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: PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant ( HERA ) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy . PATIENTS AND METHODS The HERA trial is a three-group , r and omized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 ( HER2 ) -positive early breast cancer . Eligible patients had normal left ventricular ejection fraction ( LVEF ; > or= 55 % ) after completion of (neo)adjuvant chemotherapy with or without radiotherapy .  Cardiac function was monitored throughout the trial . This analysis considers patients r and omly assigned to 1 year of trastuzumab treatment or observation . RESULTS There were 1,698 patients r and omly assigned to observation and 1,703 r and omly assigned to 1 year of trastuzumab treatment ; 94.1 % of patients had been treated with anthracyclines . The incidence of discontinuation of trastuzumab because of cardiac disorders was low ( 5.1 % ) . At a median follow-up of 3.6 years , the incidence of cardiac end points remained low , though it was higher in the trastuzumab group than in the observation group ( severe CHF , 0.8 % v 0.0 % ; confirmed significant LVEF decreases , 3.6 % v 0.6 % ) In the trastuzumab group , 59 of 73 patients with a cardiac end point reached acute recovery ; of these 59 patients , 52 were considered by the cardiac advisory board ( CAB ) to have a favorable outcome from the cardiac end point . CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up . The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year , but it remains relatively constant thereafter PURPOSE To assess patient and tumor characteristics associated with a complete pathologic response ( pCR ) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Three hundred seventy-two LABC patients received treatment in two prospect i ve neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy .  Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy .  Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics . Median follow-up was 58 months ( range , 8 to 99 months ) . RESULTS The initial nodal status , age , and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR ( P>.05 ) . Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative ( P<.01 ) , and anaplastic ( P = .01 ) but of smaller size ( P<.01 ) than those of patients with less than a pCR . Upon multivariate analysis , the effects of ER status and nuclear grade were independent of initial tumor size . Sixteen percent of the patients in this study ( n = 60 ) had a pathologic complete primary tumor response . Twelve percent of patients ( n = 43 ) had no microscopic evidence of invasive cancer in their breast and axillary specimens . A pathologic complete primary tumor response was predictive of a complete axillary lymph node response ( P<.01 ) . The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR ( 89 % and 87 % , respectively ) than in the group who had less than a pCR ( 64 % and 58 % , respectively ; P<.01 ) . CONCLUSION Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery . Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate . However , a pCR does not entirely eliminate recurrence . Further efforts should focus on elucidating the molecular mechanisms associated with this response OBJECTIVE To assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab ( TH ) in Chinese women with Her-2 overexpressing operable breast cancer . METHODS This is a single center open-label phase II clinical trial . The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery . The primary endpoint was pathologic complete response rate ( pCR rate ) and the secondary endpoint was overall response rate ( OR rate ) . Patients were also stratified according to hormone receptor status , and pCR rate and OR rate were compared between subgroups . Adverse events were grade d according to CTCAE v3.0 . RESULTS There were 40 eligible patients entering this study with median age of 49 years . All patients completed 4 cycles of neoadjuvant treatment . pCR rate was 52.5 % and OR rate was 87.5 % . The differences of pCR and OR rates between subgroups were of no statistical significance . No cardiac toxicity event severer than grade 2 was recorded . CONCLUSION 3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the r and omized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients . From May 2004 till October 2007 , 340 patients with stage II and III breast adenocarcinoma , ineligible for breast conserving surgery , received eight sequential three weekly cycles of EC-D [ epirubicin ( 75 mg/m2)–cyclophosphamide ( 750 mg/m2 ) for four cycles followed by docetaxel ( 100 mg/m2 ) for four cycles ] . HER2-negative patients ( N = 220 ) were r and omized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment , while HER2-positive patients confirmed by FISH ( N = 120 ) were r and omized to trastuzumab concomitant to docetaxel ( 8 mg/kg then 6 mg/kg IV every 3 weeks ) or no additional preoperative treatment . In the HER2 negative group , pCR ( grade 1 and 2 of Chevallier ’s classification ) was observed in 11.5 and 13 % of patients treated without and with neoadjuvant Celecoxib , respectively . In the HER2 positive group , pCR rate reached 26 % in those who received neoadjuvant trastuzumab versus 19 % in the others . There was no unexpected toxicity , no cardiac toxicity , and no toxic death . Triple negative breast cancers experience the highest pCR rate of 30 % . Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor . In HER2-positive tumor patients , trastuzumab added to ECD leads to increased pCR rates . It was the only combination to deserve further study according to the two-stage Fleming ’s design used in this trial National Surgical Adjuvant Breast and Bowel Project ( NSABP ) Protocol B-18 was initiated in 1988 to determine whether four cycles of doxorubicin/cyclophosphamide given preoperatively improve survival and disease-free survival ( DFS ) when compared with the same chemotherapy given postoperatively . Secondary aims included the evaluation of preoperative chemotherapy in downstaging the primary breast tumor and involved axillary lymph nodes , the comparison of lumpectomy rates and rates of ipsilateral breast tumor recurrence ( IBTR ) in the two treatment groups , and the assessment of the correlation between primary tumor response and outcome . Initially published findings were based on a follow-up of 5 years ; this report up date s results through 9 years of follow-up . There continue to be no statistically significant overall differences in survival or DFS between the two treatment groups . Survival at 9 years is 70 % in the postoperative group and 69 % in the preoperative group ( P = .80 ) . DFS is 53 % in postoperative patients and 55 % in preoperative patients ( P = .50 ) . A statistically significant correlation persists between primary tumor response and outcome , and this correlation has become statistically stronger with longer follow-up . Patients assigned to preoperative chemotherapy  received notably more lumpectomies than postoperative patients , especially among patients with tumors greater than 5 cm at study entry . Although the rate of IBTR was slightly higher in the preoperative group ( 10.7 % versus 7.6 % ) , this difference was not statistically significant . Marginally statistically significant treatment-by-age interactions appear to be emerging for survival and DFS , suggesting that younger patients may benefit from preoperative therapy , whereas the reverse may be true for older patients PURPOSE To determine , in women with primary operable breast cancer , if preoperative doxorubicin ( Adriamycin ) and cyclophosphamide ( Cytoxan ; AC ) therapy yields a better outcome than postoperative AC therapy , if a relationship exists between outcome and tumor response to preoperative chemotherapy , and if such therapy results in the performance of more lumpectomies . PATIENTS AND METHODS Women ( 1,523 ) enrolled onto National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-18 were r and omly assigned to preoperative or postoperative AC therapy . Clinical tumor response to preoperative therapy was grade d as complete ( cCR ) , partial ( cPR ) , or no response ( cNR ) . Tumors with a cCR were further categorized as either pathologic complete response ( pCR ) or invasive cells ( pINV ) . Disease-free survival ( DFS ) , distant disease-free survival ( DDFS ) , and survival were estimated through 5 years and compared between treatment groups . In the preoperative arm , proportional-hazards models were used to investigate the relationship between outcome and tumor response . RESULTS There was no significant difference in DFS , DDFS , or survival ( P = .99 , .70 , and .83 , respectively ) among patients in either group . More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy ( 67.8 % v 59.8 % , respectively ) . Rates of ipsilateral breast tumor recurrence ( IBTR ) after lumpectomy were similar in both groups ( 7.9 % and 5.8 % , respectively ; P = .23 ) . Outcome was better in women whose tumors showed a pCR than in those with a pINV , cPR , or cNR ( relapse-free survival [ RFS ] rates , 85.7 % , 76.9 % , 68.1 % , and 63.9 % , respectively ; P < .0001 ) , even when baseline prognostic variables were controlled . When prognostic models were compared for each treatment group , the preoperative model , which included breast tumor response as a variable , discriminated outcome among patients to about the same degree as the postoperative model . CONCLUSION Preoperative chemotherapy is as effective as postoperative chemotherapy , permits more lumpectomies , is appropriate for the treatment of certain patients with stages I and II disease , and can be used to study breast cancer biology . Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases ; however , knowledge of such a response provided little prognostic information beyond that which result ed from postoperative therapy 10515 Background : A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin ( T/C ) with or without trastuzumab ( H ) in women with stage III breast cancer . METHODS Forty-eight of 75 planned primary breast cancer patients ( T3 or T4 , any N , M0 ) , age between 18 and 80 have been enrolled . Four cycles of T ( 75 mg/m2 ) + C ( AUC 6 ) were given every 3 weeks preoperatively . Patients with HER-2 amplified tumors ( FISH + ) were r and omized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively . Tumors were assessed clinical ly at baseline and after neoadjuvant therapy . Cardiac assessment consisted of medical history , EKG and LVEF ( by echocardiogram or MUGA ) at baseline and at the end of neoadjuvant chemotherapy . RESULTS Available data from 45 of 48 enrolled patients showed 49 % ( 22 cases ) with complete clinical response , with 54.5 % being HER-2 ( + ) ( 12 cases ) . Stable disease was seen in one patient who was HER-2 ( - ) ( 2.2 % ) . Of 37 with complete pathology verification , 11 ( 29.7 % ) showed pathologic complete response ( pCR ) of the primary tumor with 5 cases being HER-2 ( + ) . Of the 22 HER-2 ( + ) cases that completed neoadjuvant treatment , 11 received T/C/H and 11 received T/C. pCR was noted in 36.4 % of the T/C/H group and 9 % of the T/C  group . LVEF data is available from 43 patients during the neoadjuvant phase , showing 18.6 
    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: PURPOSE We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant ( HERA ) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy . PATIENTS AND METHODS The HERA trial is a three-group , r and omized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 ( HER2 ) -positive early breast cancer . Eligible patients had normal left ventricular ejection fraction ( LVEF ; > or= 55 % ) after completion of (neo)adjuvant chemotherapy with or without radiotherapy .  Cardiac function was monitored throughout the trial . This analysis considers patients r and omly assigned to 1 year of trastuzumab treatment or observation . RESULTS There were 1,698 patients r and omly assigned to observation and 1,703 r and omly assigned to 1 year of trastuzumab treatment ; 94.1 % of patients had been treated with anthracyclines . The incidence of discontinuation of trastuzumab because of cardiac disorders was low ( 5.1 % ) . At a median follow-up of 3.6 years , the incidence of cardiac end points remained low , though it was higher in the trastuzumab group than in the observation group ( severe CHF , 0.8 % v 0.0 % ; confirmed significant LVEF decreases , 3.6 % v 0.6 % ) In the trastuzumab group , 59 of 73 patients with a cardiac end point reached acute recovery ; of these 59 patients , 52 were considered by the cardiac advisory board ( CAB ) to have a favorable outcome from the cardiac end point . CONCLUSION The incidence of cardiac end points remains low even after longer-term follow-up . The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year , but it remains relatively constant thereafter PURPOSE To assess patient and tumor characteristics associated with a complete pathologic response ( pCR ) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer ( LABC ) . PATIENTS AND METHODS Three hundred seventy-two LABC patients received treatment in two prospect i ve neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy .  Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy .  Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics . Median follow-up was 58 months ( range , 8 to 99 months ) . RESULTS The initial nodal status , age , and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR ( P>.05 ) . Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative ( P<.01 ) , and anaplastic ( P = .01 ) but of smaller size ( P<.01 ) than those of patients with less than a pCR . Upon multivariate analysis , the effects of ER status and nuclear grade were independent of initial tumor size . Sixteen percent of the patients in this study ( n = 60 ) had a pathologic complete primary tumor response . Twelve percent of patients ( n = 43 ) had no microscopic evidence of invasive cancer in their breast and axillary specimens . A pathologic complete primary tumor response was predictive of a complete axillary lymph node response ( P<.01 ) . The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR ( 89 % and 87 % , respectively ) than in the group who had less than a pCR ( 64 % and 58 % , respectively ; P<.01 ) . CONCLUSION Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery . Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate . However , a pCR does not entirely eliminate recurrence . Further efforts should focus on elucidating the molecular mechanisms associated with this response OBJECTIVE To assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab ( TH ) in Chinese women with Her-2 overexpressing operable breast cancer . METHODS This is a single center open-label phase II clinical trial . The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery . The primary endpoint was pathologic complete response rate ( pCR rate ) and the secondary endpoint was overall response rate ( OR rate ) . Patients were also stratified according to hormone receptor status , and pCR rate and OR rate were compared between subgroups . Adverse events were grade d according to CTCAE v3.0 . RESULTS There were 40 eligible patients entering this study with median age of 49 years . All patients completed 4 cycles of neoadjuvant treatment . pCR rate was 52.5 % and OR rate was 87.5 % . The differences of pCR and OR rates between subgroups were of no statistical significance . No cardiac toxicity event severer than grade 2 was recorded . CONCLUSION 3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety To assess anti-tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the r and omized addition of celecoxib in HER2 negative patients or trastuzumab in HER2 positive patients . From May 2004 till October 2007 , 340 patients with stage II and III breast adenocarcinoma , ineligible for breast conserving surgery , received eight sequential three weekly cycles of EC-D [ epirubicin ( 75 mg/m2)–cyclophosphamide ( 750 mg/m2 ) for four cycles followed by docetaxel ( 100 mg/m2 ) for four cycles ] . HER2-negative patients ( N = 220 ) were r and omized to receive concomitantly with docetaxel celecoxib 800 mg/day during cycles 5–8 or no additional treatment , while HER2-positive patients confirmed by FISH ( N = 120 ) were r and omized to trastuzumab concomitant to docetaxel ( 8 mg/kg then 6 mg/kg IV every 3 weeks ) or no additional preoperative treatment . In the HER2 negative group , pCR ( grade 1 and 2 of Chevallier ’s classification ) was observed in 11.5 and 13 % of patients treated without and with neoadjuvant Celecoxib , respectively . In the HER2 positive group , pCR rate reached 26 % in those who received neoadjuvant trastuzumab versus 19 % in the others . There was no unexpected toxicity , no cardiac toxicity , and no toxic death . Triple negative breast cancers experience the highest pCR rate of 30 % . Celecoxib is not likely to improve pCR rates in addition to EC-D in patients with HER2-negative tumor . In HER2-positive tumor patients , trastuzumab added to ECD leads to increased pCR rates . It was the only combination to deserve further study according to the two-stage Fleming ’s design used in this trial National Surgical Adjuvant Breast and Bowel Project ( NSABP ) Protocol B-18 was initiated in 1988 to determine whether four cycles of doxorubicin/cyclophosphamide given preoperatively improve survival and disease-free survival ( DFS ) when compared with the same chemotherapy given postoperatively . Secondary aims included the evaluation of preoperative chemotherapy in downstaging the primary breast tumor and involved axillary lymph nodes , the comparison of lumpectomy rates and rates of ipsilateral breast tumor recurrence ( IBTR ) in the two treatment groups , and the assessment of the correlation between primary tumor response and outcome . Initially published findings were based on a follow-up of 5 years ; this report up date s results through 9 years of follow-up . There continue to be no statistically significant overall differences in survival or DFS between the two treatment groups . Survival at 9 years is 70 % in the postoperative group and 69 % in the preoperative group ( P = .80 ) . DFS is 53 % in postoperative patients and 55 % in preoperative patients ( P = .50 ) . A statistically significant correlation persists between primary tumor response and outcome , and this correlation has become statistically stronger with longer follow-up . Patients assigned to preoperative chemotherapy  received notably more lumpectomies than postoperative patients , especially among patients with tumors greater than 5 cm at study entry . Although the rate of IBTR was slightly higher in the preoperative group ( 10.7 % versus 7.6 % ) , this difference was not statistically significant . Marginally statistically significant treatment-by-age interactions appear to be emerging for survival and DFS , suggesting that younger patients may benefit from preoperative therapy , whereas the reverse may be true for older patients PURPOSE To determine , in women with primary operable breast cancer , if preoperative doxorubicin ( Adriamycin ) and cyclophosphamide ( Cytoxan ; AC ) therapy yields a better outcome than postoperative AC therapy , if a relationship exists between outcome and tumor response to preoperative chemotherapy , and if such therapy results in the performance of more lumpectomies . PATIENTS AND METHODS Women ( 1,523 ) enrolled onto National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-18 were r and omly assigned to preoperative or postoperative AC therapy . Clinical tumor response to preoperative therapy was grade d as complete ( cCR ) , partial ( cPR ) , or no response ( cNR ) . Tumors with a cCR were further categorized as either pathologic complete response ( pCR ) or invasive cells ( pINV ) . Disease-free survival ( DFS ) , distant disease-free survival ( DDFS ) , and survival were estimated through 5 years and compared between treatment groups . In the preoperative arm , proportional-hazards models were used to investigate the relationship between outcome and tumor response . RESULTS There was no significant difference in DFS , DDFS , or survival ( P = .99 , .70 , and .83 , respectively ) among patients in either group . More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy ( 67.8 % v 59.8 % , respectively ) . Rates of ipsilateral breast tumor recurrence ( IBTR ) after lumpectomy were similar in both groups ( 7.9 % and 5.8 % , respectively ; P = .23 ) . Outcome was better in women whose tumors showed a pCR than in those with a pINV , cPR , or cNR ( relapse-free survival [ RFS ] rates , 85.7 % , 76.9 % , 68.1 % , and 63.9 % , respectively ; P < .0001 ) , even when baseline prognostic variables were controlled . When prognostic models were compared for each treatment group , the preoperative model , which included breast tumor response as a variable , discriminated outcome among patients to about the same degree as the postoperative model . CONCLUSION Preoperative chemotherapy is as effective as postoperative chemotherapy , permits more lumpectomies , is appropriate for the treatment of certain patients with stages I and II disease , and can be used to study breast cancer biology . Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases ; however , knowledge of such a response provided little prognostic information beyond that which result ed from postoperative therapy 10515 Background : A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin ( T/C ) with or without trastuzumab ( H ) in women with stage III breast cancer . METHODS Forty-eight of 75 planned primary breast cancer patients ( T3 or T4 , any N , M0 ) , age between 18 and 80 have been enrolled . Four cycles of T ( 75 mg/m2 ) + C ( AUC 6 ) were given every 3 weeks preoperatively . Patients with HER-2 amplified tumors ( FISH + ) were r and omized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively . Tumors were assessed clinical ly at baseline and after neoadjuvant therapy . Cardiac assessment consisted of medical history , EKG and LVEF ( by echocardiogram or MUGA ) at baseline and at the end of neoadjuvant chemotherapy . RESULTS Available data from 45 of 48 enrolled patients showed 49 % ( 22 cases ) with complete clinical response , with 54.5 % being HER-2 ( + ) ( 12 cases ) . Stable disease was seen in one patient who was HER-2 ( - ) ( 2.2 % ) . Of 37 with complete pathology verification , 11 ( 29.7 % ) showed pathologic complete response ( pCR ) of the primary tumor with 5 cases being HER-2 ( + ) . Of the 22 HER-2 ( + ) cases that completed neoadjuvant treatment , 11 received T/C/H and 11 received T/C. pCR was noted in 36.4 % of the T/C/H group and 9 % of the T/C  group . LVEF data is available from 43 patients during the neoadjuvant phase , showing 18.6 
    Output:
    