***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: Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative , hormone-sensitive , premenopausal breast cancer . Patients were r and omised to either three cycles of cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) chemotherapy ( n=378 ) or goserelin every 28 d for 2 years ( n=393 ) . During a median follow-up of 4.9 years , 123 events were observed . The first-failure event of CMF versus goserelin , respectively , was ipsilateral locoregional recurrence ( 18 versus 20 ) , contralateral breast cancer ( 7 versus 6 ) , distant failure ( 35 versus 24 ) and death without recurrence ( 2 versus 2 ) . Forty-two ( 23 versus 19 ) deaths of any cause occurred . The estimated adjusted hazard ratio for goserelin versus CMF ( intention-to-treat analysis ) was 0.79 ( 95 % CI=0.54 - 1.14 ; P=0.19 ) . It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer The sequential doxorubicin → CMF ( CMF = cyclophosphamide , methotrexate , fluorouracil ) regimen has never been compared to CMF in a r and omised trial . The role of adding goserelin and tamoxifen after chemotherapy is unclear . In all , 466 premenopausal node-positive patients were r and omised to : ( a ) CMF × 6 cycles ( CMF ) ; ( b ) doxorubicin × 4 cycles followed by CMF × 6 cycles ( A → CMF ) ; ( c ) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( CMF → GT ) ; and ( d ) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years ( A → CMF → GT ) . The study used a 2 × 2 factorial experimental design to assess : ( 1 ) the effect of the chemotherapy regimens ( CMF vs A → CMF or arms a+c vs b+d ) and ( 2 ) the effect of adding GT after chemotherapy ( arms a+b vs c+d ) . At a median follow-up of 72 months , A → CMF as compared to CMF  significantly improved disease-free survival ( DFS ) with a multivariate hazard ratio (HR)=0.740 ( 95 % confidence interval ( CI ) : 0.556–0.986 ; P=0.040 ) and produced a nonsignificant improvement of overall survival ( OS ) ( HR=0.764 ; 95 % CI : 0.489–1.193 ) . The addition of GT after chemotherapy significantly improved DFS ( HR=0.74 ; 95 % CI : 0.555–0.987 ; P=0.040 ) , with a nonsignificant improvement of OS ( HR=0.84 ; 95 % CI : 0.54–1.32 ) . A → CMF is superior to CMF . Adding GT after chemotherapy is beneficial for premenopausal node-positive patients BACKGROUND The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes . PATIENTS AND METHODS We r and omised 333 patients to receive either LHRH agonist ( triptorelin 3.75 mg i.m . , monthly ) plus tamoxifen 30 mg/day for 3 years ( TAM-LHRHa , n=164 ) , or fluorouracil 500 mg/m2 , epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles , without any hormonal treatment ( FEC50 , n=169 ) . RESULTS The 7-year disease-free survival ( DFS ) was 76 % with TAM-LHRHa , and 72 % with FEC50 ( P=0.13 ) . The 7-year overall survival ( OS ) was 91 % and 88 % , respectively ( P=0.20 ) . The multivariate analysis confirmed that both treatments were not different for DFS and OS ( P=0.83 and P=0.41 , respectively ) . Amenorrhoea occurred in 64 % of patients treated with FEC50 ; it was temporary in 58 % of cases after hormonotherapy and in 31 % after chemotherapy . CONCLUSION In intermediate-risk breast cancer , complete hormonal blockade and chemotherapy provided similar outcomes .  Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients , considering the preference of patients in terms of quality of life GABG-IV B-93 is a prospect i ve , r and omised study comparing goserelin  ( n=384 ) with no further treatment  ( n=392 ) in hormone receptor (HR)-negative breast cancer patients ( n=465 ) after 3 cycles cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) for patients with 0 - 3 positive lymph nodes ( LN ) or 4 cycles epirubicin , cyclophosphamide ( EC ) followed by 3 cycles CMF for patients with 4 - 9 positive LN . After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1 - 9+LN ( n=311 ) . After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin . The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 ( goserelin versus control , 95 % confidence interval [ CI ] 0.72 - 1.42 , P=0.97 ) and 0.77 in HR-positive patients ( 95 % CI 0.47 - 1.24 , P=0.27 ) . These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients A total of 16 premenopausal women with metastatic breast cancer ( N=13 ) or locally advanced primary breast cancer ( N=3 ) were treated with a combination of a gonadotropin-releasing hormone agonist goserelin , and a selective aromatase inhibitor anastrozole .  All had previously been treated with goserelin and tamoxifen .  In all , 12 patients ( 75 % ) achieved objective response or durable stable disease at 6 months , with a median duration of remission of 17 + months ( range 6–47 months ) . Four patients still have clinical benefit . Introduction of goserelin and tamoxifen result ed in an 89 % reduction in mean oestradiol levels ( pretreatment vs 6 months=224 vs 24 pmol l−1 ) ( P<0.0001 ) . Substitution of tamoxifen by anastrozole on progression result ed in a further 76 % fall ( to 6 pmol l−1 at 3 months ) ( P<0.0001 ) . Treatment with goserelin and tamoxifen led to a 90 % fall in the mean follicle-stimulating hormone ( P<0.001 ) . This was reversed once therapy was changed to goserelin and anastrozole . A similar initial reduction was seen in the mean luteinising hormone levels , but substitution of tamoxifen by anastrozole on progression result ed in no significant change . Goserelin and tamoxifen did not lead to any significant change in testosterone and and rostenedione levels . The combined use of goserelin and anastrozole as second-line endocrine therapy produces a significant clinical response of worthwhile duration , with demonstrable endocrine changes , in premenopausal women with advanced breast cancer , and offers them another therapeutic option . Further studies involving more patients and longer follow-up are indicated PURPOSE Ovarian suppression with luteinizing hormone-releasing hormone ( LHRH ) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor ( ER ) -positive breast cancer . Whereas monthly LHRH agonist therapy has been well established , the value of every-3-months ( 3-monthly ) formulations is unclear . PATIENTS AND METHODS This r and omized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate ( LAD-3 M ; n = 299 ) and chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ; n = 300 ) in pre- or perimenopausal patients with ER-positive , node-positive breast cancer . RESULTS With a median follow-up of 5.8 years , recurrence-free survival was similar for patients treated with LAD-3 M or CMF ( hazard ratio [ HR ] , 1.19 ; 95 % CI , 0.94 to 1.51 ; P = .15 ) . There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age , progesterone receptor ( PR ) status , nodal status , hormone levels , or menstrual recovery after treatment . Exploratory overall survival analysis favored LAD-3 M ( HR , 1.50 ; 95 % CI , 1.13 to 1.99 ; P = .005 ) . Chemotherapy-related adverse effects such as nausea , vomiting , and alopecia were more common with CMF , whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3 M . CONCLUSION The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor-positive , node-positive breast cancer that is not inferior to CMF PURPOSE To compare quality of life ( QoL ) in premenopausal and perimenopausal patients with node-positive , early breast cancer treated with the endocrine agent goserelin ( Zoladex ; AstraZeneca Pharmaceuticals LP , Wilmington , DE ) or cyclophosphamide + methotrexate + fluorouracil ( CMF ) . PATIENTS AND METHODS Patients from 86 centers worldwide were r and omly assigned to receive either goserelin ( 3.6 mg every 28 days for 2 years ; n = 514 ) or CMF ( six 28-day cycles ; n = 496 ) , and were included in the QoL study . QoL was assessed using a self-administered patient question naire that consisted of 39 items from the Rotterdam Symptom Checklist , including dimensions evaluating physical and psychological symptom distress , activities of daily living , hormonal effects , and an assessment of overall QoL. RESULTS Early benefits were noted during months 3 to 6 of treatment , for goserelin compared with CMF . Significant differences were found for changes in overall QoL ( eg , 6.96 + /- 0.88 v 0.69 + /- 0.92 at 6 months ; P < .0001 ) and for physical symptom distress , activity levels , and " effort to cope with illness " dimensions . At 1 , 2 , and 3 years , there were no significant differences in overall QoL or specific QoL dimensions . Scores for hormonal symptoms were worse with goserelin during the 2-year goserelin treatment period ; however , this trend was reversed at 3 years . CONCLUSION Goserelin offers improved overall QoL during the first 6 months of therapy compared with CMF chemotherapy in premenopausal and perimenopausal patients with early breast cancer . Coupled with equivalent efficacy in estrogen receptor-positive patients , these data support the use of goserelin as an alternative to CMF in premenopausal and perimenopausal patients with estrogen receptor-positive , node-positive early breast cancer OBJECTIVE Goserelin ( GOS ) therapy in an adjuvant setting for estrogen receptor(ER)-positive premenopausal patients with breast cancer was assessed in a r and omised comparative study . METHODS ER positive premenopausal patients with n + or n 0 and T > or = 3 cm received tamoxifen ( TAM ) 20 mg/day , GOS 3.6 mg/4 weeks or GOS + TAM for 2 years , and the clinical efficacy and safety of these regimens were assessed . RESULTS In the data analysis of total 207 patients , hazard ratios of disease free survival ( DFS ) and overall survival ( OS ) in the GOS group compared to the TAM group were 0.87 and 2.10,respectively . The incidence of adverse drug reactions was similar ( 42 - 55 % ) in all three groups . Since the number of patients in this study did not reach the target number , the efficacy could not be assessed from a statistical aspect . Therefore , meta- analysis with similar foreign studies ( ZIPP ) was implemented . The results of meta- analysis showed that the hazard ratios of DFS and OS in the GOS group compared to the non-GOS group were 0.83 and 0.85 , respectively . CONCLUSION Although the analysis of 207 patients did not show any statistically significant difference between 
    Output:
    
For most of the treatment comparisons there are too few trials , too few r and omised patients , or too little follow up to draw reliable estimates of the relative effects of different treatments.(A ) LHRH monotherapy : results suggest that adjuvant LHRH agonist monotherapy is similar to older chemotherapy protocol s ( eg .
CMF ) in terms of recurrence-free and overall survival in ER+ patients .
Endocrine therapy with LHRH agonists appears to have fewer side-effects than the forms of chemotherapy assessed .
The optimal duration of LHRH therapy in the adjuvant setting is unclear .
Overall , the data from currently published clinical trials of LHRH agonists in the adjuvant setting for premenopausal women with endocrine-sensitive breast cancer are supportive of clinical benefit .