***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 : Recent UK clinical guidance advises against continuing trastuzumab ( T ) beyond disease progression ( PD ) in the absence of brain metastases in patients with HER-2 positive ( + ve ) advanced breast cancer .We have retrospectively evaluated the outcome of patients with HER-2+ve locally advanced ( LA ) or metastatic breast cancer ( MBC ) who continued T beyond PD , treated in our unit . Methods : All HER-2+ve patients on our prospect ively maintained data base with LA or MBC who received T beyond PD after adjuvant or one line of T for advanced disease were assessed for response and outcome . From the timepoint of T continuation beyond PD , we calculated the overall disease control rate , time to progression ( TTP ) , and overall survival ( OS ) . Results : One hundred and fourteen patients with HER-2+ve LA or MBC treated with T beyond PD were identified . The main site of disease was visceral_in 84 ( 74 % ) patients . Seventy-six ( 66 % ) had one line of chemotherapy before continuation of T beyond PD and 21 ( 19 % ) had two or more . Post-progression , 66 ( 58 % ) received T combined with chemotherapy . Of the 93 ( 82 % ) patients with documented clinical or radiological response evaluation , 67 ( 59 % ) were considered as having stable disease or better . The median TTP was 24 weeks ( 95 % CI : 21–28 ) and the median OS was 19 months ( 95 % CI : 12–24 ) . Conclusion : Our results from an unselected group of patients provide additional evidence that continuation of T beyond PD is of clinical benefit Background Combining trastuzumab and chemotherapy is st and ard in her2/neu overexpressing advanced breast cancer . It is not established however , whether trastuzumab treatment should continue after the failure of one earlier combination . In this trial , we report our experience with continued treatment beyond disease progression . Methods Fifty-four patients , median age 46 years , range 25–73 years , were included . We analysed for time to tumour progression ( TTP ) for first , second and beyond second line treatment , response rates and overall survival . Results Median time of observation was 24 months , range 7–51 . Response rates for first line treatment were 7.4 % complete remission ( CR ) , 35.2 % partial remissions ( PR ) , 42.6 % stable disease > 6 months ( SD ) and 14.8 % of patients experienced disease progression despite treatment ( PD ) . Corresponding numbers for second line were 3.7 % CR , 22.2 % PR , 42.6 % SD and 31.5 % PD ; numbers for treatment beyond second line ( 60 therapies , 33 pts 3rd line , 18 pts 4th line , 6 pts 5th line , 2 pts 6th line and 1 patient 7th line ) were 1.7 % CR , 28.3 % PR , 28.3 % SD and 41.6 % PD respectively . Median TTP was 6 months ( m ) in the first line setting , and also 6 m for second line and beyond second line . An asymptomatic drop of left ventricular ejection fraction below 50 % was observed in one patient . No case of symptomatic congestive heart failure was observed . Conclusion The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment . The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy . Still , r and omized trials are warranted HER2 overexpression is associated with poor breast cancer prognosis and is the target for the humanized monoclonal antibody trastuzumab . This novel agent , when administered until disease progression in combination with chemotherapy , extends the survival of women with HER2-positive metastatic breast cancer ( MBC ) . However , the optimal duration of trastuzumab therapy remains to be confirmed . We conducted a retrospective case review study of women with HER2-positive MBC who continued to receive trastuzumab beyond disease progression . Objectives were to assess whether treatment beyond disease progression shows any evidence of efficacy and to evaluate the feasibility of this approach . One hundred five patients ( median age , 47 years ; range , 24 - 77 years ) were identified in 13 centers . Women had received < /=6 chemotherapy regimens ( median , 1 ) before  trastuzumab therapy . Median survival from first trastuzumab dose was 29 months . The overall response rate to trastuzumab alone or with a taxane  as the first regimen was 39 % ; a further 30 % of patients had stable disease as the best response . These rates were 36 % and 38 % after a second regimen of trastuzumab alone or with paclitaxel or vinorelbine was administered . Some patients responded to both the first and second regimens ; others responded to the second regimen after the first had failed . Twenty-two patients experienced cardiac events , of whom 18 received > /=1 more trastuzumab regimen . Trastuzumab treatment beyond progression appears to be of value , producing responses and clinical benefit , and is well tolerated without significant cardiac toxicity . The feasibility of this approach warrants examination in prospect i ve trials Purpose Lapatinib is a small molecule , dual tyrosine kinase inhibitor of epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor type 2 ( HER2 ) . Initial results of a phase III trial demonstrated that lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab . Up date d efficacy and initial biomarker results from this trial are reported . Methods Women with HER2-positive , locally advanced or metastatic breast cancer previously treated with anthracycline- , taxane- , and trastuzumab-containing regimens were r and omized to lapatinib 1,250 mg/day continuously plus capecitabine 2,000 mg/m2 days 1–14 of a 21-day cycle or capecitabine 2,500 mg/m2 on the same schedule . The primary endpoint was time to progression ( TTP ) as determined by an independent review panel . Relationship between progression-free survival ( PFS ) and tumor HER2 expression and serum levels of HER2 extracellular domain ( ECD ) were assessed . Results 399 women were r and omized . The addition of lapatinib prolonged TTP with a hazard ratio ( HR ) of 0.57 ( 95 % CI , 0.43–0.77 ; P < 0.001 ) and provided a trend toward improved overall survival ( HR : 0.78 , 95 % CI : 0.55–1.12 , P = 0.177 ) , and fewer cases with CNS involvement at first progression ( 4 vs. 13 , P = 0.045 ) . Baseline serum HER2 ECD did not predict for benefit from lapatinib . Conclusion The addition of lapatinib to capecitabine provides superior efficacy for women with HER2-positive , advanced breast cancer progressing after treatment with anthracycline- ,  taxane- , and trastuzumab-based therapy . Biomarker studies could not identify a subgroup of patients who failed to benefit from the addition of lapatinib to capecitabine BACKGROUND Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab  can benefit from lapatinib , a dual epidermal growth factor receptor/HER2 tyrosine kinase ( TK ) inhibitor . Before the availability of this compound , trastuzumab was often continued beyond disease progression , usually in addition to further chemotherapy , an approach which was not based on r and omized studies . We sought to retrospectively compare the clinical outcomes of patients who , upon progression during an initial trastuzumab-based regimen , stopped or continued trastuzumab in addition to further chemotherapy . PATIENTS AND METHODS From the clinical records of 407 patients with HER2-positive advanced breast cancer , we identified 279 patients progressing during an initial trastuzumab-based treatment .  Of these patients , 83 continued trastuzumab in addition to chemotherapy , and 112 received chemotherapy alone . RESULTS We found no difference in response rate ( 28 % vs. 30 % ; P = .5 ) , median time to second tumor progression ( 8.4 months vs. 7 months ; P = .24 ) , or median postprogression survival ( 20.6 months and 15.4 months ; P = .29 ) according to whether patients continued or stopped trastuzumab . At multivariate analysis , continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression ( hazard ratio , 0.753 ; P = .08 ) . CONCLUSION Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy . For these patients , there is evidence from a large r and omized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib PURPOSE To evaluate the efficacy and safety of weekly paclitaxel and trastuzumab in patients with HER2-positive metastatic breast cancer , with trastuzumab administered beyond disease progression . PATIENTS AND METHODS Twenty-six women with metastatic breast cancer , that was HER2-positive as determined by immunohistochemistry , were treated with weekly paclitaxel 70 or 90 mg/m2 and trastuzumab ( 4 mg/kg initial dose followed by 2 mg/kg weekly ) . RESULTS The median duration of treatment was 28 ( 8 - 72 ) weeks for paclitaxel and 59 ( 14 - 150 ) weeks for trastuzumab . Two ( 8 % ) patients experienced complete and 14 ( 54 % ) partial responses , for an overall response rate of 62 % . The median time to disease progression was 11 ( 2.89 - 36 ) months and median survival 34 + months . Grade 3/4 adverse events were alopecia ( 46 % ) , neurotoxicity ( 15 % ) , leukopenia ( 12 % ) and neutropenia ( 12 % ) . Infusion-related reactions were mild to moderate . No symptomatic cardiac toxicity was observed . No patient discontinued trastuzumab due to toxicity . CONCLUSION Prolonged administration of weekly paclitaxel and trastuzumab is effective and well-tolerated in women with HER2-positive metastatic breast cancer BACKGROUND Continuation of trastuzumab plus capecitabine ( XH ) showed a significantly improved overall response rate and time to progression compared with capecitabine ( X ) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment . Here , we report the final analysis on overall survival . PATIENTS AND METHODS Patients with HER2-positive , advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy  were prospect ively r and omised to X ( 2500mg/m(2 ) on days 1 - 14 , q3w ) or XH ( 6 (8)mg/kg , q3w ) . Overall survival was a pre-specified secondary end-point . RESULTS Median follow-up at June 2010 was 20.7months . Fifty nine of 74 and 60 of 77 patients died in the X and XH arm , respectively . Median overall survival was 20.6 and 24.9months with X and XH , respectively ( HR=0.94 [ 0.65 - 1.35 ] ; p=0.73 ) . Performance status and metastatic site were independent prognosticators for overall survival . No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit , respectively . Patients who continued/restarted anti-HER2 treatment ( trastuzumab or lapatinib ) after 2nd progression ( N=52 ) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents ( N=88 ) ( HR 0.63 ; p=0.02 ) . CONCLUSIONS Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab . However , in a post-hoc analysis , patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment BACKGROUND Trastuzumab emtansine ( T-DM1 ) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1 . The antibody and the cytotoxic agent are conjugated by means of a stable linker . METHODS We r and omly assigned patients with HER2-positive advanced breast cancer , who had previously been treated with trastuzumab and a taxane , to T-DM1 or lapatinib plus capecitabine .  The primary end points were progression-free survival ( as assessed by independent review ) , overall survival , and safety . Secondary end points included progression-free survival ( 
    Output:
    
This pooled analysis confirms that continuing T beyond the first progression continues to be 1 of the effective and preferred choices in HER2 + MBC , failing a ( T-based ) first-line regimen