***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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    Input: Tamoxifen is associated with a reduced risk of coronary heart disease ( CHD ) . However , there are few reports on long-term effects . Using data from a large Swedish r and omized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer , we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment . A total of 4,150 patients were breast cancer recurrence-free after 2 years . Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry were used to define events of disease . Hazard ratios were estimated using Cox regression . Patients assigned to 5 years in comparison with 2 years of postoperative tamoxifen experienced a reduced incidence of CHD [ hazard ratio ( HR ) , 0.83 ; 95 % CI 0.70–1.00 ] , especially apparent during the active treatment period ( HR 0.65 ; 95 % CI 0.43–1.00 ) . The mortality from CHD was significantly reduced ( HR 0.72 ; 95 % CI 0.53–0.97 ) . During the active treatment , the morbidity of other heart diseases was also significantly reduced ( HR 0.40 ; 95 % CI 0.25–0.64 ) but not after treatment stopped ( HR 1.06 ; 95 % CI 0.87–1.30 ) . Similar results were seen for both heart failure and atrial fibrillation/flutter . As compared to 2 years of therapy , 5 years of postoperative tamoxifen therapy  prevents CHD as well as other heart diseases . The risk reduction is most apparent during the active treatment period , and later tends to diminish Abstract Objective : To determine any cardiac or vascular morbidity associated with long term treatment with tamoxifen given after mastectomy for primary breast cancer . Design : Cohort study using linkage between data base of a r and omised trial and statistics of Scottish hospital in patients to identify episodes of cardiac and vascular morbidity . Setting : NHS hospitals in Scotl and . Subjects : 1312 women who had undergone mastectomy for breast cancer and who were r and omised either to a treatment group to receive adjuvant tamoxifen or to a control group to be given tamoxifen only  on first relapse of disease . Maximum duration of tamoxifen treatment was 14 years . Total woman years of follow up were 9943 . Main outcome measures : R and omised and observational comparisons of risk ( expressed as hazard ratios ) of myocardial infa rct ion , other cardiac event , cerebrovascular disease , or thromboembolic event according to treatment allocated and between non-users , former users , and current users of tamoxifen . Results : Use of tamoxifen was associated with lower rates of myocardial infa rct ion . Hazard ratio for women in control group was 1.92 ( 95 % confidence interval 0.99 to 3.73 ) compared with women allocated to adjuvant treatment . The association was stronger for current use : hazard ratio for non-users was 3.49 ( 1.52 to 8.03 ) compared with current users . Current users of tamoxifen , however , had higher rates of thromboembolic events : hazard ratio for non-users was 0.40 ( 0.18 to 0.90 ) compared with current users . Conclusions : Our results provide further evidence that tamoxifen reduces the risk of myocardial infa rct ion . Thromboembolic events should be carefully monitored in trials of tamoxifen , particularly those of prophylactic treatment , in which tamoxifen is given to healthy women www.thelancet.com/oncology Vol 17 July 2016 e275 Postmenopausal women with hormone-receptor-positive early breast cancer could benefit by extending adjuvant therapy with aromatase inhibitors from 5 years to 10 years , a new double-blind , phase 3 , placebo-controlled trial study suggests . Paul Goss ( Massachusetts General Hospital Cancer Centre , MA , USA ) and colleagues ’ study enrolled postmenopausal women with primary breast cancer who had received 4·5 - 6·0 years of adjuvant therapy with an aromatase inhibitor , most of whom had previously been treated with tamoxifen and who were disease-free at the time of enrolment . 1918 patients were r and omly assigned to receive 25 mg letrozole or placebo daily for a further 5 years . At a median follow-up of 6·3 years , 67 ( 7 % ) of 959 patients in the letrozole group had disease recurrence or contralaleral breast cancer compared with 98 ( 10 % ) of 959 patients in the placebo group . 5-year disease-free survival ( the primary endpoint ) was 95 % ( 95 % CI 93–96 ) in the letrozole group and 91 % ( 89–93 ) in the placebo group , ( 0·66 hazard ratio [ 95 % CI 0·48–0·91 ] ; p=0·01 ) . 5-year overall survival was similar between groups : 93 % ( 95 % CI 92–95 ) with letrozole and 94 % ( 92–95 ) with placebo ( HR 0·97 , 95 % CI 0·73–1·28 ; p=0·83 ) . Except for bone-related toxic eff ects , which occurred more frequently in the letrozole group compared with the placebo group , the toxic eff ects were similar . Commenting on the study , Miguel Martin ( Hospital General Universitario Gregorio Maranon , Madrid , Spain ) , said that “ this [ study ] is very relevant clinical ly , is practice changing , and should be discussed with our patients as a new option , taking into consideration the pros ( reduction of contralateral breast cancers and local-regional and distant metastases ) and the cons ( lack of survival benefi t and negative bone eff ects of letrozole ) of the therapy . ” He continued , “ Avoiding a contralateral breast cancer , regardless of the lack of benefit on survival , is a goal by itself . ” Goss told The Lancet Oncology , “ We are conducting deeper analyses to determine which patients should or should not continue [ alignment therapy ] . We have reduced recurrences or occurrences by 34 % which is clinical ly very significant . ” However , he concluded , “ Extending a therapy clinical ly for 5 years is important and my opinion is that ... a sober judgment by properly appointed guideline committees is needed ” before such changes are instituted Introduction Extended adjuvant endocrine therapy for breast cancer with aromatase inhibitors may potentially alter the lipid profile of postmenopausal patients and thus increase the risk of developing cardiovascular disease . In this study , a sub protocol of the ATENA ( Adjuvant post-Tamoxifen Exemestane versus Nothing Applied ) trial , we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal patients with operable breast cancer , in the adjuvant setting , with that of observation alone after completion of 5 to 7 years of primary treatment with tamoxifen . Methods In this open-label , r and omized , parallel-group study , 411 postmenopausal patients with operable breast cancer , who had been treated with tamoxifen for 5 to 7 years , were r and omized to either 5 additional years of exemestane ( 25 mg/day ; n = 211 ) or observation only ( n = 200 ) . Assessment s of total cholesterol ( TC ) , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and total serum triglycerides ( TRG ) were performed at baseline and then during each follow-up visit , performed at either 6 or 12 months , according to the center 's clinical practice , until completing 24 months in the study . Results TC and LDL levels increased significantly across time for both arms ; TC increase was more pronounced for the observation arm , and that was sustained up to 24 months . HDL levels decreased significantly across time for the exemestane arm , whereas no significant change was detected across time for the observation arm . Triglyceride levels decreased significantly across time on both arms , with no difference detected in changes from baseline between the exemestane and the observation arms . Conclusions Exemestane lacks the beneficial effect of tamoxifen on lipids ; however , sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm . Trial Registration Clinical Trials.gov ID : NCT00810706 PURPOSE This study analyzes the long-term results and causes of death in elderly women with node-positive breast cancer who participated in a double-blind adjuvant trial that compared tamoxifen with placebo to determine the benefit of 2 years of treatment . PATIENTS AND METHODS One hundred eighty-one women 65 to 84 years old were given 20 mg of tamoxifen or placebo daily for 2 years after stratification by estrogen receptor status , tumor size , and degree of lymph node involvement . Approximately 30 % of patients were older than 70 years and 20 % were older than 75 years . Eighty-five percent were estrogen receptor-positive . Median follow-up was 10 years . RESULTS Among the 168 eligible patients , there have been 98 recurrences ( 59 placebo v 39 tamoxifen ) , with reduced distant and bone-only first sites in patients treated with tamoxifen .  Median time to failure was 4.4 years for placebo versus 7.4 years for tamoxifen ( log-rank P = .001 ) . A similar number of new nonbreast cancers occurred in each arm ( seven placebo v six tamoxifen ) , but a reduced number of opposite-breast cancers ( five placebo v one tamoxifen ) was noted . Overall , there were 102 deaths ( 57 placebo v 45 tamoxifen ) . Median survivals were 8.0 years with placebo and 8.5 years with tamoxifen ( log-rank P = .063 ) ; 50 % of the tamoxifen patients and 33 % of the placebo patients are still alive . Sixty-one percent of the deaths were reported to have been caused by breast cancer recurrence , 4 % by other cancers , and 22 % by the sequelae of non-cancer-related illness , with equal distributions for cardiovascular and cerebrovascular disease . There was no increase in the number of endometrial or other types of cancer , or thrombotic or orthopedic complications in this older group . CONCLUSION Tamoxifen currently is the treatment of choice for elderly women with breast cancer . It extends the time to treatment failure by 3 years and reduces the number of recurrences , deaths , distant and bone-only first recurrences , and second breast cancers BACKGROUND Adjuvant tamoxifen therapy for breast cancer has been given for a period of several years . Cardiovascular diseases increased in incidence rapidly in women older than 60 years . Favorable changes in cardiovascular risk factors have been seen with 2 years of tamoxifen therapy , and lower rates of myocardial infa rct ion and of hospitalization for heart disease have been observed in tamoxifen-treated women . PURPOSE We sought to evaluate changes in risk factors for cardiovascular diseases in postmenopausal women after therapy with tamoxifen for 5 years . METHODS Five years after their initial entry in a 2-year r and omized , placebo-controlled toxicity study , we re-examined 62 of the original 140 disease-free , axillary node-negative postmenopausal breast cancer patients . These 62 patients were women available for study because they had not suffered major illness and had continued on either the tamoxifen or no-tamoxifen regimen to which they had been originally r and omly assigned for the entire 5 years . Patient and control blood sample s were analyzed for total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol and subfractions , triglycerides , apolipoprotein AI , apolipoprotein B , lipoprotein(a ) , fibrinogen , glucose , and platelets . RESULTS At base line for all measurements except atherogenic lipoprotein [ lipoprotein(a ) ] , the 30 long-term tamoxifen recipients and the 32 long-term no-tamoxifen recipients were not significantly different . After 5 years , levels of total serum cholesterol ( P < .001 ) , LDL cholesterol ( P < .001 ) , and lipoprotein(a ) ( P = .001 ) were significantly lower , and apolipoprotein AI levels were significantly higher ( P < .001 ) in the tamoxifen-treated group compared with the no-tamoxifen group . Apolipoprotein B levels increased to a greater extent in the no-tamoxifen than in the tamoxifen group ( P < .001 ) . After 5 years , fibrinogen level decrease and triglyceride level increases in the tamoxifen group compared with the no-tamoxifen group were of borderline statistical significance and HDL cholesterol levels were not different in the two groups . CONCLUSION Favorable changes in lipid , lipoprotein , and fibrinogen levels seen early in tamoxifen therapy in postmenopausal women persist with treatment of 5 years . IMPLICATION S The types and magnitude of changes in cardiovascular risk factors seen here with tamoxifen are similar to a certain extent with those seen with estrogen supplements . Further risk-factor and ethnic-group data are needed to estimate the magnitude of expected benefits of tamoxifen treatment on incidence of heart disease PURPO 
    Output:
    
Conclusions The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter .