamoxifen decreases the incidence of invasive and noninvasive breast cancer . Despite side effects result ing from administration of tamoxifen , its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease Summary Background 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 aim ed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years . Methods 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 r and omly 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 IS RCT N19652633 . Findings 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 % ) . Interpretation 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 . Funding Cancer Research UK , UK Medical Research Council , AstraZeneca UK , US Army , EU-Biomed Oesophageal and gastric adenocarcinoma share an unexplained male predominance , which would be explained by the hypothesis that oestrogens are protective in this respect . We carried out a nested case – control study of hormone replacement therapy ( HRT ) among 299 women with oesophageal cancer , 313 with gastric cancer , and 3191 r and omly selected control women , frequency matched by age and calendar year in the General Practitioners Research Data base in the United Kingdom . Data were adjusted for age , calendar year , tobacco smoking , alcohol consumption , body mass index , hysterectomy , and upper gastrointestinal disorders . Among 1 619 563 person-years of follow-up , more than 50 % reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers ( odds ratio ( OR ) , 0.48 , 95 % confidence interval ( CI ) 0.29–0.79 ) . This inverse association appeared to be stronger for gastric noncardia ( OR 0.34 , 95 % CI 0.14–0.78 ) and weaker for gastric cardia tumours ( OR 0.68 , 95 % CI 0.23–2.01 ) . There was no association between HRT and oesophageal adenocarcinoma ( OR 1.17 , 95 % CI 0.41–3.32 ) BACKGROUND Initial findings of the Italian R and omized Tamoxifen Prevention Trial found no reduction in risk of breast cancer with tamoxifen use , whereas the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial showed that tamoxifen treatment reduces risk of estrogen receptor-positive breast cancer . Here we present an extended follow-up of the Italian trial . METHODS From October 1 , 1992 , to December 31 , 1997 , 5408 otherwise healthy women who had undergone hysterectomy were r and omly assigned in a double-blind manner to tamoxifen ( 20 mg daily ) or placebo for 5 years . Rates of breast cancer and other events in the two groups were compared by the use of risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) . RESULTS After 11 years of follow-up , 136 women ( 74 placebo , 62 tamoxifen ) developed breast cancer ( RR = 0.84 , 95 % CI = 0.60 to 1.17 ; annual rates were 2.48 and 2.07 per 1000 women-years , respectively ) . The rates of breast cancer in the two study groups were similar among women who had had bilateral oophorectomy and among women at low risk for hormone receptor-positive ( HR+ ) disease but were much lower in the tamoxifen group among women at high risk ( placebo , 6.26 per 1000 women-years , tamoxifen , 1.50 per 1000 women-years ; RR = 0.24 , 95 % CI = 0.10 to 0.59 ) . During the treatment period , women in the tamoxifen group reported more hot flashes ( RR = 1.78 , 95 % CI = 1.57 to 2.00 ) , vaginal discharge ( RR = 3.44 , 
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Our meta- analysis results indicate that there was no substantial increase in gastric and colorectal cancer among the tamoxifen-treated female patients