***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 This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a  doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer BACKGROUND The purpose was to compare disease-free survival ( DFS ) between epirubicin-based chemoendocrine therapy and tamoxifen alone in one to three node-positive ( N1 - 3 ) , estrogen-receptor-positive ( ER+ ) , postmenopausal early breast cancer ( EBC ) patients . PATIENTS AND METHODS We analyzed , retrospectively , 457 patients r and omized in FASG 02 and 07 trials who received : tamoxifen alone ( 30 mg/day , 3 years ) ; or FEC50 ( fluorouracil 500 mg/m2 , epirubicin 50 mg/m2 , cyclophosphamide 500 mg/m2 , six cycles every 21 days ) plus tamoxifen started concurrently . Radiotherapy was delivered after the third cycle in FASG 02 trial , and after the sixth in FASG 07 trial . RESULTS The 9-year DFS rates were 72 % with tamoxifen and 84 % with FEC50-tamoxifen ( P = 0.008 ) . The multivariate analysis showed that pathological tumor size > 2 cm was an independent prognostic factor ( P = 0.002 ) , and treatment effects remained significantly in favor of chemoendocrine therapy ( P = 0.0008 ) . The 9-year overall survival rates were 78 % and 86 % , respectively ( P = 0.11 ) . In the multivariate model , there was a trend in favor of chemoendocrine therapy ( P = 0.07 ) . CONCLUSION The addition of FEC50 adjuvant chemotherapy to tamoxifen significantly improves long-term DFS in N1 - 3 , ER+ and postmenopausal women . Chemoendocrine therapy seems to be more effective than tamoxifen in terms of long-term survival BACKGROUND Amplification of the human epidermal growth factor receptor type 2 ( HER2 , also called HER2/neu ) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens . METHODS In the r and omized , controlled Mammary.5 trial , we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide , epirubicin , and fluorouracil ( CEF ) or cyclophosphamide , methotrexate , and fluorouracil ( CMF ) as adjuvant chemotherapy .  HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization , immunohistochemical analysis , and polymerase-chain-reaction analysis . RESULTS Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment . In patients whose tumors showed amplification of HER2 , CEF was superior to CMF when assessed on the basis of relapse-free survival ( hazard ratio , 0.52 ; 95 percent confidence interval , 0.34 to 0.80 ; P=0.003 ) and overall survival ( hazard ratio , 0.65 ; 95 percent confidence interval , 0.42 to 1.02 ; P=0.06 ) . For women whose tumors lacked amplification of HER2 , CEF did not improve relapse-free survival ( hazard ratio for relapse , 0.91 ; 95 percent confidence interval , 0.71 to 1.18 ; P=0.49 ) or overall survival ( hazard ratio for death , 1.06 ; 95 percent confidence interval , 0.83 to 1.44 ; P=0.68 ) . The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival ( 95 percent confidence interval , 1.15 to 3.36 ; P=0.01 ) and 2.04 for overall survival ( 95 percent confidence interval , 1.14 to 3.65 ; P=0.02 ) . CONCLUSIONS Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy . ( cancer.gov number , NCI-V90 - 0027 . ) PURPOSE To determine the influence of the epirubicin dose in operable node-positive breast cancer patients with factors of poor prognosis . PATIENTS AND METHODS Between April 1990 and July 1993 , 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade > or = 2 and hormone receptor negativity were r and omized after surgery to receive either fluorouracil 500 mg/m(2 ) , epirubicin 50 mg/m(2 ) , and cyclophosphamide 500 mg/m(2 ) every 21 days for six cycles ( FEC 50 ) or the same regimen except with epirubicin dose of 100 mg/m(2 ) ( FEC 100 ) . Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemotherapy . Radiotherapy was delivered at the end of chemotherapy in both groups . RESULTS The median follow-up was 67 months . The 5-year disease-free survival ( DFS ) was 54.8 % with FEC 50 and 66.3 % with FEC 100 ( P = .03 ) . The 5-year overall survival ( OS ) was 65.3 % and 77.4 % , respectively ( P = .007 ) . The mean relative dose-intensity was similar in the two groups ( 90.3 % and 86.1 % , respectively ) . Neutropenia and anemia were significantly more frequent in FEC 100 ( P < 10(-3 ) ) , as were nausea-vomiting ( P = .008 ) and stomatitis and alopecia ( P < 10(-3 ) ) . Nine cases of grade 3 infection occurred only with FEC 100 , and no toxic deaths occurred . Three cases of acute cardiac toxicity were observed ( FEC50 = 1 , FEC100 = 2 ) and 10 patients ( FEC50 = 6 , FEC100 = 4 ) presented delayed cardiac dysfunctions . Two cases of secondary leukemia were observed ( acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100 ) . CONCLUSION After 5 years of follow-up , the increased epirubicin dose led to a significant benefit in terms of DFS and OS , with a high survival rate among patients with poor-prognosis breast cancer No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients . We retrospectively evaluated this role in patients enrolled in a phase III study comparing st and ard FEC21 ( 5-fluorouracil , epirubicin , and cyclophosphamide , administered every 3 weeks ) vs dose-dense FEC14 ( the same regimen repeated every 2 weeks )  . HER2 status was determined for 731 of 1214 patients . Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival ( EFS ) and overall survival ( OS ) ; EFS and OS were compared within each HER2 subgroup and within each treatment arm . Median follow-up was 6.7 years . Among FEC21-treated patients , both EFS ( HR=2.07 ; 95 % CI 1.27–3.38 ) and OS ( HR=2.47 ; 95 % CI 1.34–4.57 ) were significantly worse in HER2 + patients than in HER2 − patients . Among FEC14-treated patients , differences in either EFS ( HR=1.21 ; 95 % CI 0.65–2.24 ) or OS ( HR=1.85 ; 95 % CI 0.88–3.89 ) between HER2 + and HER2 − patients were not statistically significant . Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS . Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospect i ve studies BACKGROUND Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin . A retrospective study was design ed to test this hypothesis . METHODS In National Surgical Adjuvant Breast and Bowel Project protocol B-11 , patients with axillary lymph node-positive , hormone receptor-negative breast cancer were r and omly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil ( PF ) or a combination of L-phenylalanine mustard , 5-fluorouracil , and doxorubicin ( PAF ) . Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients . Statistical analyses were performed to test for interaction between treatment and erbB-2 status ( positive versus negative ) with respect to disease-free survival ( DFS ) , survival , recurrence-free survival ( RFS ) , and distant disease-free survival ( DDFS ) . Reported P values are two-sided . RESULTS Overexpression of erbB-2 ( i.e. , positive immunohistochemical staining ) was observed in 239 ( 37.5 % ) of the 638 tumors studied . Overexpression was associated with tumor size ( P=.02 ) , lack of estrogen receptors ( P=.008 ) , and the number of positive lymph nodes ( P=.0001 ) . After a mean time on study of 13.5 years , the clinical benefit from doxorubicin ( PAF versus PF ) was statistically significant for patients with erbB-2-positive tumors -- DFS : relative risk of failure (RR)=0.60 ( 95 % confidence interval [CI]=0.44 - 0.83 ) , P=.001 ; survival : RR=0.66 ( 95 % CI=0.47 - 0.92 ) , P = .01 ; RFS : RR=0.58 ( 95 % CI=0.42 - 0.82 ) , P=.002 ; DDFS : RR=0.61 ( 95 % CI=0.44 - 0.85 ) , P=.003 . However , it was not significant for patients with erbB-2-negative tumors-DFS : RR=0.96 ( 95 % 
    Output:
    
The published data suggest that nonanthracycline alternatives are less toxic than anthracycline-containing regimens and equally , if not more , efficacious .