***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: BACKGROUND Clinical trials have shown that trastuzumab , a recombinant monoclonal antibody against HER2 receptor , significantly improves overall survival and disease-free survival in women with HER2-positive early breast cancer , but long-term follow-up data are needed . We report the results of comparing observation with two duration s of trastuzumab treatment at a median follow-up of 11 years , for patients enrolled in the HERA ( HERceptin Adjuvant ) trial . METHODS HERA ( BIG 1 - 01 ) is an international , multicentre , open-label , phase 3 r and omised trial of 5102 women with HER2-positive early breast cancer , who were enrolled from hospitals in 39 countries between Dec 7 , 2001 , and June 20 , 2005 . After completion of all primary therapy ( including , surgery , chemotherapy , and radiotherapy as indicated ) , patients were r and omly assigned ( 1:1:1 ) to receive trastuzumab for 1 year ( once at 8 mg/kg of bodyweight intravenously , then 6 mg/kg once every 3 weeks ) or for 2 years ( with the same dose schedule ) , or to the observation group . Primary endpoint is disease-free survival , and analyses are in the intention-to-treat population . Hazard ratios ( HRs ) were estimated from Cox models , and survival curves were estimated by the Kaplan-Meier method . Comparison of 2 years versus 1 year of trastuzumab is based on 366-day l and mark analyses . This study is registered with Clinical Trials.gov ( NCT00045032 ) . FINDINGS Of the 5102 women r and omly assigned in the HERA trial , three patients had no evidence of having provided written informed consent to participate . We followed up the intention-to-treat population of 5099 patients ( 1697 in observation , 1702 in 1-year trastuzumab , and 1700 in 2-years trastuzumab groups ) . After a median follow-up of 11 years ( IQR 10·09 - 11·53 ) , r and om assignment to 1 year of trastuzumab significantly reduced the risk of a disease-free survival event ( HR 0·76 , 95 % CI 0·68 - 0·86 ) and death ( 0·74 , 0·64 - 0·86 ) compared with observation . 2 years of adjuvant trastuzumab did not improve disease free-survival outcomes compared with 1 year of this drug ( HR 1·02 , 95 % CI 0·89 - 1·17 ) . Estimates of 10-year disease-free survival were 63 % for observation , 69 % for 1 year of trastuzumab , and 69 % for 2 years of trastuzumab . 884 ( 52 % ) patients assigned to the observation group selectively crossed over to receive trastuzumab . Cardiac toxicity remained low in all groups and occurred mostly during the treatment phase . The incidence of secondary cardiac endpoints was 122 ( 7·3 % ) in the 2-years trastuzumab group , 74 ( 4·4 % ) in the 1-year trastuzumab group , and 15 ( 0·9 % ) in the observation group . INTERPRETATION 1 year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improves long-term disease-free survival , compared with observation . 2 years of trastuzumab had no additional benefit . FUNDING F Hoffmann-La Roche ( Roche ) BACKGROUND We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer . METHODS The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks ( group 1 ) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel ( group 2 ) . The North Central Cancer Treatment Group trial N9831 compared three regimens : doxorubicin and cyclophosphamide followed by weekly paclitaxel ( group A ) , the same regimen followed by 52 weeks of trastuzumab after paclitaxel ( group B ) , and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel ( group C ) . The studies were amended to include a joint analysis comparing groups 1 and A ( the control group ) with groups 2 and C ( the trastuzumab group ) . Group B was excluded because trastuzumab was not given concurrently with paclitaxel . RESULTS By March 15 , 2005 , 394 events ( recurrent , second primary cancer , or death before recurrence ) had been reported , triggering the first scheduled interim analysis . Of these , 133 were in the trastuzumab group and 261 in the control group ( hazard ratio , 0.48 ; P<0.0001 ) . This result crossed the early stopping boundary . The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years . Trastuzumab therapy was associated with a 33 percent reduction in the risk of death ( P=0.015 ) . The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831 . CONCLUSIONS Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer . ( Clinical Trials.gov numbers , NCT00004067 and NCT00005970 . Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Background . Little information is available about survival outcomes of patients with HER2-positive early breast cancer treated with adjuvant capecitabine-containing chemotherapy with or without trastuzumab . Patients and methods . One thous and and five hundred patients with early breast cancer were entered to the Finl and Capecitabine trial ( FinXX ) between January 2004 and May 2007 , and were r and omly assigned to receive either three cycles of adjuvant TX ( docetaxel , capecitabine ) followed by three cycles of CEX ( cyclophosphamide , epirubicin , capecitabine ; TX-CEX ) or three cycles of docetaxel followed by three cycles of CEF ( cyclophosphamide , epirubicin , fluorouracil ; T-CEF ) . The primary endpoint was recurrence-free survival ( RFS ) . The study protocol was amended in May 2005 while study accrual was ongoing to allow adjuvant trastuzumab for patients with HER2-positive cancer . Of the 284 patients with HER2-positive cancer accrued to FinXX , 176 ( 62.0 % ) received trastuzumab after amending the study protocol , 131 for 12 months and 45 for nine weeks . The median follow-up time was 6.7 years . Results . Patients with HER2-positive cancer who received trastuzumab had better RFS than those who did not ( five-year RFS 89.2 % vs. 75.9 % ; HR 0.41 , 95 % CI 0.23–0.72 ; p = 0.001 ) . Patients treated with trastuzumab for 12 months or nine weeks had similar RFS . There was no significant interaction between trastuzumab administration and the type of chemotherapy . Four ( 2.3 % ) patients treated with trastuzumab had heart failure or left ventricular dysfunction , three of these received capecitabine . Conclusion . Adjuvant trastuzumab improves RFS of patients treated with TX-CEX or T-CEF . Few patients had cardiac failure PURPOSE To evaluate the efficacy of trastuzumab in patients with node-positive breast cancer treated with surgery , adjuvant chemotherapy , radiotherapy , and hormone therapy if applicable . PATIENTS AND METHODS Three thous and ten patients with operable node-positive breast cancer were r and omly assigned to receive adjuvant anthracycline-based chemotherapy with or without docetaxel .  Patients who presented human epidermal growth factor receptor 2 ( HER2 ) -overexpressing tumors were secondary r and omly assigned to either a sequential regimen of trastuzumab ( 6 mg/kg every 3 weeks ) for 1 year or observation . The primary end point was disease-free survival ( DFS ) . RESULTS Overall 528 patients were r and omly assigned between trastuzumab ( n = 260 ) and observation ( n = 268 ) arm . Of the 234 patients ( 90 % ) who received at least one administration of trastuzumab , 196 ( 84 % ) received at least 6 months of treatment , and 41 ( 18 % ) discontinued treatment due to cardiac events ( any grade ) . At the date of analysis ( October 2007 ) , 129 DFS events were recorded . R and om assignment to the trastuzumab arm was associated with a nonsignificant 14 % reduction in the risk of relapse ( hazard ratio , 0.86 ; 95 % CI , 0.61 to 1.22 ; P = .41 , log-rank stratified on pathologic node involvement ) . Three-year DFS rates were 78 % ( 95 % CI , 72.3 to 82.5 ) and 81 % ( 95 % CI , 75.3 to 85.4 ) in the observation and trastuzumab arms , respectively . CONCLUSION After a 47-month median follow-up , 1 year of trastuzumab given sequentially after adjuvant chemotherapy was not associated with a statistically significant decrease in the risk of relapse BACKGROUND Trastuzumab -- a humanised monoclonal antibody against HER2 - -has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer . We investigated the drug 's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant ( HERA ) study . METHODS HERA is an international multicentre r and omised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after st and ard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer . 5102 women participated in the trial ; we analysed data from 1703 women who had been r and omised for treatment with trastuzumab for 1 year and 1698 women from the control group , with median follow-up of 23.5 months ( range 0 - 48 months ) . The primary endpoint of the trial was disease-free survival . Here , we assess overall survival , a secondary endpoint . Analyses were done on an intent-to-treat basis . This trial is registered with the European Clinical Trials Data base , number 2005 - 002385 - 11 . FINDINGS 97 ( 5.7 % ) patients r and omised to observation alone and 58 ( 3.4 % ) patients r and omised to 1 year of treatment with trastuzumab were lost to follow-up . 172 women stopped trastuzumab prematurely . 59 deaths were reported for trastuzumab and 90 in the control group . The unadjusted hazard ratio ( HR ) for the risk of death with trastuzumab compared with observation alone was 0.66 ( 95 % CI 0.47 - 0.91 ; p=0.0115 ) . 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group . The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 ( 0.54 - 0.76 ; p<0.0001 ) . INTERPRETATION Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years . The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer PURPOSE Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer .  Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 ( HER2 ) -positive cancer are unknown . PATIENTS AND METHODS One thous and ten women with axillary node-positive or high-risk node-negative breast cancer were r and omly assigned to receive three cycles of docetaxel or vinorelbine , followed in both groups by three cycles of fluorouracil , epirubicin , and cyclophosphamide ( FEC ) .  Women with HER2-positive cancer ( n = 232 ) were further assigned to either receive or not receive trastuz 
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Results : Based on the eight included studies in the review , combining trastuzumab with chemotherapy continues to show lowered death and relapse risks by one-third .
The decision to initiate trastuzumab , however , needs to be prudently deliberated as two to three times more cardiotoxicity risk was shown to be associated with its use .
Conclusion : Administering adjuvant trastuzumab in a weekly cycle concurrently with anthracycline-taxane chemotherapy regimen appears to be a preferable option to optimize its favorable effect in improving DFS and to prevent significantly higher risk for cardiotoxic effects