***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 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 . ) BACKGROUND The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial . We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes . METHODS Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes . Patients in the conventional-dose group received fluorouracil , epirubicin , and cyclophosphamide ( FEC ) every three weeks for five courses , followed by radiotherapy and tamoxifen . The high-dose treatment was identical , except that high-dose chemotherapy ( 6 g of cyclophosphamide per square meter of body-surface area , 480 mg of thiotepa per square meter , and 1600 mg of carboplatin per square meter ) with autologous peripheral-blood hematopoietic progenitor-cell transplantation replaced the fifth course of FEC . RESULTS Of the 885 patients , 442 were assigned to the high-dose group and 443 to the conventional-dose group . After a median follow-up of 57 months , the actuarial 5-year relapse-free survival rates were 59 percent in the conventional-dose group and 65 percent in the high-dose group ( hazard ratio for relapse in the high-dose group , 0.83 ; 95 percent confidence interval , 0.66 to 1.03 ; P=0.09 ) . In the group with 10 or more positive nodes , the relapse-free survival rates were 51 percent in the conventional-dose group and 61 percent in the high-dose group ( P=0.05 by the log-rank test ; hazard ratio for relapse , 0.71 ; 95 percent confidence interval , 0.50 to 1.00 ) . CONCLUSIONS High-dose alkylating therapy improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes . This benefit may be confined to patients with HER-2/neu-negative tumors PURPOSE In 1992 , the Early Breast Cancer Trialists ' Collaborative Group reported that a meta- analysis of six r and omized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation . Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women . PATIENTS AND METHODS From 1993 to 1999 , we recruited 709 premenopausal women with operable breast cancer ( 652 from Vietnam , 47 from China ) to a r and omized clinical trial of adjuvant oophorectomy and tamoxifen ( 20 mg orally every day ) for 5 years or observation and this combined hormonal treatment on recurrence . At later date s  estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases ( 66 % ) . RESULTS Treatment arms were well balanced . With a median follow-up of 3.6 years , there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group , with 5-year disease-free survival rates of 75 % and 58 % ( P = .0003 unadjusted ; P = .0075 adjusted ) , and overall survival rates of 78 % and 70 % ( P = .041 unadjusted ) for the adjuvant and observation groups , respectively . Only patients with hormone receptor-positive tumors benefited from the adjuvant treatment . In Vietnam , for women unselected for hormone receptor status , a cost-effectiveness analysis suggests that this intervention costs $ 350 per year of life saved . CONCLUSION Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen The aim of this study was to test the hypothesis of Goldie and Coldman that the use of non-cross-resistant regimens of chemotherapy could lead to maximal anti-tumour effect . We compared st and ard CMF ( cyclophosphamide , methotrexate , fluorouracil ) with alternating CMF/EV ( epirubicin , vincristine ) in the adjuvant therapy of early breast cancer . Stage II premenopausal node-positive or post-menopausal node-positive oestrogen receptor-negative and stage III breast cancer patients were eligible for the study . From January 1985 to December 1990 , 220 patients were r and omised ( 115 to CMF and 105 to CMF/EV ) .  Toxicity was mild ; neurotoxicity , vomiting and hair loss were more frequent in the CMF/EV group , while permanent amenorrhoea , diarrhoea , stomach ache and minor infections occurred more often in the CMF arm . At a follow-up of 48 months , 113 patients ( 51.4 % ) had had recurrence ( 62 on CMF and 51 on CMF/EV ) and 54 ( 24.5 % ) had died ( 30 on CMF and 24 on CMF/EV ) . There was no significant difference in disease-free and overall survival between the two arms . After adjusting for menopausal status and stage , the relative risk ( RR ) of recurrence for CMF/EV patients was 0.93 ( 95 % CL 0.64 - 1.35 ) , while the RR of death was 0.85 ( 95 % CL 0.49 - 1.47 ) . In conclusion , the Goldie-Coldman model of alternating therapy is not confirmed in this trial of adjuvant therapy of early breast cancer , although in view of its design a difference of less than 20 % in 3 year disease-free survival could not be excluded The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) implemented protocol B-15 to compare 2 months of Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) and cyclophosphamide ( AC ) with 6 months of conventional cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in patients with breast cancer nonresponsive to tamoxifen ( TAM , T ) . A second aim was to determine whether AC followed in 6 months by intravenous ( IV ) CMF was more effective than AC without reinduction therapy . Through 3 years of follow-up , findings from 2,194 patients indicate no significant difference in disease-free survival ( DFS , P = .5 ) , distant disease-free survival ( DDFS , P = .5 ) or survival ( S , P = .8 ) among the three groups . Since the outcome from AC and CMF was almost identical , the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients . AC seems preferable since , following total mastectomy , AC was completed on day 63 versus day 154 for conventional CMF ; patients visited health professionals three times as often for conventional CMF as for AC ; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF ; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC . The difference in the amount of alopecia between the two treatment groups was less than anticipated . While alopecia was almost universally observed following AC therapy , 71 % of the CMF patients also had hair loss and , in 41 % , the loss was greater than 50 % . This study and NSABP B-16 , which evaluates the worth of AC therapy in TAM-responsive patients , indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients 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 % CI=0.75 - 1.23 ) , P=.74 ; survival : RR = 0.90 ( 95 % CI=0.69 - 1.19 ) , P=.47 ; RFS : RR=0.88 ( 95 % CI=0.67 - 1.16 ) , P=.37 ; DDFS : RR=1.03 ( 95 % CI=0.79 - 1.35 ) , P=.84 . Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS ( P=.02 ) and DDFS ( P=.02 ) but not for survival ( P= .15 ) or RFS ( P=.06 ) . CON 
    Output:
    
HER2/neu overexpression and /or amplification was associated with greater efficacy of the anthracycline or taxane regimen .
Conclusions Current evidence supports the conclusion that the benefit of both anthracycline-based and taxane-based adjuvant chemotherapy is associated on HER2/neu status , with patients with HER2/neu-positive cancers benefiting more from these therapies than those with HER2/neu-negative cancers