***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 : There are currently no vali date d factors predictive of response to taxanes in patients with breast cancer . We analyzed specimens from patients included in the Breast Cancer International Research Group ( BCIRG ) 001 trial , a r and omized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival ( DFS ) and overall survival ( OS ) . Experimental Design : Immunohistochemical assessment of biological markers included histologic grade , tumor size , estrogen and progesterone receptors , lymph node status , HER2 , MUC1 , Ki-67/MIB-1 , p53 , Bcl-2 , Bax , Bcl-XL , BAG-1 , β-tubulin isotypes II , III and IV , τ protein , and detyrosinated α tubulin . Associations between selected parameters and survival were tested through univariate analyses , then completed with multivariate analyses and a bootstrap resampling technique . Results : In univariate analysis histologic grade , tumor size , number of involved nodes , estrogen and progesterone receptor status , p53 , Ki-67 , tubulin III , and τ protein were associated both with DFS and with OS . In multivariate analysis estrogen and progesterone receptors , tumor size , number of involved nodes , and Ki-67 protein were associated both with DFS and with OS , whereas τ protein levels were correlated with DFS and tubulin III and P53 were correlated with OS . No interaction was observed between Ki-67 and treatment allocation . Conclusions : We conclude that the expression in primary tumors of Ki-67 and p53 protein , as well as of the microtubule-related parameters τ protein and tubulin III , are independent prognostic factors in patients receiving adjuvant chemotherapy  for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy . Clin Cancer Res ; 16(15 ) ; 3988–97 . © 2010 AACR Purpose : To assess the predictive value of Ki67 expression in postmenopausal hormone receptor – positive early-breast cancer patients , who were either treated  with adjuvant tamoxifen ( TAM ) alone or with TAM followed by anastrozole ( ANA ) . Experimental Design : Expression of Ki67 was determined central ly by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospect ively r and omized Austrian Breast and Colorectal Cancer Study Group Trial 8 , and had received TAM for 5 years , or TAM for 2 years followed by ANA for 3 years  . Ki67 expression was evaluated both as a continuous variable and dichotomized to low ( ≤10 % ) and high ( > 10 % ) . Recurrence-free survival ( RFS ) and overall survival ( OS ) were analyzed using Cox models adjusted for clinical and pathologic parameters . Results : Patients with a high Ki67 expression ( 394/1,587 ; 23 % ) had a significantly shorter RFS ( adjusted HR for recurrence = 1.90 , 95 % CI : 1.37–2.64 , P = 0.0001 ) and OS ( adjusted HR for death = 1.78 , 95 % CI : 1.18–2.70 , P = 0.006 ) . In women with breast tumors expressing medium or high ER levels ( n = 1,438 ) , the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS ( P = 0.03 ) . TAM followed by ANA was superior to TAM alone in patients with low Ki67 ( adjusted HR = 0.53 , 95 % CI : 0.34–0.83 , P = 0.005 ) but not in high Ki67 disease ( adjusted HR = 1.18 , 95 % CI : 0.66–1.89 , P = 0.68 ) . Conclusions : Adjuvant sequencing of TAM and ANA is superior to TAM alone , particularly in postmenopausal women with medium or high ER expressing , low proliferating breast cancer . Clin Cancer Res ; 17(24 ) ; 7828–34 . © 2011 AACR Introduction The PACS01 trial has demonstrated that a docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival ( DFS ) and overall survival of node-positive early breast cancer ( EBC ) . We search ed for prognostic and predictive markers for docetaxel 's benefit . Methods Tumor sample s from 1,099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry . The prognostic and predictive values of each marker and four molecular subtypes ( luminal A , luminal B , HER2-overexpressing , and triple-negative ) were tested . Results Progesterone receptor-negativity ( HR = 0.66 ; 95 % CI 0.47 to 0.92 , P = 0.013 ) , and Ki67-positivity ( HR = 1.53 ; 95 % CI 1.12 to 2.08 , P = 0.007 ) were independent adverse prognostic factors . Out of the 34 proteins , only Ki67-positivity was associated with DFS improvement with docetaxel addition ( adjusted HR = 0.51 , 95 % CI 0.33 to 0.79 for Ki67-positive versus HR = 1.10 , 95 % CI 0.75 to 1.61 for Ki67-negative tumors , P for interaction = 0.012 ) . Molecular subtyping predicted the docetaxel benefit , but without providing additional information to Ki67 status . The luminal A subtype did not benefit from docetaxel ( HR = 1.16 , 95 % CI 0.73 to 1.84 ) ; the reduction in the relapse risk was 53 % ( HR = 0.47 , 95 % CI 0.22 to 1.01 ) , 34 % ( HR = 0.66 , 95 % CI 0.37 to 1.19 ) , and 12 % ( HR = 0.88 , 95 % CI 0.49 to 1.57 ) in the luminal B , HER2-overexpressing , and triple-negative subtypes , respectively . Conclusions In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy  , the most powerful predictor of docetaxel benefit is Ki67-positivity BACKGROUND This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high-risk breast cancer ( HRBC ) patients with > 9 involved lymph nodes , who received different chemotherapy dose-intensification strategies within a prospect i ve r and omized WSG AM-01 trial . MATERIAL S AND METHODS Paraffin-embedded tumors from 236 patients , who were r and omly assigned to dose-dense conventional chemotherapy with four cycles of E(90)C(600  ) followed by three cycles of C(600)M(40)F(600 ) every 2 weeks ( DD ) or a rapidly cycled t and em high-dose regimen  with two cycles of E(90)C(600 ) every 2 weeks followed by two cycles of  E(90)C(3000)Thiotepa(400  ) every 3 weeks ( HD ) , were available for retrospective central pathological review ( 116 HD/120 DD ) . Expression of estrogen receptor ( ER ) , progesterone receptor ( PR ) , MIB-1 , epidermal growth factor receptor , and Her-2/neu was evaluated immunohistochemically using tissue microarrays . Results were correlated with follow-up data and treatment effects by proportional hazard Cox regression models ( including interaction analysis ) . RESULTS After a median follow-up of 61.7 months , 5-year event-free survival ( EFS ) as well as overall survival ( OS ) rates for the 236 patients were significantly better in the HD arm : EFS : 62 % versus 41 % [ hazard ratio ( HR ) = 0.60 , 95 % CI 0.43 - 0.85 , P = 0.004 ] ; OS : 76 % versus 61 % ( HR = 0.58 , 95 % CI 0.39 - 0.87 , P = 0.007 ) . In multivariate analysis , HD , tumor size <3 cm , positive PR , negative MIB-1 staining , and grade 1/2 were associated with favorable outcome . Interaction analysis showed that regarding predictive effects , triple negative ( ER/PR/Her-2/neu ) and G3 tumors derived most benefit from HD . CONCLUSION T and em HD improves both EFS and OS in HRBC . This therapy effect may be partly attributable to superior efficacy in the subgroup of triple-negative tumors and /or G3 with their poor prognostic marker profile Overexpression of G1-S regulators cyclin D1 or cyclin A is frequently observed in breast cancer and is also to result in lig and -independent activation of oestrogen receptor in vitro . This might therefore , provide a mechanism for failure of tamoxifen treatment . We examined by immunohistochemical staining the effect of deregulation of these , and other cell cycle regulators on tamoxifen treatment in a group of 394 patients with early stage breast cancer . In univariate analysis , expression of cyclin A , Neu , Ki-67 index , and lack of OR expression were significantly associated with worse prognosis . When adjusted by the clinical model ( for lymph node status , age , performance status , T-classification , grade , prior surgery , oestrogen receptor status and tamoxifen use ) , only overexpression of cyclin A and Neu were significantly associated with worse prognosis with hazard ratios of , respectively , 1.709 ( P=0.0195 ) and 1.884 ( P=0.0151 ) . Overexpression of cyclin A was found in 86 out of the 201 OR-positive cases treated with tamoxifen , and was the only independent marker associated with worse prognosis ( hazard ratio 2.024 , P=0.0462 ) . In conclusion , cyclin A is an independent predictor of recurrence of early stage breast cancer and is as such a marker for response in patients treated with tamoxifen Clinicians have traditionally used clinicopathological ( CP ) factors to determine locoregional recurrence ( LR ) risk of breast cancer and have generated the IBTR ! nomogram to predict the risk of ipsilateral breast tumor recurrence ( IBTR ) . The 21-gene recurrence score ( RS ) assay was recently correlated with LR in retrospective studies . The objective of this study was to examine the relationship between the RS and IBTR!. CP characteristics of 308 consecutive patients who underwent RS testing at our institution were examined . IBTR ! was used to estimate the risk of 10-year IBTR . Descriptive statistics were used to compare the RS with the estimated IBTR!. Given a low event rate in this cohort , actual IBTR rates were not reported . Most patients had stage I/II ( 98 % ) and grade I/II ( 77 % ) disease . Median age was 54 years ( range , 30–78 ) .  Median IBTR ! without radiation therapy was 10 % ( mean , 12 % [ range , 4 - 43 % ] ) . RS was low ( < 18 ) , intermediate ( 18–30 ) , and high ( > 30 ) in 52 % ( n = 160 ) , 40 % ( n = 123 ) , and 8 % ( n = 25 ) patients . Overall , IBTR ! did not correlate with RS ( P = .77 ) . We saw no correlation between RS and IBTR ! in patients with less than ( P = .32 ) or greater than ( P = .48 ) a 10 % risk of IBTR . Interestingly , Ki-67 expression correlated with both IBTR ! ( P = .019 ) and the RS ( P = .002 ) . Further study is warranted to determine if the RS can provide complementary biological information to CP factors in estimating the risk of LR . Prospect i ve studies evaluating this association may potentially allow for individualized treatment decisions Summary In 1982 we constructed a prognostic index for patients with primary , operable breast cancer . This index was based on a retrospective analysis of 9 factors in 387 patients . Only 3 of the factors ( tumour size , stage of disease , and tumour grade ) remained significant on multivariate analysis . The index was subsequently vali date d in a prospect i ve study of 320 patients . We now present the results of applying this prognostic index to all of the first 1,629 patients in our series of operable breast cancer up to the age of 70 . We have used the index to define three subsets of patients with different chances of dying from breast cancer : 1 ) good prognosis , comprising 29 % of patients with 80 % 15-year survival ; 2 ) moderate prognosis , 54 % of patients with 42 % 15-year survival ; 3 ) poor prognosis , 17 % of patients with 13 % 15-year survival . The 15-year survival of an age-matched female population was 83 % PURPOSE The indications of 
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We conclude that Ki-67 has an independent prognostic value in terms of OS in BC patients .
The Ki-67 threshold with the greatest prognostic significance is as yet unknown , but a cut-off > 25 % is associated with a greater risk of death compared with lower expression rates