***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 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 PURPOSE In postmenopausal women with estrogen receptor-positive early breast cancer , surgery is usually followed by a 5-year course of tamoxifen . This report presents results of a prospect i ve , open-label , r and omized study , design ed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment , compared with continuing on tamoxifen for 5 years . PATIENTS AND METHODS After receiving tamoxifen treatment for 2 years , eligible patients ( n = 979 ) were r and omly assigned to switch to anastrozole ( 1 mg/d ) or continue tamoxifen ( 20 or 30 mg/d ) for an additional 3 years . Patients were monitored every 6 months during years 1 to 3 and annually thereafter . The primary efficacy variable was disease-free survival , including local or distant recurrence , new contralateral breast cancer , or death . Secondary variables were overall survival and assessment of safety . RESULTS Switching to anastrozole result ed in a significant reduction in the risk of disease recurrence ( hazard ratio [ HR ] , 0.66 ; 95 % CI , 0.44 to 1.00 ; P = .049 ) , and improved overall survival ( HR , 0.53 ; 95 % CI , 0.28 to 0.99 ; P = .045 ) compared with continuing on tamoxifen . Fewer patients who switched to anastrozole reported serious adverse events ( 22.7 % v 30.8 % ) compared with those who continued on tamoxifen , mainly due to more patients in the tamoxifen group with endometrial events . The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified . CONCLUSION Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen BACKGROUND Tamoxifen has been the mainstay of breast cancer therapy . Over time , resistance to tamoxifen may develop . The aromatase inhibitors have proven to be a powerful drug for use in hormone-sensitive early breast cancer . The switching strategy was design ed to combine the apparent superior efficacy of aromatase inhibitors with tamoxifen favourable effects . METHODS This study was performed on 120 postmenopausal women with histologically confirmed , hormone receptor-positive , operable invasive breast carcinoma who remained free of disease after 2 years of adjuvant tamoxifen therapy .  They were r and omized to receive either letrozole 2.5mg/day ( 60 patients ) or  to  continue 20mg/day tamoxifen for 5 years  ( 60 patients ) . RESULTS The treatment groups were well balanced in terms of age , tumor size , nodal status , oestrogen and progesterone receptor status , and previous surgery . The disease recurred in 10 patients in the group receiving tamoxifen and 3 patients in the same group switched to letrozole . There were 8 deaths in the group receiving tamoxifen and 3 deaths in the group of patients who switched to letrozole .  Disease-free survival was higher in the group of patients who switched to letrozole compared to the group of patients who received tamoxifen ( p=0.04 ) , while the overall survival was not statistically significantly different in the two groups . Letrozole was associated with a significantly lower rate of vaginal bleeding and thromboembolic events . However , bone fractures and adverse cardiovascular events were more frequent in the arm receiving letrozole than in the arm receiving tamoxifen but these differences were not statistically significant . CONCLUSION Switching to letrozole after 2 years of tamoxifen may be better than continuing five years of tamoxifen therapy as regard efficacy and tolerability . Further study is recomended on a larger group of patients to verify this finding . KEY WORDS Breast cancer - Hormonal treatment - Letrozole - Tamoxifen BACKGROUND Tamoxifen has been the st and ard adjuvant treatment for postmenopausal women with hormone-responsive early breast cancer for more than 20 years . However , the third-generation aromatase inhibitor anastrozole has proven efficacy and tolerability benefits compared with tamoxifen when used as initial adjuvant therapy . We investigate whether women who have received a period of adjuvant tamoxifen  would benefit from being switched to anastrozole . METHODS We present a combined analysis of data from two prospect i ve , multicentre , r and omised , open-label trials with nearly identical inclusion criteria . Postmenopausal women with hormone-sensitive early breast cancer who had completed 2 years ' adjuvant oral tamoxifen ( 20 or 30 mg daily ) were r and omised to receive 1 mg oral anastrozole ( n=1618 ) or 20 or 30 mg tamoxifen ( n=1606 ) daily for the remainder of their adjuvant therapy . The primary endpoint was event-free survival , with an event defined as local or distant metastasis , or contralateral breast cancer . Analysis was by intention to treat . FINDINGS 3224 patients were included in analyses . At a median follow-up of 28 months , we noted a 40 % decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group ( 67 events with anastrozole vs 110 with tamoxifen , hazard ratio 0.60 , 95 % CI 0.44 - 0.81 , p=0.0009 ) . Both study treatments were well tolerated . There were significantly more fractures ( p=0.015 ) and significantly fewer thromboses ( p=0.034 ) in patients treated with anastrozole than in those on tamoxifen . INTERPRETATION These data lend support to a switch from tamoxifen to anastrozole in patients who have completed 2 years ' adjuvant tamoxifen BACKGROUND Adjuvant therapy with an aromatase inhibitor improves outcomes , as compared with tamoxifen , in postmenopausal women with hormone-receptor-positive breast cancer . METHODS In two phase 3 trials , we r and omly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years . Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin , oophorectomy , or ovarian irradiation . The primary analysis combined data from 4690 patients in the two trials . RESULTS After a median follow-up of 68 months , disease-free survival at 5 years was 91.1 % in the exemestane-ovarian suppression group and 87.3 % in the tamoxifen-ovarian suppression group ( hazard ratio for disease recurrence , second invasive cancer , or death , 0.72 ; 95 % confidence interval [ CI ] , 0.60 to 0.85 ; P<0.001 ) . The rate of freedom from breast cancer at 5 years was 92.8 % in the exemestane-ovarian suppression group , as compared with 88.8 % in the tamoxifen-ovarian suppression group ( hazard ratio for recurrence , 0.66 ; 95 % CI , 0.55 to 0.80 ; P<0.001 ) . With 194 deaths ( 4.1 % of the patients ) , overall survival did not differ significantly between the two groups ( hazard ratio for death in the exemestane-ovarian suppression group , 1.14 ; 95 % CI , 0.86 to 1.51 ; P=0.37 ) . Selected adverse events of grade 3 or 4 were reported for 30.6 % of the patients in the exemestane-ovarian suppression group and 29.4 % of those in the tamoxifen-ovarian suppression group , with profiles similar to those for postmenopausal women . CONCLUSIONS In premenopausal women with hormone-receptor-positive early breast cancer , adjuvant treatment with exemestane plus ovarian suppression , as compared with tamoxifen plus ovarian suppression , significantly reduced recurrence . ( Funded by Pfizer and others ; TEXT and SOFT Clinical Trials.gov numbers , NCT00066703 and NCT00066690 , respectively . ) AIMS To evaluate a possible positive association between tamoxifen treatment and the risk of developing idiopathic venous thromboembolism ( VTE )  in women with breast cancer in the absence of clinical risk factors for venous thromboembolism other than breast cancer itself . METHODS Using information from the large UK-based General Practice Research Data base , we identified , within a cohort of more than 10000 women with breast cancer , all women who developed a first-time diagnosis of deep vein thrombosis or pulmonary embolism of uncertain cause between January 1 , 1991 and December 31 , 1996 . In a case-control analysis , we compared their tamoxifen exposure experience prior to the thromboembolic event with that of a r and omly selected group of control women with breast cancer who were matched to cases on age , year of the breast cancer diagnosis and calendar time . RESULTS We identified 25 cases of idiopathic VTE and 172 controls , all of whom had breast cancer , but were otherwise free from other risk factors for VTE . Past tamoxifen exposure was not material ly associated with an elevated risk of developing VTE , and we therefore combined never and past users as reference group . The relative risk estimate of VTE for current tamoxifen exposure , as compared with never and past use combined , was 7.1 ( 95 % CI 1.5 - 33 ) , adjusted for body mass index , smoking status and hysterectomy status . High body mass index was an independent predictor of VTE itself . CONCLUSIONS Our study provides evidence that current use of tamoxifen increases the risk of idiopathic venous thromboembolism BACKGROUND The aromatase inhibitor letrozole , as compared with tamoxifen , improves disease-free survival among postmenopausal women with receptor-positive early breast cancer . It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone . METHODS In this r and omized , phase 3 , double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women , we r and omly assigned women to receive 5 years of tamoxifen monotherapy , 5 years of letrozole monotherapy , or 2 years of treatment with one agent followed by 3 years of treatment with the other . We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol -specified up date d analysis of letrozole versus tamoxifen monother 
    Output:
    
Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non‐users and aromatase inhibitor users .
Results were also consistent with a higher risk of the vascular diseases myocardial infa rct ion and angina in aromatase inhibitor users compared with tamoxifen users , but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes .