***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 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 report cardiac events in the Persephone trial which compares 6–12 months of adjuvant trastuzumab in women with confirmed HER2-positive , early-stage breast cancer . Methods : Clinical cardiac events were defined as any of the following : symptoms and /or signs of congestive heart failure ( CHF ) and new or altered CHF medication . In addition , left ventricular ejection fraction ( LVEF ) was measured at baseline and then 3 monthly for 12 months . Results : A total of 2500 patients , aged 22–82 , were included : 1251 r and omised to 12 months and 1249 to 6 months of trastuzumab treatment . A total of 93 % ( 2335/2500 ) received anthracyclines , 49 % of these ( 1136/2335 ) with taxanes .  Cardiotoxicity delayed treatment in 6 % of 12-month and 4 % of 6-month patients ( P=0.01 ) , and stopped treatment early in 8 % ( 96/1214 ) of 12-month and 4 % ( 45/1216 ) of 6-month patients ( P<0.0001 ) . Between 7 and 12 months , more 12-month than 6-month patients had LVEFs<50 % ( 8 % vs 5 % ; P=0.004 ) . LVEFs showed quadratic change over time , and 6-month patients had a more rapid recovery ( P=0.02 ) . In a l and mark analysis twice as many 12-month patients , free of cardiac events at 6 months , had cardiac problems in months 7–12 ( 6 % ( 66/1046 ) vs 3 % ( 29/1035 ) of 6-month patients ( P=0.0002 ) ) . Lower baseline LVEF predicted more cardiac dysfunction in both arms ( reference ⩾65 % : 55 to < 65 % OR 1.61 ( 95 % CI 1.26–2.04 ) ; < 55 % OR 5.22 ( 3.42–7.95 ) ) as did increasing age ( reference < 50 : 50–59 OR 1.58 ( 1.17–2.12 ) , 60–69 OR 1.91 ( 1.42–2.57 ) ) 70 + OR 2.72 ( 1.82–4.08 ) ) and prior use of cardiac medication ( OR 8.46 ( 4.69–15.25 ) ) . > 3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients ( OR 1.41 ( 1.04–1.90 ) ) , and not for 6-month patients ( OR 1.28 ( 0.91–1.79 ) ) . Conclusions : We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months . This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment . If 6 months is proven to have non-inferior outcomes to 12 months treatment , these data would support 6 months as the st and ard of care BACKGROUND In the primary analysis of the NeoSphere trial , patients given neoadjuvant pertuzumab , trastuzumab , and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery . Here , we report 5-year progression-free survival , disease-free survival , and safety . METHODS In this multicentre , open-label , phase 2 r and omised trial in hospitals and medical clinics , treatment-naive adults with locally advanced , inflammatory , or early-stage HER2-positive breast cancer were r and omly assigned ( 1:1:1:1 ) to receive four neoadjuvant cycles of trastuzumab ( 8 mg/kg loading dose , followed by 6 mg/kg every 3 weeks ) plus docetaxel ( 75 mg/m(2 ) every 3 weeks , increasing to 100 mg/m(2 ) from cycle 2 if tolerated ; group A ) , pertuzumab ( 840 mg loading dose , followed by 420 mg every 3 weeks ) and trastuzumab plus docetaxel ( group B ) , pertuzumab and trastuzumab ( group C ) , or pertuzumab and docetaxel ( group D ) . After surgery , patients received three cycles of FEC ( fluorouracil 600 mg/m(2 ) , epirubicin 90 mg/m(2 ) , and cyclophosphamide 600 mg/m(2 ) ) every 3 weeks ( patients in group C received four cycles of docetaxel prior to FEC ) , and trastuzumab 6 mg/kg every 3 weeks to complete 1 year 's treatment ( 17 cycles in total ) . R and omisation was done by a central centre using dynamic allocation , stratified by operable , locally advanced , and inflammatory breast cancer , and by oestrogen and /or progesterone receptor positivity . Safety analyses were done according to treatment received . The primary endpoint ( pathological complete response ) was previously reported ; secondary endpoints reported here are 5-year progression-free survival ( analysed in the intention-to-treat population ) and disease-free survival ( analysed in patients who had surgery ) . Secondary and exploratory analyses were not powered for formal statistical hypothesis testing , and therefore results are for descriptive purpose s only . The study ended on Sept 22 , 2014 ( last patient , last visit ) . This study is registered with Clinical Trials.gov , number NCT00545688 . FINDINGS Between Dec 17 , 2007 , and Dec 22 , 2009 , 417 eligible patients were r and omly assigned to group A ( 107 patients ) , group B ( 107 patients ) , group C ( 107 patients ) , or group D ( 96 patients ) . One patient in group A withdrew before treatment . One patient assigned to group D received group A treatment , one patient assigned to group D received group B treatment , and one patient assigned to group B received group C treatment . At clinical cutoff , 87 patients had progressed or died . 5-year progression-free survival rates were 81 % ( 95 % CI 71 - 87 ) for group A , 86 % ( 77 - 91 ) for group B , 73 % ( 64 - 81 ) for group C , and 73 % ( 63 - 81 ) for group D ( hazard ratios 0·69 [ 95 % CI 0·34 - 1·40 ] group B vs group A , 1·25 [ 0·68 - 2·30 ] group C vs group A , and 2·05 [ 1·07 - 3·93 ] group D vs group B ) . Disease-free survival results were consistent with progression-free survival results and were 81 % ( 95 % CI 72 - 88 ) for group A , 84 % ( 72 - 91 ) for group B , 80 % ( 70 - 86 ) for group C , and 75 % ( 64 - 83 ) for group D. Patients who achieved total pathological complete response ( all groups combined ) had longer progression-free survival compared with patients who did not ( 85 % [ 76 - 91 ] in patients who achieved total pathological response vs 76 % [ 71 - 81 ] in patients who did not achieve total pathological response ; hazard ratio 0·54 [ 95 % CI 0·29 - 1·00 ] ) . There were no new or long-term safety concerns and tolerability was similar across groups ( neoadjuvant and adjuvant treatment periods combined ) . The most common grade 3 or worse adverse events were neutropenia ( group A : 71 [ 66 % ] of 107 patients ; group B : 59 [ 55 % ] of 107 ; group C : 40 [ 37 % ] of 108 ; group D : 60 [ 64 % ] of 94 ) , febrile neutropenia ( group A : 10 [ 9 % ] ; group B : 12 [ 11 % ] ; group C : 5 [ 5 % ] ; group D : 15 [ 16 % ] ) , and leucopenia ( group A : 13 [ 12 % ] ; group B : 6 [ 6 % ] ; group C : 4 [ 4 % ] ; group D : 8 [ 9 % ] ) . The number of patients with one or more serious adverse event was similar across groups ( 19 - 22 serious adverse events per group in 18 - 22 % of patients ) . INTERPRETATION Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs , but support the primary endpoint ( pathological complete response ) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel . Additionally , they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer . FUNDING F Hoffmann-La Roche BACKGROUND Previous results suggest that docetaxel plus cyclophosphamide improves disease-free survival ( DFS ) and overall survival compared with doxorubicin plus cyclophosphamide in early stage breast cancer . We assessed the addition of 1 year of trastuzumab to a non-anthracycline regimen , docetaxel plus cyclophosphamide , in patients with HER2-amplified early stage breast cancer and examined whether this regimen was equally effective in patients with TOP2A-amplified and TOP2A-non-amplified disease . METHODS This was an open-label , single-group , phase 2 study . El 
    Output:
    
Compared to shorter treatment duration s , there is sufficient evidence that 12 months of trastuzumab yields higher odds for the occurrence of relevant cardiac events .