***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 MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival ( DFS ) for letrozole [ hazard ratio ( HR ) 0.57 , P = 0.00008 ] . The trial was unblinded and placebo patients were offered letrozole . PATIENTS AND METHODS An intent-to-treat analysis of all outcomes , before and after unblinding , on the basis of the original r and omization was carried out . RESULTS In all , 5187 patients were r and omly allocated to the study at baseline and , at unblinding , 1579 ( 66 % ) of 2383 placebo patients accepted letrozole . At median follow-up of 64 months ( range 16 - 95 ) , 399 recurrences or contralateral breast cancers ( CLBCs ) ( 164 letrozole and 235 placebo ) occurred . Four-year DFS was 94.3 % ( letrozole ) and 91.4 % ( placebo ) [ HR 0.68 , 95 % confidence interval ( CI ) 0.55 - 0.83 , P = 0.0001 ] and showed superiority for letrozole in both node-positive and -negative patients . Corresponding 4-year distant DFS was 96.3 % and 94.9 % ( HR 0.80 , 95 % CI 0.62 - 1.03 , P = 0.082 ) . Four-year overall survival was 95.1 % for both groups . The annual rate of CLBC was 0.28 % for letrozole and 0.46 % for placebo patients ( HR 0.61 , 95 % CI 0.39 - 0.97 , P = 0.033 ) . CONCLUSIONS Patients originally r and omly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC , despite 66 % of placebo patients taking letrozole after unblinding 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 Summary Introduction . Long-term endocrine therapy for breast cancer may have clinical implication s as drugs that potentially alter the lipid profile may increase the risk of developing cardiovascular disease . In this study , a companion sub- protocol to the TEAM ( Tamoxifen and Exemestane Adjuvant Multicenter ) International trial , we compared the effect of the steroidal aromatase inactivator exemestane on the lipid profile of postmenopausal women with early breast cancer in the adjuvant setting to that of tamoxifen . Patients and methods . In this open-label , r and omized , parallel group study , 176 postmenopausal patients with estrogen and /or progesterone receptor positive early breast cancer were r and omized to either  adjuvant exemestane ( 25 mg/day ; n = 90 ) or tamoxifen ( 20 mg/day ; n = 86 ) . Assessment s of total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) and serum triglycerides ( TRG ) were performed at baseline and every 3 months for the first 12 months . Results . Serum triglyceride levels were consistently increased above baseline throughout the study in the tamoxifen arm , while there was a trend towards reduction in the exemestane arm . There was also an overall trend for tamoxifen to decrease the levels of LDL throughout the study period . Exemestane did not demonstrate any other significant change in HDL levels ; however , there was a consistent trend for a reduction in total cholesterol in both treatment arms . The atherogenic risk determined by the TC : HDL ratio remained stable in both arms throughout the treatment period . Conclusions . Exemestane appears to have a neutral effect on total cholesterol and HDL levels . Unlike tamoxifen ’s positive effect on LDL levels , exemestane does not significantly alter LDL levels . Tamoxifen on the other h and increases triglyceride levels , while exemestane results in a beneficial reduction in TRG levels . These data offer additional information with regard to the safety and tolerability of exemestane in postmenopausal breast cancer patients and support further investigation of its potential usefulness in the adjuvant setting 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 The purpose of this study was to evaluate changes in serum lipid parameters { cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides and lipoprotein(a ) [ Lp(a ) ] } , in postmenopausal women receiving letrozole or placebo after adjuvant tamoxifen for early stage breast cancer ( NCIC CTG MA.17L ) . PATIENTS AND METHODS MA.17L is a sub study of MA.17 , a r and omized , double-blind , placebo-controlled trial of letrozole 2.5 mg taken daily for 5 years in postmenopausal women with primary breast cancer completing approximately 5 years of prior adjuvant tamoxifen .  Patients consenting to participate in this companion study had blood drawn and lipid parameters ( total cholesterol , HDL cholesterol , LDL cholesterol , Lp(a ) , triglycerides ) evaluated at baseline , 6 months , 12 months and yearly thereafter until completion of protocol therapy . It was required that women be non-hyperlipidemic and not taking lipid-lowering drugs at time of entry on this trial . RESULTS Three hundred and forty seven women were enrolled in the study . The letrozole and the placebo groups demonstrated marginally significant differences in the percentage change from baseline in HDL cholesterol at 6 months ( P=0.049 ) , in LDL cholesterol at 12 months ( P=0.033 ) and triglycerides at 24 months ( P=0.036 ) . All comparisons of lipid parameters at other time points were not significantly different between the two treatment groups . No statistically significant differences in the number of patients exceeding the thresholds defined for the lipid parameters were found between the two treatment groups . CONCLUSIONS The MA.17 trial demonstrated a significant improvement in disease-free survival with the use of letrozole as extended adjuvant therapy post tamoxifen . Results from this study suggests that letrozole does not significantly alter serum cholesterol , HDL cholesterol , LDL cholesterol , triglycerides or Lp(a ) in non-hyperlidiemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy . These findings further support the tolerability of extended adjuvant letrozole in postmenopausal women following st and ard tamoxifen therapy Tamoxifen remains one of the most effective agents in the treatment of breast cancer . However , the development of persistent side effects from chronic administration of tamoxifen remains a concern . The objective of this project was to investigate the effect of long-term tamoxifen therapy ( 2 years ) on the plasma lipoprotein concentration and lipid transfer activity in postmenopausal women diagnosed with breast cancer . Two distinct population s of breast cancer patients were recruited for this study : postmenopausal women diagnosed with breast cancer that have never been on tamoxifen and postmenopausal women diagnosed with breast cancer that have been on tamoxifen ( 20 mg once daily ) for 2 years ( n = 18 each group ) . Blood was collected for total and lipoprotein cholesterol ( C ) and triglyceride ( TG ) analysis by established enzymatic assays prior to and 2 years following the initial tamoxifen dose . To determine the effect of tamoxifen administration on lipid transfer between lipoprotein fractions , lipid transfer protein ( LTP I ) activity was measured . A significant decrease in total and low-density lipoprotein ( LDL ) cholesterol levels and a moderate increase in high-density lipoprotein ( HDL ) triglyceride levels were observed in plasma sample s from postmenopausal women with breast cancer who were administered tamoxifen for 2 years . No significant differences in total and lipoprotein C and TG plasma levels were observed in sample s from women with breast cancer that never received tamoxifen .  LTP I activity was significantly decreased in patients receiving tamoxifen compared to patients who never received tamoxifen . These specific tamoxifen-induced effects may be important for a number of reasons . Although the apparent decrease in total C and LDL-C levels are favorable for reducing the risk of cardiovascular disease , the elevated levels of HDL-TG have been related to the increased risk of ischemic heart disease . Furthermore , underst and ing how tamoxifen influences LTP I activity provides valuable insight into how the administration of tamoxifen modifies plasma lipoprotein-lipid levels Recent studies have shown that administering the aromatase inhibitor exemestane after 2–3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with st and ard 5-year tamoxifen treatment . Although many of the adverse effects associated with exemestane and tamoxifen have been analysed , there are no comparative data concerning body weight and body composition . The aim of this r and omised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane .  In total , 60 overweight or obese postmenopausal patients were enrolled . Their anthropometric data , body composition , including fat mass ( FM ) and fat-free mass ( FFM ) , and lipid profiles , caloric intake and physical activity were assessed 1 week before r and omisation , and 6 and 12 months later . In all , 55 patients ( 27 on tamoxifen and 28 on exemestane )  completed the 1-year study period . Fat mass had significantly decreased by month 12 in the exemestane , but not in the tamoxifen group ; the between- 
    Output:
    
Overall , available data did not show any definitive patterns or suggest an unfavourable effect of AIs on plasma lipoproteins from baseline to follow-up assessment in patients with hormone receptor-positive early breast cancer .
Changes that occurred in plasma lipoproteins were observed soon after initiation of AI therapy and generally remained stable throughout the studies .