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 Abstract The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer ( TNBC ) , and to explore biomarkers based on DNA and protein expression profiles as predictors of response . Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days , and eribulin 1.4 mg/m2 day 1 and day 8 every 21 days for four cycles . The primary endpoint of the study was pathologic complete response ( pCR ) , with secondary endpoints including clinical response and safety of the combination . Exploratory studies assessed DNA-based biomarkers [ homologous recombination deficiency ( HRD ) score , and HR deficiency status ( HRD score + BRCA1/BRCA2 mutation status ) ] , protein-based biomarkers ( Ki67 , TP53 , and rogen receptor , Cyclin E , CDK2 , Cyclin D , CDK4 , Pin1 and Smad3 ) , and clinical pretreatment factors as predictors of pCR . 13/30 ( 43.3 % ) patients enrolled in the study achieved pCR . 24 ( 80.0 % ) had a clinical complete or partial response . The combination was safe with mostly grade 1 and 2 toxicities . HRD score ( P = 0.0024 ) and HR deficiency status ( P = 0.0012 ) significantly predicted pCR . Pretreatment cytoplasmic CDK2 was also associated with pCR ( P = 0.021 ) . Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D ( P = 0.020 ) , nuclear CDK4 ( P = 0.0030 ) , and nuclear Smad3 ( P = 0.015 ) were detected . The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC . HRD score , HR deficiency status , and cytoplasmic CDK2 predicted pCR in this patient population Purpose : Recent studies demonstrate that addition of neoadjuvant ( NA ) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response ( pCR ) in triple-negative breast cancer ( TNBC ) . Effectiveness of anthracycline-free platinum combinations in TNBC is not well known . Here , we report efficacy of NA carboplatin + docetaxel ( CbD ) in TNBC . Experimental Design : The study population includes 190 patients with stage I – III TNBC treated uniformly on two independent prospect i ve cohorts . All patients were prescribed NA chemotherapy regimen of carboplatin ( AUC 6 ) + docetaxel ( 75 mg/m2 ) given every 21 days × 6 cycles . pCR ( no evidence of invasive tumor in the breast and axilla ) and residual cancer burden ( RCB ) were evaluated . Results : Among 190 patients , median tumor size was 35 mm , 52 % were lymph node positive , and 16 % had germline BRCA1/2 mutation .  The overall pCR and RCB 0 + 1 rates were 55 % and 68 % , respectively . pCRs in patients with BRCA-associated and wild-type TNBC were 59 % and 56 % , respectively ( P = 0.83 ) . On multivariable analysis , stage III disease was the only factor associated with a lower likelihood of achieving a pCR . Twenty-one percent and 7 % of patients , respectively , experienced at least one grade 3 or 4 adverse event . Conclusions : The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC . These results are comparable with pCR achieved with the addition of carboplatin to anthracycline – taxane chemotherapy . Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in r and omized studies . Clin Cancer Res ; 23(3 ) ; 649–57 . © 2016 AACR Purpose As triple-negative breast cancers are associated with earlier recurrences and poorer survival , optimal treatment of early-stage breast cancer is essential . Several retrospective studies in triple-negative breast cancer have reported conflicting results in overall survival in patients receiving neoadjuvant or adjuvant systemic therapy . This study aims to analyze outcomes of adjuvant versus neoadjuvant in patients with early-stage triple-negative breast cancer with and without BRCA germline mutations . Methods Patients with stage I or II triple-negative breast cancer who had BRCA testing were identified from a prospect i ve cohort study of 4027 patients .  Clinical , demographic , genetic test results , chemotherapy , recurrence , and survival data were analyzed . Overall survival and disease-free survival were estimated using the Kaplan – Meier method . Results 319 patients with stage I and II triple-negative breast cancer who met eligibility criteria were included in the analysis . 187 received adjuvant chemotherapy ( 58.6 % ) and 132 received neoadjuvant chemotherapy ( 41.4 % ) . 135 were BRCA positive ( 42.3 % ) and 184 were BRCA negative ( 57.7 % ) . There was no significant association between overall survival or disease-free survival and treatment with neoadjuvant versus adjuvant in the overall cohort . Furthermore , there were no significant differences between patient subgroups ( neoadjuvant BRCA positive , neoadjuvant BRCA negative , adjuvant BRCA positive , and adjuvant BRCA negative ) with respect to either overall survival or disease-free survival .  Conclusions Neoadjuvant versus adjuvant with st and ard anthracycline- and taxane-containing regimens results in similar disease-free survival and overall survival among patients with stage I and II triple-negative breast cancer regardless of BRCA status . Further studies are needed to evaluate whether similar results are observed with newer agents 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 
    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 Abstract The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer ( TNBC ) , and to explore biomarkers based on DNA and protein expression profiles as predictors of response . Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days , and eribulin 1.4 mg/m2 day 1 and day 8 every 21 days for four cycles . The primary endpoint of the study was pathologic complete response ( pCR ) , with secondary endpoints including clinical response and safety of the combination . Exploratory studies assessed DNA-based biomarkers [ homologous recombination deficiency ( HRD ) score , and HR deficiency status ( HRD score + BRCA1/BRCA2 mutation status ) ] , protein-based biomarkers ( Ki67 , TP53 , and rogen receptor , Cyclin E , CDK2 , Cyclin D , CDK4 , Pin1 and Smad3 ) , and clinical pretreatment factors as predictors of pCR . 13/30 ( 43.3 % ) patients enrolled in the study achieved pCR . 24 ( 80.0 % ) had a clinical complete or partial response . The combination was safe with mostly grade 1 and 2 toxicities . HRD score ( P = 0.0024 ) and HR deficiency status ( P = 0.0012 ) significantly predicted pCR . Pretreatment cytoplasmic CDK2 was also associated with pCR ( P = 0.021 ) . Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D ( P = 0.020 ) , nuclear CDK4 ( P = 0.0030 ) , and nuclear Smad3 ( P = 0.015 ) were detected . The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC . HRD score , HR deficiency status , and cytoplasmic CDK2 predicted pCR in this patient population Purpose : Recent studies demonstrate that addition of neoadjuvant ( NA ) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response ( pCR ) in triple-negative breast cancer ( TNBC ) . Effectiveness of anthracycline-free platinum combinations in TNBC is not well known . Here , we report efficacy of NA carboplatin + docetaxel ( CbD ) in TNBC . Experimental Design : The study population includes 190 patients with stage I – III TNBC treated uniformly on two independent prospect i ve cohorts . All patients were prescribed NA chemotherapy regimen of carboplatin ( AUC 6 ) + docetaxel ( 75 mg/m2 ) given every 21 days × 6 cycles . pCR ( no evidence of invasive tumor in the breast and axilla ) and residual cancer burden ( RCB ) were evaluated . Results : Among 190 patients , median tumor size was 35 mm , 52 % were lymph node positive , and 16 % had germline BRCA1/2 mutation .  The overall pCR and RCB 0 + 1 rates were 55 % and 68 % , respectively . pCRs in patients with BRCA-associated and wild-type TNBC were 59 % and 56 % , respectively ( P = 0.83 ) . On multivariable analysis , stage III disease was the only factor associated with a lower likelihood of achieving a pCR . Twenty-one percent and 7 % of patients , respectively , experienced at least one grade 3 or 4 adverse event . Conclusions : The CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC . These results are comparable with pCR achieved with the addition of carboplatin to anthracycline – taxane chemotherapy . Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in r and omized studies . Clin Cancer Res ; 23(3 ) ; 649–57 . © 2016 AACR Purpose As triple-negative breast cancers are associated with earlier recurrences and poorer survival , optimal treatment of early-stage breast cancer is essential . Several retrospective studies in triple-negative breast cancer have reported conflicting results in overall survival in patients receiving neoadjuvant or adjuvant systemic therapy . This study aims to analyze outcomes of adjuvant versus neoadjuvant in patients with early-stage triple-negative breast cancer with and without BRCA germline mutations . Methods Patients with stage I or II triple-negative breast cancer who had BRCA testing were identified from a prospect i ve cohort study of 4027 patients .  Clinical , demographic , genetic test results , chemotherapy , recurrence , and survival data were analyzed . Overall survival and disease-free survival were estimated using the Kaplan – Meier method . Results 319 patients with stage I and II triple-negative breast cancer who met eligibility criteria were included in the analysis . 187 received adjuvant chemotherapy ( 58.6 % ) and 132 received neoadjuvant chemotherapy ( 41.4 % ) . 135 were BRCA positive ( 42.3 % ) and 184 were BRCA negative ( 57.7 % ) . There was no significant association between overall survival or disease-free survival and treatment with neoadjuvant versus adjuvant in the overall cohort . Furthermore , there were no significant differences between patient subgroups ( neoadjuvant BRCA positive , neoadjuvant BRCA negative , adjuvant BRCA positive , and adjuvant BRCA negative ) with respect to either overall survival or disease-free survival .  Conclusions Neoadjuvant versus adjuvant with st and ard anthracycline- and taxane-containing regimens results in similar disease-free survival and overall survival among patients with stage I and II triple-negative breast cancer regardless of BRCA status . Further studies are needed to evaluate whether similar results are observed with newer agents 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 
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