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 Purpose : Gene expression analysis identifies several breast cancer subtypes . We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes . Experimental Design : We used immunohistochemical profiles [ human epidermal growth factor receptor 2–positive (HER2+)/hormone receptor – negative for HER2+/estrogen receptor – negative ( ER− ) , hormone receptor and HER2− for basal-like , hormone receptor – positive for luminal ] to subtype a prospect ively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based ( doxorubicin plus cyclophosphamide , AC ) chemotherapy .  We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease – free survival and overall survival . Results : Of the 107 patients tested , 34 ( 32 % ) were basal-like , 11 ( 10 % ) were HER2+/ER− , and 62 ( 58 % ) were luminal . After neoadjuvant AC , 75 % received subsequent chemotherapy and all received endocrine therapy if hormone receptor – positive . The chemotherapy regimen and pretreatment stage did not differ by subtype . Clinical response to AC  was higher among the HER2+/ER− ( 70 % ) and basal-like ( 85 % ) than the luminal subtypes ( 47 % ; P < 0.0001 ) . Pathologic complete response occurred in 36 % of HER2+/ER− , 27 % of basal-like , and 7 % of luminal subtypes ( P = 0.01 ) . Despite initial chemosensitivity , patients with the basal-like and HER2+/ER− subtypes had worse distant disease – free survival ( P = 0.04 ) and overall survival ( P = 0.02 ) than those with the luminal subtypes . Regardless of subtype , only 2 of 17 patients with pathologic complete response relapsed . The worse outcome among basal-like and HER+/ER− subtypes was due to higher relapse among those with residual disease ( P = 0.003 ) . Conclusions : Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers . Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype . The poorer prognosis of basal-like and HER2+/ER− breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved Importance The GeparSixto trial provided evidence that the addition of neoadjuvant carboplatin to a regimen consisting of anthracycline , taxane , and bevacizumab increases pathological complete response ( pCR ) rates in patients with triple-negative breast cancer ( TNBC ) . Whether BRCA1 and BRCA2 germline mutation status affects treatment outcome remains elusive . Objective To determine whether BRCA1 and BRCA2 germline mutation status affects therapy response in patients with TNBC . Design , Setting , and Participants This secondary analysis of a r and omized clinical trial used archived DNA sample s and cancer family history of 315 patients with TNBC enrolled between August 1 , 2011 , and December 31 , 2012 , in the GeparSixto trial . In all , 291 participants ( 92.4 % ) were included in this multicenter prospect i ve investigation . DNA sample s were analyzed for germline mutations in BRCA1 , BRCA2 , and 16 other cancer predisposition genes . The pCR rates between the carboplatin and noncarboplatin arms were compared . Genetic analyses were performed at the Center for Familial Breast and Ovarian Cancer in Cologne , Germany ; data analysis , November 1 through December 31 , 2015 . Main Outcomes and Measures Proportion of patients who achieved pCR and disease-free survival after neoadjuvant treatment according to BRCA1 and BRCA2 germline mutation status . For pCR rates , the ypT0/is ypN0 definition was used as a primary end point . Results Of the 291 patients with TNBC , all were women ; the mean ( SD ) age was 48 ( 11 ) years . The pCR rate in the carboplatin group was 56.8 % ( 83 of 146 ) and 41.4 % ( 60 of 145 ) in the noncarboplatin group ( odds ratio [ OR ] , 1.87 ; 95 % CI , 1.17 - 2.97 ; P = .009 ) . Pathogenic BRCA1 and BRCA2 germline mutations were present in 50 of the 291 patients ( 17.2 % ) . In the noncarboplatin arm , the pCR rate was 66.7 % ( 16 of 24 ) for patients with BRCA1 and BRCA2 mutations and 36.4 % ( 44 of 121 ) for patients without ( OR , 3.50 ; 95 % CI , 1.39 - 8.84 ; P = .008 ) . The high pCR rate observed in BRCA1 and BRCA2 mutation carriers ( 16 of 24 [ 66.7 % ] ) was not increased further by adding carboplatin ( 17 of 26 [ 65.4 % ] ) . In contrast , carboplatin increased response rates in patients without BRCA1 and BRCA2 mutations : 66 of the 120 patients ( 55 % ) without BRCA1 and BRCA2 mutations achieved pCR in the carboplatin arm vs 44 of the 121 patients ( 36.4 % ) in the noncarboplatin arm ( OR , 2.14 ; 95 % CI , 1.28 - 3.58 ; P = .004 ) . Patients without pathogenic BRCA1 and BRCA2 alterations showed elevated disease-free survival rates when carboplatin was added ( without carboplatin , 73.5 % ; 95 % CI , 64.1%-80.8 % vs with carboplatin , 85.3 % ; 95 % CI , 77.0%-90.8 % ; hazard ratio , 0.53 ; 95 % CI , 0.29 - 0.96 ; P = .04 ) . Conclusions and Relevance Under the nonst and ard GeparSixto polychemotherapy regimen , patients without BRCA1 and BRCA2 germline mutations benefited from the addition of carboplatin and those with BRCA1 and BRCA2 mutations showed superior response rates without additive effects observed for carboplatin . Trial Registration clinical trials.gov Identifier : The aim of this study is to estimate the frequency of pathologic complete response ( pCR ) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation . One hundred and seven women with breast cancer and a BRCA1 mutation , who were diagnosed with stage I to III breast cancer between December 2006 and June 2014 , were treated with cisplatin 75 mg/m2 every 3 weeks for four cycles , followed by mastectomy and conventional chemotherapy . Information was collected on clinical stage , grade , hormone receptor status , and Her2neu status prior to treatment . pCR was determined by review of surgical specimens . One hundred and seven patients were enrolled in the study , including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer .  A pCR was observed in 65 of the 107 patients ( 61 % ) . Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer NCCN guidelines recommend genetic testing for all triple-negative breast cancer ( TNBC ) patients aged ≤60 years . However , due to the lack of prospect i ve information in unselected patients , these guidelines are not uniformly adopted by clinicians and insurance carriers . The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population . Stage I – IV TNBC patients were enrolled on a prospect i ve registry at academic and community practice s. All patients underwent BRCA1/2 testing . Signific 
    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 Purpose : Gene expression analysis identifies several breast cancer subtypes . We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes . Experimental Design : We used immunohistochemical profiles [ human epidermal growth factor receptor 2–positive (HER2+)/hormone receptor – negative for HER2+/estrogen receptor – negative ( ER− ) , hormone receptor and HER2− for basal-like , hormone receptor – positive for luminal ] to subtype a prospect ively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based ( doxorubicin plus cyclophosphamide , AC ) chemotherapy .  We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease – free survival and overall survival . Results : Of the 107 patients tested , 34 ( 32 % ) were basal-like , 11 ( 10 % ) were HER2+/ER− , and 62 ( 58 % ) were luminal . After neoadjuvant AC , 75 % received subsequent chemotherapy and all received endocrine therapy if hormone receptor – positive . The chemotherapy regimen and pretreatment stage did not differ by subtype . Clinical response to AC  was higher among the HER2+/ER− ( 70 % ) and basal-like ( 85 % ) than the luminal subtypes ( 47 % ; P < 0.0001 ) . Pathologic complete response occurred in 36 % of HER2+/ER− , 27 % of basal-like , and 7 % of luminal subtypes ( P = 0.01 ) . Despite initial chemosensitivity , patients with the basal-like and HER2+/ER− subtypes had worse distant disease – free survival ( P = 0.04 ) and overall survival ( P = 0.02 ) than those with the luminal subtypes . Regardless of subtype , only 2 of 17 patients with pathologic complete response relapsed . The worse outcome among basal-like and HER+/ER− subtypes was due to higher relapse among those with residual disease ( P = 0.003 ) . Conclusions : Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers . Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype . The poorer prognosis of basal-like and HER2+/ER− breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved Importance The GeparSixto trial provided evidence that the addition of neoadjuvant carboplatin to a regimen consisting of anthracycline , taxane , and bevacizumab increases pathological complete response ( pCR ) rates in patients with triple-negative breast cancer ( TNBC ) . Whether BRCA1 and BRCA2 germline mutation status affects treatment outcome remains elusive . Objective To determine whether BRCA1 and BRCA2 germline mutation status affects therapy response in patients with TNBC . Design , Setting , and Participants This secondary analysis of a r and omized clinical trial used archived DNA sample s and cancer family history of 315 patients with TNBC enrolled between August 1 , 2011 , and December 31 , 2012 , in the GeparSixto trial . In all , 291 participants ( 92.4 % ) were included in this multicenter prospect i ve investigation . DNA sample s were analyzed for germline mutations in BRCA1 , BRCA2 , and 16 other cancer predisposition genes . The pCR rates between the carboplatin and noncarboplatin arms were compared . Genetic analyses were performed at the Center for Familial Breast and Ovarian Cancer in Cologne , Germany ; data analysis , November 1 through December 31 , 2015 . Main Outcomes and Measures Proportion of patients who achieved pCR and disease-free survival after neoadjuvant treatment according to BRCA1 and BRCA2 germline mutation status . For pCR rates , the ypT0/is ypN0 definition was used as a primary end point . Results Of the 291 patients with TNBC , all were women ; the mean ( SD ) age was 48 ( 11 ) years . The pCR rate in the carboplatin group was 56.8 % ( 83 of 146 ) and 41.4 % ( 60 of 145 ) in the noncarboplatin group ( odds ratio [ OR ] , 1.87 ; 95 % CI , 1.17 - 2.97 ; P = .009 ) . Pathogenic BRCA1 and BRCA2 germline mutations were present in 50 of the 291 patients ( 17.2 % ) . In the noncarboplatin arm , the pCR rate was 66.7 % ( 16 of 24 ) for patients with BRCA1 and BRCA2 mutations and 36.4 % ( 44 of 121 ) for patients without ( OR , 3.50 ; 95 % CI , 1.39 - 8.84 ; P = .008 ) . The high pCR rate observed in BRCA1 and BRCA2 mutation carriers ( 16 of 24 [ 66.7 % ] ) was not increased further by adding carboplatin ( 17 of 26 [ 65.4 % ] ) . In contrast , carboplatin increased response rates in patients without BRCA1 and BRCA2 mutations : 66 of the 120 patients ( 55 % ) without BRCA1 and BRCA2 mutations achieved pCR in the carboplatin arm vs 44 of the 121 patients ( 36.4 % ) in the noncarboplatin arm ( OR , 2.14 ; 95 % CI , 1.28 - 3.58 ; P = .004 ) . Patients without pathogenic BRCA1 and BRCA2 alterations showed elevated disease-free survival rates when carboplatin was added ( without carboplatin , 73.5 % ; 95 % CI , 64.1%-80.8 % vs with carboplatin , 85.3 % ; 95 % CI , 77.0%-90.8 % ; hazard ratio , 0.53 ; 95 % CI , 0.29 - 0.96 ; P = .04 ) . Conclusions and Relevance Under the nonst and ard GeparSixto polychemotherapy regimen , patients without BRCA1 and BRCA2 germline mutations benefited from the addition of carboplatin and those with BRCA1 and BRCA2 mutations showed superior response rates without additive effects observed for carboplatin . Trial Registration clinical trials.gov Identifier : The aim of this study is to estimate the frequency of pathologic complete response ( pCR ) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation . One hundred and seven women with breast cancer and a BRCA1 mutation , who were diagnosed with stage I to III breast cancer between December 2006 and June 2014 , were treated with cisplatin 75 mg/m2 every 3 weeks for four cycles , followed by mastectomy and conventional chemotherapy . Information was collected on clinical stage , grade , hormone receptor status , and Her2neu status prior to treatment . pCR was determined by review of surgical specimens . One hundred and seven patients were enrolled in the study , including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer .  A pCR was observed in 65 of the 107 patients ( 61 % ) . Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer NCCN guidelines recommend genetic testing for all triple-negative breast cancer ( TNBC ) patients aged ≤60 years . However , due to the lack of prospect i ve information in unselected patients , these guidelines are not uniformly adopted by clinicians and insurance carriers . The aim of this study was to determine the prevalence of BRCA mutations and evaluate the utility of NCCN guidelines in unselected TNBC population . Stage I – IV TNBC patients were enrolled on a prospect i ve registry at academic and community practice s. All patients underwent BRCA1/2 testing . Signific 
    Output:
    