***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Previously reported information from B-14 , a National Surgical Adjuvant Breast and Bowel Project ( NSABP ) r and omized , placebo-controlled clinical trial , demonstrated that patients with estrogen receptor (ER)-positive breast cancer and negative axillary lymph nodes experienced a prolonged benefit from 5 years of tamoxifen therapy . When these women were rer and omized to receive either placebo or more prolonged tamoxifen therapy , they obtained no additional advantage from tamoxifen through 4 years of follow-up . Because the optimal duration of tamoxifen administration continues to be controversial and because there have been 3 more years of follow-up and a substantial increase in the number of events since our last report , an up date of the B-14 study is appropriate . METHODS Patients ( n = 1172 ) who had completed 5 years of tamoxifen therapy and who were disease free were rer and omized to receive placebo ( n = 579 ) or tamoxifen ( n = 593 ) .  Survival , disease-free survival ( DFS ) , and relapse-free survival ( RFS ) were estimated by the Kaplan-Meier method ; the differences between the treatment groups were assessed by the log-rank test . Relative risks of failure ( with 95 % confidence intervals ) were determined by the Cox proportional hazards model . P values were two-sided . RESULTS Through 7 years after reassignment of tamoxifen-treated patients to either placebo or continued tamoxifen therapy , a slight advantage was observed in patients who discontinued tamoxifen relative to those who continued to receive it : DFS = 82 % versus 78 % ( P = .03 ) , RFS = 94 % versus 92 % ( P = .13 ) , and survival = 94 % versus 91 % ( P = .07 ) , respectively . The lack of benefit from additional tamoxifen therapy was independent of age or other characteristics . CONCLUSION Through 7 years of follow-up after rer and omization , there continues to be no additional benefit from tamoxifen administered beyond 5 years in women with ER-positive breast cancer and negative axillary lymph nodes Several reports have noted an association between the use of tamoxifen in breast cancer patients and the subsequent development of endometrial carcinoma . Magriples et al. ( J. Clin . Oncol . 11 , 485 - 490 , 1993 ) recently reported that 67 % of uterine cancers that developed in 15 breast cancer patients on tamoxifen  had high- grade lesions or high-risk histologies , compared to 24 % of those developing in 38 breast cancer patients not receiving tamoxifen .  To confirm these results , we conducted a retrospective review of 73 patients with a history of breast cancer who subsequently developed uterine cancer and underwent surgery at our institution . Twenty-three ( 32 % ) had received tamoxifen for at least 1 year , with a median duration of use of 4.5 years , while 50 ( 68 % ) did not receive tamoxifen . The median interval between diagnosis of breast and corpus cancer was less in the group that received tamoxifen than in the group that did not ( 4.6 vs 6.7 years ) , but this was not statistically significant . Seventy-four percent of the corpus cancers in the tamoxifen group were adenocarcinomas , while 26 % were considered high-risk histologies , which was identical to the findings for the group that did not receive tamoxifen . The distribution by FIGO stage was I , 15 ( 65 % ) ; II , 2 ( 9 % ) ; III , 5 ( 22 % ) ; and IV , 1 ( 4 % ) for the tamoxifen group , and I , 37 ( 74 % ) ; II , 1 ( 2 % ) ; III , 8 ( 16 % ) ; IV , 3 ( 6 % ) ; and unstaged , 1 ( 2 % ) for the group not receiving tamoxifen ( P = NS ) . For patients with endometrial adenocarcinoma , 23 % of the tamoxifen group had grade 3 lesions , compared with 19 % of the no tamoxifen group ( P = NS ) . Our review of corpus cancers developing in breast cancer patients demonstrated no significant difference in stage , grade , or histologic subtype based on tamoxifen use BACKGROUND Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen  , further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence . We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor , anastrozole , for 3 years among women who had completed 5 years of adjuvant therapy . METHODS Austrian Breast and Colorectal Cancer Study Group ( ABCSG ) Trial 6a is an extension of ABCSG Trial 6 , in which hormone receptor-positive postmenopausal patients received 5 years of adjuvant tamoxifen , with or without the aromatase inhibitor aminoglutethimide , for the first 2 years of therapy . For ABCSG Trial 6a , patients who were disease free at the end of Trial 6 were r and omly assigned to receive either 3 years of anastrozole or no further treatment .  Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan-Meier curves , and tolerability data were estimated using logistic regression analysis with odds ratios and 95 % confidence intervals ( CIs ) . RESULTS ABCSG Trial 6a included 856 patients . At a median follow-up of 62.3 months , women who received anastrozole ( n = 387 ) had a statistically significantly reduced risk of recurrence ( locoregional recurrence , contralateral breast cancer , or distant metastasis ) compared with women who received no further treatment ( n = 469 ; hazard ratio = 0.62 ; 95 % CI = 0.40 to 0.96 , P = .031 ) . Anastrozole was well tolerated , and no unexpected adverse events were reported . CONCLUSIONS These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment . Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types 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 BACKGROUND The most widely accepted end point in r and omized cancer screening trials is disease-specific mortality . The validity of this end point , however , rests on the assumption that cause of death can be determined accurately . An alternative end point is all-cause mortality , which depends only on the accurate ascertainment of deaths and when they occur . We compared disease-specific and all-cause mortality in published r and omized cancer-screening trials to indirectly assess the validity of the disease-specific mortality end point . METHODS We examined all 12 published r and omized trials of cancer screening for which both end points were available ( seven of mammography , three of fecal occult blood detection , and two of chest x-ray screening for lung cancer ) . For each r and omized trial , we subtracted disease-specific mortality observed in the screened group from that observed in the control group and all-cause mortality in the screened group from that in the control group . We then compared the differences in these two mortality measures . RESULTS In five of the 12 trials , differences in the two mortality rates went in opposite directions , suggesting opposite effects of screening . In four of these five trials , disease-specific mortality was lower in the screened group than in the control group , whereas all-cause mortality was the same or higher . In two of the remaining seven trials , the mortality rate differences were in the same direction but their magnitudes were inconsistent ; i.e. , the difference in all-cause mortality exceeded the disease-specific mortality in the control group . Thus , results of seven of the 12 trials were inconsistent in their direction or magnitude . CONCLUSION Major inconsistencies were identified in disease-specific and all-cause mortality end points in r and omized cancer screening trials . Because all-cause mortality is not affected by bias in classifying the cause of death , it should be examined when interpreting the results of r and omized cancer-screening trials PURPOSE National Cancer Institute of Canada Clinical Trials Group trial MA.17 r and omly assigned 5,187 postmenopausal , hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo . At 30 months median follow-up , letrozole significantly improved disease-free survival ( DFS ) in all patients and overall survival ( OS ) in node-positive patients . Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17 , making it ideal to explore the benefits , toxicities , and quality of life ( QOL ) impact of letrozole on older women . PATIENTS AND METHODS In this study , 5,169 r and omly assigned patients were divided into three age groups : younger than 60 years ( n = 2,152 ) , 60 to 69 years ( n = 1,694 ) , and > or= 70 years ( n = 1,323 ) . Log-rank test was used to compare differences in DFS , distant-disease-free survival , and OS between age and treatment groups , and Cox models were used to estimate hazard ratios and associated 95 % CIs . QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality -of- 
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There was no apparent difference in the effect between pre- and post-menopausal patients .
In unselected patients , extended adjuvant tamoxifen is not associated with a significant reduction in recurrence , or a reduction in all-cause death .
Patients with lymph node positive breast cancer may derive some benefit .
Reduction in the risk of recurrence appears to occur only after completion of extended adjuvant therapy