***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 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 . BACKGROUND Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer . In this study , we compared 12 versus 6 months of adjuvant trastuzumab . PATIENTS AND METHODS Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were r and omized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense , granulocyte colony-stimulating factor (G-CSF)-supported docetaxel ( 75 mg/m(2 ) every 14 days for four cycles ) . All patients received upfront dose-dense , G-CSF-supported FEC ( 5-fluorouracil 700 mg/m(2 ) , epirubicin 75 mg/m(2 ) , cyclophosphamide 700 mg/m(2 ) every 14 days for four cycles ) . R and omization was carried out before commence of chemotherapy . The primary end point was the 3-year disease-free survival ( DFS ) . RESULTS A total of 481 patients were r and omized to receive 12 months ( n = 241 ) or 6 months ( n = 240 ) of adjuvant trastuzumab . Chemotherapy was completed in 99 % and 98 % of patients , while trastuzumab therapy in 100 % and 96 % of patients in the 12- and 6-month groups , respectively . After 47 and 51 months of median follow-up , there were 17 ( 7.1 % ) and 28 ( 11.7 % ) disease relapses in the 12- and 6-month groups ( P = 0.08 ) . The 3-year DFS was 95.7 % versus 93.3 % in favor of the 12-month treatment group ( hazard ratio = 1.57 ; 95 % confidence interval 0.86 - 2.10 ; P = 0.137 ) . There was no difference in terms of overall survival and cardiac toxicity between the two groups . CONCLUSIONS Our study failed to show noninferiority for the 6-month arm . The results further support the current st and ard of care that is administration of adjuvant trastuzumab for 12 months BACKGROUND ExteNET showed that 1 year of neratinib , an irreversible pan-HER tyrosine kinase inhibitor , significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer . We report up date d efficacy outcomes from a protocol -defined 5-year follow-up sensitivity analysis and long-term toxicity findings . METHODS In this ongoing r and omised , double-blind , placebo-controlled , phase 3 trial , eligible women aged 18 years or older ( ≥20 years in Japan ) with stage 1 - 3c ( modified to stage 2 - 3c in February , 2010 ) operable breast cancer , who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry . Patients who were eligible patients were r and omly assigned ( 1:1 ) via permuted blocks stratified according to hormone receptor status ( hormone receptor-positive vs hormone receptor-negative ) , nodal status ( 0 vs 1 - 3 vs or ≥4 positive nodes ) , and trastuzumab adjuvant regimen ( given sequentially vs concurrently with chemotherapy ) , then implemented central ly via an interactive voice and web-response system , to receive 1 year of oral neratinib 240 mg/day or matching placebo . Treatment was given continuously for 1 year , unless disease recurrence or new breast cancer , intolerable adverse events , or consent withdrawal occurred . Patients , investigators , and trial funder were masked to treatment allocation . The predefined endpoint of the 5-year analysis was invasive disease-free survival , analysed by intention to treat . ExteNET is registered with Clinical Trials.gov , number NCT00878709 , and is closed to new participants . FINDINGS Between July 9 , 2009 , and Oct 24 , 2011 , 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and r and omly assigned to receive neratinib ( n=1420 ) or placebo ( n=1420 ) . After a median follow-up of 5·2 years ( IQR 2·1 - 5·3 ) , patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group ( 116 vs 163 events ; stratified hazard ratio 0·73 , 95 % CI 0·57 - 0·92 , p=0·0083 ) . The 5-year invasive disease-free survival was 90·2 % ( 95 % CI 88·3 - 91·8 ) in the neratinib group and 87·7 % ( 85·7 - 89·4 ) in the placebo group . Without diarrhoea prophylaxis , the most common grade 3 - 4 adverse events in the neratinib group , compared with the placebo group , were diarrhoea ( 561 [ 40 % ] grade 3 and one [ < 1 % ] grade 4 with neratinib vs 23 [ 2 % ] grade 3 with placebo ) , vomiting ( grade 3 : 47 [ 3 % ] vs five [ < 1 % ] ) , and nausea ( grade 3 : 26 [ 2 % ] vs two [ < 1 % ] ) . Treatment-emergent serious adverse events occurred in 103 ( 7 % ) women in the neratinib group and 85 ( 6 % ) women in the placebo group . No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo . INTERPRETATION At the 5-year follow-up , 1 year of extended adjuvant therapy with neratinib , administered after chemotherapy and trastuzumab , significantly reduced the proportion of clinical ly relevant breast cancer relapses-ie , those that might lead to death , such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity . An analysis of overall survival is planned after 248 events . FUNDING Wyeth , Pfizer , and Puma Biotechnology BACKGROUND Trastuzumab , a recombinant monoclonal antibody against HER2 , has clinical activity in advanced breast cancer that overexpresses HER2 . We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy . METHODS This international , multicenter , r and omized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy .  RESULTS Data were available for 1694 women r and omly assigned to two years of treatment with trastuzumab , 1694 women assigned to one year of trastuzumab , and 1693 women assigned to observation .  We report here the results only of treatment with trastuzumab for one year or observation . At the first planned interim analysis ( median follow-up of one year ) , 347 events ( recurrence of breast cancer , contralateral breast cancer , second nonbreast malignant disease , or death ) were observed : 127 events in the trastuzumab group and 220 in the observation group . The unadjusted hazard ratio for an event in the trastuzumab group , as compared with the observation group , was 0.54 ( 95 percent confidence interval , 0.43 to 0.67 ; P<0.0001 by the log-rank test , crossing the interim analysis boundary ) , representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points . Overall survival in the two groups was not significantly different ( 29 deaths with trastuzumab vs. 37 with observation ) . Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab . CONCLUSIONS One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer . ( Clinical Trials.gov number , NCT00045032 . BACKGROUND We compared docetaxel with vinorelbine for the adjuvant treatment of early breast cancer . Women with tumors that overexpressed HER2/neu were also assigned to receive concomitant treatment with trastuzumab or no such treatment . METHODS We r and omly assigned 1010 women with axillary-node-positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine , followed by ( in both groups ) three cycles of fluorouracil , epirubicin , and cyclophosphamide . The 232 women whose tumors had an amplified HER2/neu gene were further assigned to receive or not to receive nine weekly trastuzumab infusions . The primary end point was recurrence-free survival . RESULTS Recurrence-free survival at three years was better with docetaxel than with vinorelbine ( 91 percent vs. 86 percent ; hazard ratio for recurrence or death , 0.58 ; 95 percent confidence interval , 0.40 to 0.85 ; P=0.005 ) , but overall survival did not differ between the groups ( P=0.15 ) . Within the subgroup of patients who had HER2/neu-positive cancer , those who received trastuzumab had better three-year recurrence-free survival than those who did not receive the antibody ( 89 percent vs. 78 percent ; hazard ratio for recurrence or death , 0.42 ; 95 percent confidence interval , 0.21 to 0.83 ; P=0.01 ) . Docetaxel was associated with more adverse effects than was vinorelbine . Trastuzumab was not associated with decreased left ventricular ejection fraction or cardiac failure . CONCLUSIONS Adjuvant treatment with docetaxel , as compared with vinorelbine , improves recurrence-free survival in women with early breast cancer . A short course of trastuzumab administered concomitantly with docetaxel or vinorelbine is effective in women with breast cancer who have an amplified HER2/neu gene . ( International St and ard R and omised Controlled Trial number , IS RCT N76560285 . ) BACKGROUND Since 2005 , 12 months of adjuvant trastuzumab has been the st and ard treatment for patients with HER2-positive early-stage breast cancer . However , the optimum duration of treatment has been debated . We did a non-inferiority trial of a shorter exposure of 6 months versus the st and ard 12 months of trastuzumab for patients with early breast cancer . METHODS We did an open-label , r and omised , phase 3 trial in 156 centres 
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In the subgroup analysis , there was a trend towards better DFS with the 1-year duration for patients with high-risk features , and also for concomitant administration of chemotherapy and trastuzumab .
Conclusions One-year adjuvant trastuzumab is associated with better DFS and OS compared with shorter duration s and should still be considered the st and ard duration .
However , selected patients with low-risk HER2 + BC can most likely be spared from an excess of cardiac toxicity with a shorter course