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: Background Pathological complete response ( pCR ) is associated with improved prognosis in triple-negative breast cancer ( TNBC ) . The optimal chemotherapy regimen is unclear . Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact . We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response . Methods Patients with TNBC ( estrogen receptor/progesterone receptor < 1 % , human epidermal growth factor receptor 2-negative , cT1c-cT4c , cN0/+ ) were r and omly assigned to A : nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly ( q3w ) ; vs B : nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w . The trial was powered for a pCR ( ypT0/is ypN0 ) comparison by therapy arm and early response ( defined as Ki-67 decrease > 30 % or < 500 invasive tumor cells in the three-week serial biopsy ) . All statistical tests were two-sided . Results A total of 336 patients were enrolled ( 48 centers , arms A/B : n = 182/154 ) . The median age was 50 years . At baseline ( A vs B ) , 62.6 % and 62.9 % had cT2 - 4c tumors ; 86.8 % and 90.9 % completed therapy per protocol , respectively . pCR favored arm B ( 28.7 % , 95 % CI = 0.22 to 0.36 , vs 45.9 % , 95 % CI = 0.38 to 0.54 ; 95 % CI(dBA ) = 6.2 % to 27.9 % , P = .002 ) and was lower in nonresponders than in early responders ( 19.5 % vs 44.4 % , P < .001 ) or in patients with unclassifiable early response ( 50.0 % ) . The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions ( 20.6 % vs 11.9 % , P = .04 ) , treatment-related serious adverse events ( 11.1 % vs 5.3 % , P = .07 ) , grade 3 - 4 infections ( 7.2 % vs 2.6 % , P = .07 ) , and grade 3 - 4 ALAT elevations ( 11.7 vs 3.3 % , P = .01 ) . Conclusions This first large r and omized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/carboplatin regimen , superior to nab-paclitaxel/gemcitabine in TNBC . De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research . Early necrotic morphological changes and /or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR Background : No st and ard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer ( TNBC ) . This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy ( NAC ) in TNBC . Results : 91 patients with a median age of 47 years ( PC 47 patients , EP 44 patients ) were enrolled . 65 % of the patients were premenopausal . While the objective response rate was similar in the PC and EP arm ( 89.4 % vs. 79.5 % , P = 0.195 ) , the pCR rate in the PC arm was significantly higher ( 38.6 % vs. 14.0 % , P = 0.014 ) . The median follow-up time was 55.0 months . 5-year RFS were 77.6 % and 56.2 % , significantly higher in the PC arm , P = 0.043 . No significant difference in OS was observed between the two arms ( P = 0.350 ) . Adverse events were similar , except for more thrombocytopenia in the PC arm ( P = 0.001 ) . Methods : Patients with stage II/III TNBC were r and omized to receive either paclitaxel ( 175 mg/m2 , day1 ) plus carboplatin ( Area Under the Curve = 5 , day2 ) ( PC ) or epirubicin ( 75mg/m2 , day1 ) plus paclitaxel ( 175 mg/m2 , day2 ) ( EP ) as NAC every three weeks for 4 - 6 cycles . The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival ( RFS ) , overall survival ( OS ) and safety . Conclusions : This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS . Further phase 3 study has already started Germline mutations in BRCA1/2 predispose individuals to breast cancer ( termed germline-mutated BRCA1/2 breast cancer , gBRCA-BC ) by impairing homologous recombination ( HR ) and causing genomic instability . HR also repairs DNA lesions caused by platinum agents and PARP inhibitors . Triple-negative breast cancers ( TNBCs ) harbor sub population s with BRCA1/2 mutations , hypothesized to be especially platinum-sensitive . Cancers in putative ‘ BRCAness ’ subgroups — tumors with BRCA1 methylation ; low levels of BRCA1 mRNA ( BRCA1 mRNA-low ) ; or mutational signatures for HR deficiency and those with basal phenotypes — may also be sensitive to platinum . We assessed the efficacy of carboplatin and another mechanistically distinct therapy , docetaxel , in a phase 3 trial in subjects with unselected advanced TNBC . A prespecified protocol enabled biomarker – treatment interaction analyses in gBRCA-BC and BRCAness subgroups . The primary endpoint was objective response rate ( ORR ) . In the unselected population ( 376 subjects ; 188 carboplatin  , 188 docetaxel )  , carboplatin was not more active than docetaxel ( ORR , 31.4 % versus 34.0 % , respectively ; P = 0.66 ) . In contrast , in subjects with gBRCA-BC , carboplatin had double the ORR of docetaxel ( 68 % versus 33 % , respectively ; biomarker , treatment interaction P = 0.01 ) . Such benefit was not observed for subjects with BRCA1 methylation , BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay . Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup . We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations , but not BRCA1 methylation or Myriad HRD analyses , to inform choices on platinum-based chemotherapy . Additionally , gene expression analysis of basal-like cancers may also influence treatment selection .The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer ( BC ) patients . Pre clinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no r and omized study supporting this hypothesis . This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context . Patients with operable breast cancer and immunophenotypically defined basal-like disease ( ER-/PR-/HER2- and cytokeratin 5/6 + or EGFR+ ) were recruited . Patients were r and omized to receive EC ( epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 for 4 cycles ) followed either by D ( docetaxel 100 mg/m2 × 4 cycles ; EC – D ) or DCb ( docetaxel 75 mg/m2 plus carboplatin AUC 6 × 4 cycles ; EC – DCb ) . The primary end point was pathological complete response ( pCR ) in the breast following the Miller and Payne criteria . Ninety-four patients were r and omized ( 46 EC – D , 48 EC – DCb ) . pCR rate in the breast was seen in 16 patients ( 35 % ) with EC – D and 14 patients ( 30 % ) with EC – DCb ( P value = 0.61 ) . pCR in the breast and axilla was seen in 30 % of patients in both arms . The overall clinical response rate was 70 % ( 95 % CI 56–83 ) in the EC – D arm and 77 % ( 95 % CI 65–87 ) in the EC – DCb arm . Grade 3/4 toxicity was similar in both arms . The addition of carboplatin to conventional chemotherapy with EC – D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent . These findings should be taken into consideration when developing new agents for this disease Abstract Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response ( pCR ) rates . We evaluated the efficacy and safety of carboplatin and weekly paclitaxel ( wPTX ) followed by cyclophosphamide , epirubicin , and 5-fluorouracil ( CEF ) as neoadjuvant chemotherapy for HER2-negative breast cancer . Patients with stage II/IIIA HER2-negative breast cancer were r and omly assigned to preoperatively receive CP-CEF ( four 3-week cycles of carboplatin [ area under the curve 5 mg/mL/min , day 1 ] and wPTX [ 80 mg/m2 , day 1 , 8 , 15 ] followed by four 3-week cycles of CEF [ 500/100/500 mg/m2 ] or P-CEF ( four cycles of wPTX followed by four cycles of CEF ) . The primary objective was pCR rate .  Of 181 eligible patients , 89 were r and omly assigned to the  CP-CEF  and 92 to the P-CEF . Two patients in each arm refused to receive neoadjuvant chemotherapy . Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety . The pCR rate in the CP-CEF was significantly higher than that in the P-CEF ( 31.8 vs. 17.6 % , one-sided P = 0.01 ) . Among patients with triple-negative breast cancer , the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [ 61.2 ( 23/37 ) vs. 26.3 % ( 10/38 ) , P = 0.003 ] . Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF ( 65.9 vs. 38.5 % ) . Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity Purpose Docetaxel and cyclophosphamide ( TC ) was superior to doxorubicin and cyclophosphamide ( AC ) in a trial in early breast cancer . However , activity of TC relative to AC regimens with a taxane ( TaxAC ) is unknown . Methods In a series of three adjuvant trials , women were r and omly assigned to TC for six cycles ( TC6 ) or to a  st and ard TaxAC regimen .  US Oncology Research ( USOR ) 06 - 090 compared TC6 with docetaxel , doxorubicin , and cyclophosphamide ( TAC6 ) . National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-46-I/USOR 07132 compared TC6 , TAC6 , or TC6 plus bevacizumab . NSABP B-49 compared TC6 with several st and ard AC and taxane combination regimens . Before any analysis of individual trials , a joint efficacy analysis of TC versus the TaxAC regimens was planned , with invasive disease-free survival ( IDFS ) as the primary end point . Patients who received TC6 plus bevacizumab  on NSABP B-46-I/USOR 07132 were not included . A hazard ratio ( HR ) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6 . The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed ( 50 % of 668 events required for definitive analysis ) . Results A total of 2,125 patients were r and omly assigned to receive TC6 regimens and 2,117 patients were r and 
    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: Background Pathological complete response ( pCR ) is associated with improved prognosis in triple-negative breast cancer ( TNBC ) . The optimal chemotherapy regimen is unclear . Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact . We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response . Methods Patients with TNBC ( estrogen receptor/progesterone receptor < 1 % , human epidermal growth factor receptor 2-negative , cT1c-cT4c , cN0/+ ) were r and omly assigned to A : nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly ( q3w ) ; vs B : nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w . The trial was powered for a pCR ( ypT0/is ypN0 ) comparison by therapy arm and early response ( defined as Ki-67 decrease > 30 % or < 500 invasive tumor cells in the three-week serial biopsy ) . All statistical tests were two-sided . Results A total of 336 patients were enrolled ( 48 centers , arms A/B : n = 182/154 ) . The median age was 50 years . At baseline ( A vs B ) , 62.6 % and 62.9 % had cT2 - 4c tumors ; 86.8 % and 90.9 % completed therapy per protocol , respectively . pCR favored arm B ( 28.7 % , 95 % CI = 0.22 to 0.36 , vs 45.9 % , 95 % CI = 0.38 to 0.54 ; 95 % CI(dBA ) = 6.2 % to 27.9 % , P = .002 ) and was lower in nonresponders than in early responders ( 19.5 % vs 44.4 % , P < .001 ) or in patients with unclassifiable early response ( 50.0 % ) . The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions ( 20.6 % vs 11.9 % , P = .04 ) , treatment-related serious adverse events ( 11.1 % vs 5.3 % , P = .07 ) , grade 3 - 4 infections ( 7.2 % vs 2.6 % , P = .07 ) , and grade 3 - 4 ALAT elevations ( 11.7 vs 3.3 % , P = .01 ) . Conclusions This first large r and omized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/carboplatin regimen , superior to nab-paclitaxel/gemcitabine in TNBC . De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research . Early necrotic morphological changes and /or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR Background : No st and ard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer ( TNBC ) . This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy ( NAC ) in TNBC . Results : 91 patients with a median age of 47 years ( PC 47 patients , EP 44 patients ) were enrolled . 65 % of the patients were premenopausal . While the objective response rate was similar in the PC and EP arm ( 89.4 % vs. 79.5 % , P = 0.195 ) , the pCR rate in the PC arm was significantly higher ( 38.6 % vs. 14.0 % , P = 0.014 ) . The median follow-up time was 55.0 months . 5-year RFS were 77.6 % and 56.2 % , significantly higher in the PC arm , P = 0.043 . No significant difference in OS was observed between the two arms ( P = 0.350 ) . Adverse events were similar , except for more thrombocytopenia in the PC arm ( P = 0.001 ) . Methods : Patients with stage II/III TNBC were r and omized to receive either paclitaxel ( 175 mg/m2 , day1 ) plus carboplatin ( Area Under the Curve = 5 , day2 ) ( PC ) or epirubicin ( 75mg/m2 , day1 ) plus paclitaxel ( 175 mg/m2 , day2 ) ( EP ) as NAC every three weeks for 4 - 6 cycles . The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival ( RFS ) , overall survival ( OS ) and safety . Conclusions : This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS . Further phase 3 study has already started Germline mutations in BRCA1/2 predispose individuals to breast cancer ( termed germline-mutated BRCA1/2 breast cancer , gBRCA-BC ) by impairing homologous recombination ( HR ) and causing genomic instability . HR also repairs DNA lesions caused by platinum agents and PARP inhibitors . Triple-negative breast cancers ( TNBCs ) harbor sub population s with BRCA1/2 mutations , hypothesized to be especially platinum-sensitive . Cancers in putative ‘ BRCAness ’ subgroups — tumors with BRCA1 methylation ; low levels of BRCA1 mRNA ( BRCA1 mRNA-low ) ; or mutational signatures for HR deficiency and those with basal phenotypes — may also be sensitive to platinum . We assessed the efficacy of carboplatin and another mechanistically distinct therapy , docetaxel , in a phase 3 trial in subjects with unselected advanced TNBC . A prespecified protocol enabled biomarker – treatment interaction analyses in gBRCA-BC and BRCAness subgroups . The primary endpoint was objective response rate ( ORR ) . In the unselected population ( 376 subjects ; 188 carboplatin  , 188 docetaxel )  , carboplatin was not more active than docetaxel ( ORR , 31.4 % versus 34.0 % , respectively ; P = 0.66 ) . In contrast , in subjects with gBRCA-BC , carboplatin had double the ORR of docetaxel ( 68 % versus 33 % , respectively ; biomarker , treatment interaction P = 0.01 ) . Such benefit was not observed for subjects with BRCA1 methylation , BRCA1 mRNA-low tumors or a high score in a Myriad HRD assay . Significant interaction between treatment and the basal-like subtype was driven by high docetaxel response in the nonbasal subgroup . We conclude that patients with advanced TNBC benefit from characterization of BRCA1/2 mutations , but not BRCA1 methylation or Myriad HRD analyses , to inform choices on platinum-based chemotherapy . Additionally , gene expression analysis of basal-like cancers may also influence treatment selection .The phase 3 TNT Trial in subjects with triple-negative breast cancer supports the superiority of carboplatin over docetaxel in BRCA1/2-mutated tumors and a greater response to taxanes in the nonbasal subtype Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer ( BC ) patients . Pre clinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no r and omized study supporting this hypothesis . This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context . Patients with operable breast cancer and immunophenotypically defined basal-like disease ( ER-/PR-/HER2- and cytokeratin 5/6 + or EGFR+ ) were recruited . Patients were r and omized to receive EC ( epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 for 4 cycles ) followed either by D ( docetaxel 100 mg/m2 × 4 cycles ; EC – D ) or DCb ( docetaxel 75 mg/m2 plus carboplatin AUC 6 × 4 cycles ; EC – DCb ) . The primary end point was pathological complete response ( pCR ) in the breast following the Miller and Payne criteria . Ninety-four patients were r and omized ( 46 EC – D , 48 EC – DCb ) . pCR rate in the breast was seen in 16 patients ( 35 % ) with EC – D and 14 patients ( 30 % ) with EC – DCb ( P value = 0.61 ) . pCR in the breast and axilla was seen in 30 % of patients in both arms . The overall clinical response rate was 70 % ( 95 % CI 56–83 ) in the EC – D arm and 77 % ( 95 % CI 65–87 ) in the EC – DCb arm . Grade 3/4 toxicity was similar in both arms . The addition of carboplatin to conventional chemotherapy with EC – D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent . These findings should be taken into consideration when developing new agents for this disease Abstract Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response ( pCR ) rates . We evaluated the efficacy and safety of carboplatin and weekly paclitaxel ( wPTX ) followed by cyclophosphamide , epirubicin , and 5-fluorouracil ( CEF ) as neoadjuvant chemotherapy for HER2-negative breast cancer . Patients with stage II/IIIA HER2-negative breast cancer were r and omly assigned to preoperatively receive CP-CEF ( four 3-week cycles of carboplatin [ area under the curve 5 mg/mL/min , day 1 ] and wPTX [ 80 mg/m2 , day 1 , 8 , 15 ] followed by four 3-week cycles of CEF [ 500/100/500 mg/m2 ] or P-CEF ( four cycles of wPTX followed by four cycles of CEF ) . The primary objective was pCR rate .  Of 181 eligible patients , 89 were r and omly assigned to the  CP-CEF  and 92 to the P-CEF . Two patients in each arm refused to receive neoadjuvant chemotherapy . Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety . The pCR rate in the CP-CEF was significantly higher than that in the P-CEF ( 31.8 vs. 17.6 % , one-sided P = 0.01 ) . Among patients with triple-negative breast cancer , the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [ 61.2 ( 23/37 ) vs. 26.3 % ( 10/38 ) , P = 0.003 ] . Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF ( 65.9 vs. 38.5 % ) . Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity Purpose Docetaxel and cyclophosphamide ( TC ) was superior to doxorubicin and cyclophosphamide ( AC ) in a trial in early breast cancer . However , activity of TC relative to AC regimens with a taxane ( TaxAC ) is unknown . Methods In a series of three adjuvant trials , women were r and omly assigned to TC for six cycles ( TC6 ) or to a  st and ard TaxAC regimen .  US Oncology Research ( USOR ) 06 - 090 compared TC6 with docetaxel , doxorubicin , and cyclophosphamide ( TAC6 ) . National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-46-I/USOR 07132 compared TC6 , TAC6 , or TC6 plus bevacizumab . NSABP B-49 compared TC6 with several st and ard AC and taxane combination regimens . Before any analysis of individual trials , a joint efficacy analysis of TC versus the TaxAC regimens was planned , with invasive disease-free survival ( IDFS ) as the primary end point . Patients who received TC6 plus bevacizumab  on NSABP B-46-I/USOR 07132 were not included . A hazard ratio ( HR ) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6 . The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed ( 50 % of 668 events required for definitive analysis ) . Results A total of 2,125 patients were r and omly assigned to receive TC6 regimens and 2,117 patients were r and 
    Output:
    