***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: We evaluated the survival benefit , safety , feasibility , and tolerability of dose-dense ( DD ) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer . R and omised patients ( n=216 ) received DD or conventional-schedule ( CS ) chemotherapy . Dose-dense regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles , then cyclophosphamide 600 mg m−2 , methotrexate 40 mg m−2 , and fluorouracil 600 mg m−2 ( CMF 600/40/600 ) in three 14-day cycles , plus filgrastim 5 μg kg day−1 as growth support in every cycle . Conventional-schedule regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles , then CMF 600/40/600 in three 21-day cycles , plus filgrastim if required . After a median follow-up of 38.4 months , 71 patients ( 33 % ) relapsed or died : DD , 33 patients ( 15 deaths ) ; CS , 38 patients ( 22 deaths ) . Dose dense showed a trend for improved disease-free survival ( DFS ) and overall survival ( OS ) . Four-year rates of DFS and OS were 64 and 85 % for DD , and 58 and 75 % for CS . All seven cycles were administered to 208 patients ( 96 % ) . Rates of cycle delay , discontinuation , dose reduction , and adverse events were similar in both groups . Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF , supported by filgrastim , is safe and improves survival for patients with node-positive breast cancer BACKGROUND Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer . Strategies to improve efficacy include the use of anthracyclines , taxanes , and intensified dose with bone marrow support . PATIENTS AND METHODS Patients received neoadjuvant epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) followed by paclitaxel 175 mg/m(2 ) ( EC→T ) , each 3-weekly for four cycles ( n = 370 ) , or epirubicin 150 mg/m(2 ) followed by paclitaxel 225 mg/m(2 ) with pegfilgrastim followed by CMF ( cyclophosphamide 500 mg/m(2 ) , methotrexate 40 mg/m(2 ) , fluorouracil 600 mg/m(2 ) ) on days 1 and 8 ( E(dd)→T(dd)→CMF ) , each 2-weekly and for three cycles ( n = 363 ) . Patients were r and omly allocated to either simultaneous darbepoetin alfa ( DA ) ( n = 356 ) or none ( n = 377 ) . RESULTS Pathological complete response ( pCR ) rate ( breast ) was higher with E(dd)→T(dd)→CMF , 18.7 % versus 13.2 % with EC→T ; P = 0.043 , ypT0/Tis ; ypN0 was reported in 20.9 % versus 14.3 % respectively ; P = 0.019 . Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate . Mean hemoglobin values maintained higher with DA ( 13.6 versus 12.6 g/dl ) . E(dd)→T(dd)→CMF regimen showed more grade 3 - 4 mucositis , sensory neuropathy , and neurological complaints . Thromboembolic events were more frequent on DA ( 3 % versus 6 % ; P = 0.055 ) . CONCLUSION Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)→T(dd)→CMF was potentially superior to EC→T in terms of pCR . Primary use of DA did not affect pCR BACKGROUND To determine whether a dose-dense regimen improves outcome in early breast cancer patients , we compared outcomes with the same fluorouracil , epirubicin , and cyclophosphamide ( FEC ) chemotherapeutic regimen administered every 3 weeks ( FEC21 ) or administered every 2 weeks ( FEC14 including support with filgrastim , a granulocyte colony-stimulating factor ) in a multicenter phase III r and omized trial . METHODS A total of 1214 patients with early-stage breast cancer were r and omly assigned to receive six cycles of FEC14 ( 604 patients ) or of FEC21 ( 610 patients ) . Study endpoints were overall survival and event-free survival . Associations were assessed by multivariable analysis with adjustment for age ; tumor size ; grade ; proliferative rate ; and menopausal , lymph node , estrogen receptor , and progesterone receptor status . All statistical tests were two-sided . RESULTS Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation ( 26 % ) than those in the FEC21 arm ( 33 % ) ( difference = 7 % , 95 % confidence interval [ CI ] = 2 % to 12 % ; P = .008 ) . FEC14 therapy , compared with FEC21 therapy , was associated with more asthenia ( 36 % versus 29 % , difference = 7 % , 95 % CI = 2 % to 12 % ; P = .01 ) , bone pain ( 33 % versus 4 % , difference = 29 % , 95 % CI = 25 % to 33 % ; P < .001 ) , anemia ( 38 % versus 19 % , difference = 19 % , 95 % CI = 14 % to 24 % ; P < .001 ) , and thrombocytopenia ( 8 % versus 2 % , difference = 6 % , 95 % CI = 4 % to 9 % ; P < .001 ) , but with less leukopenia ( 12 % versus 45 % , difference = 33 % , 95 % CI = 28 % to 37 % ; P < .001 ) . No acute myelogenous leukemia or myelodysplastic syndrome was observed . At a median follow-up of 10.4 years , no statistically significant difference in the hazard of death ( hazard ratio [ HR ] = 0.87 , 95 % CI = 0.67 to 1.13 ) or recurrence ( HR = 0.88 , 95 % CI = 0.71 to 1.08 ) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis . Although the study was underpowered for subset analysis , we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors . CONCLUSION Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer . However , this therapy was not associated with improved outcome , but because of the limited statistical power of our study , we can not rule out a modest improvement in outcome associated with FEC14 therapy PURPOSE Using a 2 x 2 factorial design , we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin ( A ) , paclitaxel ( T ) , and cyclophosphamide ( C ) with concurrent doxorubicin and cyclophosphamide ( AC ) followed by paclitaxel ( T ) for disease-free ( DFS ) and overall survival ( OS ) ; to determine whether the dose density of the agents improves DFS and OS ; and to compare toxicities . PATIENTS AND METHODS A total of 2,005 female patients were r and omly assigned to receive one of the following regimens : ( I ) sequential A x 4 ( doses ) -- > T x 4 -- > C x 4 with doses every 3 weeks , ( II ) sequential A x 4 -- > T x 4 -- > C x 4 every 2 weeks with filgrastim , ( III ) concurrent AC x 4 -- > T x 4 every 3 weeks , or ( IV ) concurrent AC x 4 -- > T x 4 every 2 weeks with filgrastim . RESULTS A protocol -specified analysis was performed at a median follow-up of 36 months : 315 patients had experienced relapse or died , compared with 515 expected treatment failures . Dose-dense treatment improved the primary end point , DFS ( risk ratio [ RR ] = 0.74 ; P = .010 ) , and OS ( RR = 0.69 ; P = .013 ) . Four-year DFS was 82 % for the dose-dense regimens and 75 % for the others . There was no difference in either DFS or OS between the concurrent and sequential schedules . There was no interaction between density and sequence . Severe neutropenia was less frequent in patients who received the dose-dense regimens . CONCLUSION Dose density improves clinical outcomes significantly , despite the lower than expected number of events at this time . Sequential chemotherapy is as effective as concurrent chemotherapy BACKGROUND The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate ( pCR ) in patients with locally advanced breast cancer ( LABC ) treated with combined modality therapy . PATIENTS AND METHODS Stage IIIA/IIIB patients received three courses of induction chemotherapy ( ICT ) with cyclophosphamide , epirubicin and 5-fluorouracil ( CEF ) followed by local therapy ( total mastectomy or segmental mastectomy with axillary nodes dissection ) and adjuvant chemotherapy ( ACT ) with three courses of CEF alternated with three courses of cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) .  Patients were r and omized to receive ICT and ACT every 3 weeks ( arm A , ' st and ard treatment ' ) or every 2 weeks with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) support ( arm B , ' dose-dense treatment ' ) . In both arms radiotherapy was administered after the end of chemotherapy ( in selected cases ) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years . RESULTS A total of 150 patients were r and omized ( 77 arm A and 73 arm B ) and demographics were well balanced between the two arms . Compliance to treatment was excellent : 95 % and 93 % of patients in arms A and B , respectively , completed the treatment program with no modification or delay . Median duration of treatment ( ICT+local+ACT ) was 183 days ( range 0 - 265 ) in arm A and 139 days ( 0 - 226 ) in arm B. The average relative dose intensity ( ARDI ) of chemotherapy was 1.3 with a 30 % increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [ 62 % ; 95 % confidence interval ( CI ) 49 % to 73.2 % ] and pathological response rates to ICT was observed between the two arms . Median follow-up was 5 years ( range 1 - 96 months ) ; median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in st and ard therapy : this figure has not yet been reached in the dose-dense treatment . CONCLUSIONS In LABC a dose-dense regimen , while allowing a 30 % increase in the dose intensity of chemotherapy , did not provide significant improvement in pathological response rates . However , accelerated chemotherapy reduced the duration of the combined-modality program ( 6.1 versus 4.6 months ) with no additional toxicities The pattern of growth of human breast cancer is important theoretically and clinical ly . Speer et al. ( Cancer Res . , 44 : 4124 - 4130 , 1984 ) have recently proposed that all individual tumors initially grow with identical Gompertzian parameters , but subsequently develop kinetic heterogeneity by a r and om time-dependent process . This concept has elicited interest because it fits clinical data for the survival of untreated patients , for the progression of shadows on serial paired mammograms , and for time-to-relapse following mastectomy . The success of these curve-fits is compelling , and the model has been applied to clinical trials . However , the assumption of uniform nascent growth is not supported by theory or data , and individual cancers have not been shown to follow the complex growth curves predicted by the Speer model . As an alternative , if kinetic heterogeneity is understood to be an intrinsic property of neoplasia , the same three historical data sets are fit well by an unadorned Gompertzian model which is parsimonious and has many other intuitive and empirical advantages . The two models differ significantly in such clinical projections as the estimated duration of silent growth prior to diagnosis and the anticipated optimal chemotherapy schedule postsurgery BACKGROUND AND OBJECTIVES Treatment with CHOP chemotherapy in elderly patients with aggressive non-Hodgkin 's lymphoma ( NHL ) is less effective and accompanied by more adverse effects than in younger patients . The 
    Output:
    
No benefit was observed in patients with hormone receptor-positive tumors .
Dose-dense chemotherapy results in better overall and disease-free survival , particularly in women with hormone receptor-negative breast cancer .