***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 The study compares letrozole and aminoglutethimide ( AG ) , a st and ard therapy for postmenopausal women with advanced breast cancer , previously treated with antioestrogens . PATIENTS AND METHODS 555 women were r and omly assigned letrozole 2.5 mg once daily ( n = 185 ) , letrozole 0.5 mg once daily ( n = 192 ) or aminoglutethimide 250 mg twice daily with corticosteroid support ( n = 178 ) in an open-label , multicentre trial . The primary endpoint was objective response rate ( ORR ) , with time events as secondary . ORR was analysed nine months after enrollment of the last patient , while survival was analysed 15 months after the last patient was enrolled . We report the results of these analyses plus an extended period of observation ( covering a total duration of approximately 45 months ) to determine the duration of response and clinical benefit . RESULTS Overall objective response rates ( complete + partial ) of 19.5 % , 16.7 % and 12.4 % were seen for letrozole 2.5 mg , 0.5 mg and AG respectively . Median duration of response and stable disease was longest for letrozole 2.5 mg ( 21 months ) compared with letrozole 0.5 mg ( 18 months ) and AG ( 14 months ) . Letrozole 2.5 mg was superior to AG in time to progression , time to treatment failure and overall survival . Treatment-related adverse events occurred in fewer patients on letrozole ( 33 % ) than on AG ( 46 % ) . Transient nausea was the most frequent event with letrozole ( 7 % on 0.5 mg , 10 % on 2.5 mg , 10 % on AG ) , rash with AG ( 11 % , 1 % on 0.5 mg , 3 % on 2.5 mg letrozole ) . CONCLUSIONS Letrozole 2.5 mg offers longer disease control than aminoglutethimide and letrozole 0.5 mg in the treatment of postmenopausal women with advanced breast cancer , previously treated with anti-oestrogens Background : We investigated whether body mass index ( BMI ) can be used as a predictive parameter indicating patients who benefit from  extended aromatase inhibitor ( AI ) treatment .  Methods : The ABCSG-6a trial re-r and omised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil . In this retrospective analysis , we investigated the prognostic and predictive impact of BMI on disease outcome and safety . Results : In all , 634 patients ( 177 normal weight , 307 overweight , and 150 obese ) patients were included in this analysis . Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence ( disease-free survival ( DFS ) HR 0.48 ; P=0.02 ) and death ( HR 0.45 ; P=0.06 ) and had only a fifth of the risk of distant metastases ( HR 0.22 ; P=0.05 ) compared with normal weight patients without any further treatment . In contrast , overweight+obese patients derived no benefit from additional 3 years of anastrozole ( DFS HR 0.93 ; P=0.68 ; distant recurrence-free survival HR 0.91 ; P=0.78 ; and OS HR 0.9 ; P=0.68 ) . The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment ( P=0.07 ) . Conclusion : Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer 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 Obesity , defined as a body mass index ( BMI ) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates . The present subgroup analysis of the German BRENDA-cohort aim ed to investigate the correlation between BMI , recurrence-free survival ( RFS ) and adjuvant endocrine therapy .  In this subgroup analysis , 4,636 patients were retrospectively examined using multivariate analyses . Overall 3,759 ( 81.1 % ) patients had a BMI < 30 ( non-obese ) and 877 ( 18.9 % ) a BMI ≥30 ( obese ) . In the group of all 3,896 ( 84.0 % ) patients with hormone-receptor-positive ( HR+ ) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese ( P = 0.002 ; HR = 1.45 ( 95 % CI : 1.15–1.83 ) ) , also after adjustment for Nottingham Prognostic Index ( NPI ) ( P = 0.028 ; HR = 1.30 ( 95 % CI : 1.03–1.65 ) ) . In hormone-receptor-negative ( HR− ) patients  BMI had no influence on RFS ( P = 0.380 ; HR = 1.20 ( 95 % CI : 0.80–1.81 ) ) . Considering menopausal status , a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients ( P < 0.001 ; HR = 1.61 ( 95 % CI : 1.24–2.09 ) ) , whereas the premenopausal patient group only showed a trend towards a shorter RFS ( P = 0.202 ; HR = 1.44 ( 95 % CI : 0.82–2.53 ) ) . The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit  for aromatase inhibitors ( AI ) compared to tamoxifen ( RFS : P = 0.486 ; HR = 1.29 ( 95 % CI : 0.63–2.62 ) , while obese patients tended to benefit more from tamoxifen ( RFS : P = 0.289 ; HR = 0.65 ( 95 % CI : 0.29–1.45 ) ) . In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer . Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen . Prospect i ve studies to optimise the therapy of obese breast cancer patients are urgently needed PURPOSE To compare the effects of the two novel , potent , nonsteroidal aromatase inhibitors anastrozole and letrozole on total-body aromatization and plasma estrogen levels . PATIENTS AND METHODS Twelve postmenopausal women with estrogen receptor-positive , metastatic breast cancer were treated with anastrozole 1 mg orally ( PO ) and letrozole 2.5 mg PO once daily , each given for a time interval of 6 weeks in a r and omized sequence . Total-body aromatization was determined before treatment and at the end of each treatment period using a dual-label isotopic technique involving isolation of the metabolites with high-performance liquid chromatography . Plasma levels of estrone ( E(1 ) ) , estradiol ( E(2 ) ) , and estrone sulfate ( E(1)S ) were determined in sample s obtained before each injection using highly sensitive radioimmunoassays . RESULTS Pretreatment aromatase levels ranged from 1.68 % to 4.27 % . On-treatment levels of aromatase were detectable in 11 of 12 patients during treatment with anastrozole ( mean percentage inhibition in the whole group , 97.3 % ) but in none of the 12 patients during treatment with letrozole ( > 99.1 % suppression in all patients ; Wilcoxon , P = .0022 , comparing the two drug regimens ) . Treatment with anastrozole  suppressed plasma levels of E(1 ) , E(2 ) , and E(1)S by a mean of 81.0 % , 84.9 % , and 93.5 % , respectively , whereas treatment with letrozole caused a corresponding decrease of 84.3 % , 87.8 % and 98.0 % , respectively . The suppression of E(1 ) and E(1)S was found to be significantly better during treatment with letrozole compared with anastrozole ( P = .019 and .0037 , respectively ) . CONCLUSION This study revealed letrozole ( 2.5 mg once daily ) to be a more potent suppressor of total-body aromatization and plasma estrogen levels compared with anastrozole ( 1 mg once daily ) in postmenopausal women with metastatic breast cancer The aim of this study was to compare the efficacy and tolerability of the new aromatase inhibitor ' ARIMIDEX ' ( anastrozole ) with megestrol acetate in the treatment of advanced breast cancer in postmenopausal women .  Anastrozole is a new potent and highly selective non-steroidal aromatase inhibitor . We conducted a prospect i ve r and omised trial comparing two doses of anastrozole ( 1 and 10 mg orally once daily ) with megestrol acetate ( 40 mg orally four times daily ) in postmenopausal patients with advanced breast cancer who progressed after prior tamoxifen therapy . All patients were analysed for efficacy as r and omised ( intention to treat ) and for tolerability as per treatment received . Of the 378 patients who entered the study , 135 were r and omised to anastrozole 1 mg , 118 to anastrozole 10 mg , and 125 patients to megestrol acetate .  After a median follow-up of 192 days , response rate which included complete response , partial response and patients who had disease stabilisation for 6 months or more was 34 % for anastrozole 1 mg , 33.9 % for anastrozole 10 mg and 32.8 % for megestrol acetate . There were no statistically significant differences between either dose of anastrozole and megestrol acetate in terms of objective response rate , time to objective progression of disease or time to treatment failure . The three treatments were generally well tolerated , but more patients on megestrol acetate reported weight gain , oedema and dyspnoea as adverse events while more patients on anastrozole reported gastro-intestinal disorders , usually in the form of mild transient nausea . Patients on anastrozole did not report higher incidences of oestrogen withdrawal symptoms .  Anastrozole is an effective and well tolerated treatment for postmenopausal patients with advanced breast cancer . The higher 10 mg dose did not result in additional clinical benefit , but was well tolerated reflecting the good therapeutic margin with anastrozole . Based on this data , anastrozole 1 mg should be the recommended therapeutic dose BACKGROUND Anastrozole is a new oral aromatase inhibitor with highly potent and selective activity for the aromatase enzyme . In a Phase III trial , the efficacy and tolerability of anastrozole , given in doses of 1 and 10 mg orally once daily , and megestrol acetate , given in doses of 40 mg orally 4 times daily , were compared in 386 postmenopausal women with advanced breast carcinoma who progressed after tamoxifen therapy . METHODS The trial was r and omized , double blind for anast 
    Output:
    
However , the systematic review showed a trend towards a negative effect of obesity on  AI efficacy .
There is evidence of a negative effect of obesity on  AI efficacy in postmenopausal hormone receptor-positive breast cancer , but the size of the effect can not be assessed .