human
***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: 548 Background : Gene expression profiling may predict for pathologic complete response ( pCR ) after neoadjuvant therapy ( NT ) . Identification of both miRNA and gene expression may yield novel targets and improved NT . METHODS Patients ( pts ) with HER2- locally advanced/inflammatory breast cancer ( BC ) were r and omized to receive docetaxel , doxorubicin , cyclophosphamide ( TAC , arm A ) , or A and C given every 2 weeks × 4 , followed by carboplatin and nab-paclitaxel ( arm B ) . Pts with HER2 + BC received NT similar to arm B , with trastuzumab ( arm C ) . Core biopsies were snap-frozen prior to NT , and RNA was extracted for gene array analysis ( MammaPrint , BluePrint : basal , luminal , and HER2 profiling , and Agilent 44 K microarray ) , and for deep sequence miRNA analysis with the Solexa/Illumina platform . Pathological assessment included grade , ER , HER2 expression , and evidence of residual BC vs.pCR . Unsupervised hierarchical clustering analysis and Fisher 's exact tests were utilized to assess for correlation between miRNA and gene expression , and pathologic assessment . Significant analysis of microarrays ( SAM ) was used to identify miRNAs differentially expressed and predictive for response ( pCR vs. other ) to NT . RESULTS miRNA expression was measured in 72 of 119 enrolled pts ; 487 of the 882 miRNAs sequenced , were expressed with raw counts of > 10 in at least 3 pts . miRNA expression patterns revealed three distinct pt clusters , which were significantly associated with the 3 BluePrint subtypes and ER status ( Fisher 's exact test , P-values < 1e-5 ) , and moderately associated with HER2 status and MammaPrint classes at borderline significance ( P-value : 0.08 and 0.05 ) . SAM identified 6 up and 9 down-regulated miRNAs associated with pCR in HER2- patients ( N=43 , 4 pCRs ) with ≥2 fold changes at false discovery rate ( FDR ) < 10 % . No significant signals of miRNA expression associated with pCR were found in HER2 + pts ( N=28 ; 13 pCRs ) at the same FDR level . CONCLUSIONS Combined assessment of miRNA and gene expression patterns is feasible , and pending validation , may yield information leading to individualized and improved NT 136 Background : Nanoparticle Albumin-Bound Paclitaxel ( nab-PTX ) is a new solvent free taxane-based anticancer drug . According to CA024 trial , nab-PTX 100mg/m2 demonstrated superior response to docetaxel ( DTX ) in patients with metastatic breast cancer . Besides , nab-PTX 100mg/m2 was less toxicity . In operable breast cancer , GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel . We planned the r and omized parallel design phase II trial to evaluate nab-PTX 100mg/m2 in early breast cancer . METHODS Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX ( 75 mg/m2 day1 ) q 3 w or 4 cycles of nab-PTX ( 100 mg/m2 day1/8/15 ) q4w followed by 4 cycles of FE100C . The primary end point is pCR ( ypT0/is ypN0 ) rate , and the secondary end points are response rate , histological effect of treatment , breast conservation rate , and toxicity . RESULTS Between March 2011 to March 2014 , 152 eligible patients were enrolled at 6 centers ( 75 pts were allocated for nab-PTX ) . Baseline characteristics were well balanced ; median age was 51/49 years ( DTX/nab-PTX ) , 61/61 % of the patients with ER positive , 38/36 % triple negative breast cancer , 57/65 % Ki67 > 20 % . Clinical ly response rate was similar to each drug . ( 53/57 % ) The pCR rate was 12/17 % ( p = 0.323 ) . In TNBC group , the pCR rate was 28/30 % ( p = 0.866 ) . In Ki67 > 20 % group , the pCR rate was significantly higher , 16/48 % ( p = 0.021 ) with nab-PTX arm . The most common grade 3 - 4 adverse event was neutropenia , which was observed in 40/36 % of cases . Non-hematological adverse events of any grade were ; 34/32 % myalgia ( DTX/nab-PTX ) , 42/35 % arthralgia , 55/65 % peripheral sensory neuropathy . No Grade 3 - 4 peripheral sensory neuropathy was observed in nab-PTX arm . Infusion reaction of DTX occurred in 1 patient . CONCLUSIONS In this initial effectively analysis , neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients . Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX . CLINICAL TRIAL INFORMATION 000005388 BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined .  Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background Neoadjuvant chemotherapy has become st and ard treatment for women with locally advanced breast cancer . The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel ( nab-paclitaxel ) versus paclitaxel combined with carboplatin . Methods Thirty patients were treated with neoadjuvant nab-paclitaxel ( 125 mg/m2 , days 1 , 8 , and 15 ) and carboplatin ( area under the curve = 2 ; days 1 , 8 , and 15 ) every 21 days for four cycles . Ninety matched patients received paclitaxel ( 80 mg/m2 , days 1 , 8 , and 15 ) and carboplatin every 21 days for four cycles . Weekly trastuzumab is recommended for overexpression of human epidermal receptor-2 . The primary endpoint was pathologic complete response ( defined as ypT0/is ypN0 ) . Matching was conducted according to six variables : body mass index , clinical tumor stage , clinical lymph node status , estrogen receptor status , HER2 status , and trastuzumab receiving rate . Results Ninety percent of patients in the nab-paclitaxel group and 80 % of patients in the paclitaxel group experienced a clinical objective response ( complete response or partial response ; P=0.450 ) . Eight patients in the nab-paclitaxel group and 23 patients in the paclitaxel group had a pathologic complete response in the breast and axillary nodes ( 26.7 % versus 25.6 % ; P=0.904 ) . Nab-paclitaxel showed a beneficial effective trend on clinical tumor stage II ( 36.8 % versus 15.8 % ; P=0.051 ) . When trastuzumab was added to nab-paclitaxel , the pathologic complete response rate was not significantly improved more than with trastuzumab and paclitaxel ( 43.6 % versus 39.6 % ; P=0.769 ) . Carboplatin plus nab-paclitaxel or paclitaxel had similarly low pathologic complete response rates ( 7.7 % versus 10.5 % ) for the luminal molecular subtype . One ( 50 % ) triple-negative patient achieved a pathologic complete response . The nab-paclitaxel regimen caused more grade 4 neutropenia than the paclitaxel regimen ( 56.7 % versus 21.1 % ; P<0.001 ) . Conclusion Our study shows that weekly nab-paclitaxel and carboplatin with or without trastuzumab result ed in a pathologic complete response rate that was not superior to the matched cohorts . Future , larger trials are needed to vali date that nab-paclitaxel is beneficial for clinical tumor stage II and the triple-negative subgroup SWOG S0800 , a r and omized open-label Phase II clinical trial , compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide ( AC ) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer ( LABC ) or inflammatory breast cancer ( IBC ) . Patients were r and omly allocated ( 2:1:1 ) to three neoadjuvant chemotherapy arms : ( 1 ) nab-paclitaxel with concurrent bevacizumab followed by AC ; ( 2 ) nab-paclitaxel followed by AC ; or ( 3 ) AC followed by nab-paclitaxel . The primary endpoint was pathologic complete response ( pCR ) with stratification by disease type ( non-IBC LABC vs. IBC ) and hormone receptor status ( positive vs. negative ) . Overall survival ( OS ) , event-free survival ( EFS ) , and toxicity were secondary endpoints . Analyses were intent-to-treat comparing bevacizumab to the combined control arms . A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer ( TNBC ) . The addition of bevacizumab significantly increased the pCR 
    Output:
    
agent
***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: 548 Background : Gene expression profiling may predict for pathologic complete response ( pCR ) after neoadjuvant therapy ( NT ) . Identification of both miRNA and gene expression may yield novel targets and improved NT . METHODS Patients ( pts ) with HER2- locally advanced/inflammatory breast cancer ( BC ) were r and omized to receive docetaxel , doxorubicin , cyclophosphamide ( TAC , arm A ) , or A and C given every 2 weeks × 4 , followed by carboplatin and nab-paclitaxel ( arm B ) . Pts with HER2 + BC received NT similar to arm B , with trastuzumab ( arm C ) . Core biopsies were snap-frozen prior to NT , and RNA was extracted for gene array analysis ( MammaPrint , BluePrint : basal , luminal , and HER2 profiling , and Agilent 44 K microarray ) , and for deep sequence miRNA analysis with the Solexa/Illumina platform . Pathological assessment included grade , ER , HER2 expression , and evidence of residual BC vs.pCR . Unsupervised hierarchical clustering analysis and Fisher 's exact tests were utilized to assess for correlation between miRNA and gene expression , and pathologic assessment . Significant analysis of microarrays ( SAM ) was used to identify miRNAs differentially expressed and predictive for response ( pCR vs. other ) to NT . RESULTS miRNA expression was measured in 72 of 119 enrolled pts ; 487 of the 882 miRNAs sequenced , were expressed with raw counts of > 10 in at least 3 pts . miRNA expression patterns revealed three distinct pt clusters , which were significantly associated with the 3 BluePrint subtypes and ER status ( Fisher 's exact test , P-values < 1e-5 ) , and moderately associated with HER2 status and MammaPrint classes at borderline significance ( P-value : 0.08 and 0.05 ) . SAM identified 6 up and 9 down-regulated miRNAs associated with pCR in HER2- patients ( N=43 , 4 pCRs ) with ≥2 fold changes at false discovery rate ( FDR ) < 10 % . No significant signals of miRNA expression associated with pCR were found in HER2 + pts ( N=28 ; 13 pCRs ) at the same FDR level . CONCLUSIONS Combined assessment of miRNA and gene expression patterns is feasible , and pending validation , may yield information leading to individualized and improved NT 136 Background : Nanoparticle Albumin-Bound Paclitaxel ( nab-PTX ) is a new solvent free taxane-based anticancer drug . According to CA024 trial , nab-PTX 100mg/m2 demonstrated superior response to docetaxel ( DTX ) in patients with metastatic breast cancer . Besides , nab-PTX 100mg/m2 was less toxicity . In operable breast cancer , GeparSepto study was reported that the pCR rate were significantly higher with nab-PTX 125/150 mg/m2 compared to paclitaxel . We planned the r and omized parallel design phase II trial to evaluate nab-PTX 100mg/m2 in early breast cancer . METHODS Stage II-III HER2-negative breast cancer patients were included in this trial and received either 4 cycles of DTX ( 75 mg/m2 day1 ) q 3 w or 4 cycles of nab-PTX ( 100 mg/m2 day1/8/15 ) q4w followed by 4 cycles of FE100C . The primary end point is pCR ( ypT0/is ypN0 ) rate , and the secondary end points are response rate , histological effect of treatment , breast conservation rate , and toxicity . RESULTS Between March 2011 to March 2014 , 152 eligible patients were enrolled at 6 centers ( 75 pts were allocated for nab-PTX ) . Baseline characteristics were well balanced ; median age was 51/49 years ( DTX/nab-PTX ) , 61/61 % of the patients with ER positive , 38/36 % triple negative breast cancer , 57/65 % Ki67 > 20 % . Clinical ly response rate was similar to each drug . ( 53/57 % ) The pCR rate was 12/17 % ( p = 0.323 ) . In TNBC group , the pCR rate was 28/30 % ( p = 0.866 ) . In Ki67 > 20 % group , the pCR rate was significantly higher , 16/48 % ( p = 0.021 ) with nab-PTX arm . The most common grade 3 - 4 adverse event was neutropenia , which was observed in 40/36 % of cases . Non-hematological adverse events of any grade were ; 34/32 % myalgia ( DTX/nab-PTX ) , 42/35 % arthralgia , 55/65 % peripheral sensory neuropathy . No Grade 3 - 4 peripheral sensory neuropathy was observed in nab-PTX arm . Infusion reaction of DTX occurred in 1 patient . CONCLUSIONS In this initial effectively analysis , neoadjuvant weekly nab-paclitaxel 100mg/m2 were promising drug in HER2-negative operable breast cancer patients . Larger studies will be needed to evaluate neoadjuvant weekly nab-paclitaxel compared with DTX . CLINICAL TRIAL INFORMATION 000005388 BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined .  Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background Neoadjuvant chemotherapy has become st and ard treatment for women with locally advanced breast cancer . The aim of this study was to compare the efficacy and safety of nanoparticle albumin-bound paclitaxel ( nab-paclitaxel ) versus paclitaxel combined with carboplatin . Methods Thirty patients were treated with neoadjuvant nab-paclitaxel ( 125 mg/m2 , days 1 , 8 , and 15 ) and carboplatin ( area under the curve = 2 ; days 1 , 8 , and 15 ) every 21 days for four cycles . Ninety matched patients received paclitaxel ( 80 mg/m2 , days 1 , 8 , and 15 ) and carboplatin every 21 days for four cycles . Weekly trastuzumab is recommended for overexpression of human epidermal receptor-2 . The primary endpoint was pathologic complete response ( defined as ypT0/is ypN0 ) . Matching was conducted according to six variables : body mass index , clinical tumor stage , clinical lymph node status , estrogen receptor status , HER2 status , and trastuzumab receiving rate . Results Ninety percent of patients in the nab-paclitaxel group and 80 % of patients in the paclitaxel group experienced a clinical objective response ( complete response or partial response ; P=0.450 ) . Eight patients in the nab-paclitaxel group and 23 patients in the paclitaxel group had a pathologic complete response in the breast and axillary nodes ( 26.7 % versus 25.6 % ; P=0.904 ) . Nab-paclitaxel showed a beneficial effective trend on clinical tumor stage II ( 36.8 % versus 15.8 % ; P=0.051 ) . When trastuzumab was added to nab-paclitaxel , the pathologic complete response rate was not significantly improved more than with trastuzumab and paclitaxel ( 43.6 % versus 39.6 % ; P=0.769 ) . Carboplatin plus nab-paclitaxel or paclitaxel had similarly low pathologic complete response rates ( 7.7 % versus 10.5 % ) for the luminal molecular subtype . One ( 50 % ) triple-negative patient achieved a pathologic complete response . The nab-paclitaxel regimen caused more grade 4 neutropenia than the paclitaxel regimen ( 56.7 % versus 21.1 % ; P<0.001 ) . Conclusion Our study shows that weekly nab-paclitaxel and carboplatin with or without trastuzumab result ed in a pathologic complete response rate that was not superior to the matched cohorts . Future , larger trials are needed to vali date that nab-paclitaxel is beneficial for clinical tumor stage II and the triple-negative subgroup SWOG S0800 , a r and omized open-label Phase II clinical trial , compared the combination of weekly nab-paclitaxel and bevacizumab followed by dose-dense doxorubicin and cyclophosphamide ( AC ) with nab-paclitaxel followed or preceded by AC as neoadjuvant treatment for HER2-negative locally advanced breast cancer ( LABC ) or inflammatory breast cancer ( IBC ) . Patients were r and omly allocated ( 2:1:1 ) to three neoadjuvant chemotherapy arms : ( 1 ) nab-paclitaxel with concurrent bevacizumab followed by AC ; ( 2 ) nab-paclitaxel followed by AC ; or ( 3 ) AC followed by nab-paclitaxel . The primary endpoint was pathologic complete response ( pCR ) with stratification by disease type ( non-IBC LABC vs. IBC ) and hormone receptor status ( positive vs. negative ) . Overall survival ( OS ) , event-free survival ( EFS ) , and toxicity were secondary endpoints . Analyses were intent-to-treat comparing bevacizumab to the combined control arms . A total of 215 patients were accrued including 11 % with IBC and 32 % with triple-negative breast cancer ( TNBC ) . The addition of bevacizumab significantly increased the pCR 
    Output:
    