***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 
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    Input: BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer PURPOSE The 21-gene Recurrence Score ( RS ) assay has been vali date d to quantify the risk of distant recurrence in tamoxifen-treated patients with lymph node-negative , estrogen receptor-positive breast cancer and predict magnitude of chemotherapy benefit . This multicenter study was design ed to prospect ively examine whether RS affects physician and patient adjuvant treatment selection and satisfaction . PATIENTS AND METHODS Before and after obtaining the 21-gene RS assay , medical oncologists stated their adjuvant treatment recommendation and confidence in it . Patients also indicated their treatment choice pre- and post-RS assay . Patients completed measures for decisional conflict , anxiety , and quality of life . RESULTS Seventeen medical oncologists at one community and three academic practice s consecutively enrolled 89 assessable patients . The medical oncologist treatment recommendation changed for 28 patients ( 31.% ) . Twenty-four patients ( 27 % ) changed their treatment decision . The largest change after the RS results was conversion from the medical oncologist 's pretest recommendation for chemotherapy plus hormonal therapy ( CHT ) to post-test recommendation for hormone therapy ( HT ) in 20 cases ( 22.5 % ) . Nine patients ( 10.1 % ) changed their treatment decision from CHT to HT . RS results increased medical oncologist confidence in their treatment recommendation in 68 cases ( 76 % ) . Patient anxiety and decisional conflict were significantly lower after RS results . CONCLUSION The results of this study indicate that the RS assay impacts medical oncologist adjuvant treatment recommendations , patient treatment choice , and patient anxiety Novel genetic profiling tests of breast cancer tissue have been shown to be prognostic for overall survival and predictive of local and distant rates of recurrence in breast cancer patients . One of these tests , Oncotype DXtrade mark , is a diagnostic test comprised of a 21-gene assay applied to paraffin-embedded breast cancer tissue , which allows physicians to predict subgroups of hormone-receptor-positive , node-negative patients who may benefit from hormonal therapy alone or require adjuvant chemotherapy  to attain the best survival outcome . The results of the assay are converted to a recurrence score ( 0 - 100 ) that has been found to be predictive of 10- and 15-year local and distant recurrence in node-negative , estrogen-receptor-positive breast cancer patients . Previous studies have shown that patients with high recurrence scores benefit from adjuvant chemotherapy , whereas patients with low recurrence scores do not . To evaluate the ability to guide treatment decisions in the group with a mid-range recurrence score , the North American Cooperative Groups developed the Trial Assessing IndiviuaLized Options for Treatment for breast cancer , a r and omized trial of chemotherapy followed by hormonal therapy versus hormonal therapy alone on invasive disease-free survival-ductal carcinoma in situ ( IDFS-DCIS ) survival in women with node-negative , estrogen-receptor-positive breast cancer with a recurrence score of 11 - 25 . The study was initiated in May 2006 and approximately 4500 patients will be r and omized . This article describes the rationale , methodology , statistical ana-lysis and implication s of the results on clinical practice The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies BACKGROUND A microarray-based 70-gene prognosis signature might improve the selection of patients with node-negative breast cancer for adjuvant systemic treatment .  The main aims of this MicroarRAy PrognoSTics in Breast CancER ( RASTER ) study were to assess prospect ively the feasibility of implementation of the 70-gene prognosis signature in community-based setting s and its effect on adjuvant systemic treatment decisions when considered with treatment advice formulated from the Dutch Institute for Healthcare Improvement ( CBO ) and other guidelines . METHODS Between January , 2004 and December , 2006 , 812 women aged under 61 years with primary breast carcinoma ( clinical T1 - 4N0M0 ) were enrolled . Fresh tumour sample s were collected in 16 hospitals in the Netherl and s within 1 h after surgery . Clinicopathological factors were collected and microarray analysis was done with a custom- design ed array chip that assessed the mRNA expression index of the 70 genes previously identified for the prognostic signature . Patients with a " good " signature were deemed to have a good prognosis and , therefore , could be spared adjuvant systemic treatment with its associated adverse effects , whereas patients with a " poor " signature were judged to have a poor prognosis and should be considered for adjuvant systemic treatment .  Concordance between risk predicted by the prognosis signature and risk predicted by commonly used clinicopathological guidelines ( ie , St Gallen guidelines , Nottingham Prognostic Index , and Adjuvant ! Online ) was assessed . FINDINGS Of 585 eligible patients , 158 patients were excluded because of sampling failure ( n=128 ) and incorrect procedure ( n=30 ) . Prognosis signatures were assessed in 427 patients . The 70-gene prognosis signature identified 219 ( 51 % ) patients with good prognosis and 208 ( 49 % ) patients with poor prognosis . The Dutch CBO guidelines identified 184 patients ( 43 % ) with poor prognosis , which was discordant with those findings obtained with the prognosis signature in 128 ( 30 % ) patients . Oncologists recommended adjuvant treatment in 203 ( 48 % ) patients based on Dutch CBO guidelines , in 265 ( 62 % ) patients if the guidelines were used with the prognosis signature , and in 259 ( 61 % ) patients if Dutch CBO guidelines , prognosis signature , and patients ' preferences for treatment were all taken into account . Adjuvant ! Online guidelines identified more patients with poor prognosis than did the signature alone ( 294 [ 69 % ] ) , and discordance with the signature occurred in 160 ( 37 % ) patients . St Gallen guidelines identified 353 ( 83 % ) patients with poor prognosis with the signature and discordance in 168 ( 39 % ) patients . Nottingham Prognostic Index recorded 179 ( 42 % ) patients with poor prognosis with the signature and discordance in 117 ( 27 % ) patients . INTERPRETATION Use of the prognosis signature is feasible in Dutch community hospitals . Adjuvant systemic treatment was advised less often when the more restrictive Dutch CBO guidelines were used compared with that finally given after use of the prognosis signature . For the other guidelines assessed , less adjuvant chemotherapy would be given when the data based on prognosis signature alone are used , which might spare patients from adverse effects and confirms previous findings . Future studies should assess whether use of the prognosis signature could improve survival or equal survival while avoiding unnecessary adjuvant systemic treatment without affecting patients ' survival , and further assess the factors that physicians use to recommend adjuvant systemic treatment The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction ( RT‐PCR ) assay underwent validation in 668 lymph node‐negative , estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program ( NSABP ) B‐14 . The predictive accuracy for treatment efficacy also underwent validation in 651 patients r and omized on NSABP B‐20 and 645 patients on NSABP B‐14 BACKGROUND The MINDACT ( Microarray In Node-negative and 1 - 3 node positive Disease may Avoid  ChemoTherapy )  trial investigates the clinical utility of the 70-gene profile ( MammaPrint ) for the selection of breast cancer patients for adjuvant chemotherapy ( CT )  together with st and ard clinicopathological criteria . We present the results of the pilot phase consisting of first 800 patients included . METHODS MINDACT has enrolled 6600 patients , classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant ! Online . Patients with both clinical ( C ) and genomic ( G ) high risks are offered adjuvant CT ; those with both C and G low risks do not receive CT ; patients with discordant risk are r and omised for the decision of adjuvant CT based on C or G risk . CT r and omisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy r and omisation between letrozole and tamoxifen→letrozole are offered . RESULTS During the pilot phase 46 % of screened patients were enrolled . Main reasons for non-enrolment were node positivity before trial amendment , sample quality problems and failure to meet logistic setting s. Among the 800 patients , 386 ( 48 % ) were C-low/G-low , 198 ( 24.8 % ) as C-high/G-high , 75 ( 9.4 % ) as C-low/G-high and 141 ( 17.6 % ) as C-high/G-low . In total 216 ( 27 % ) cases were discordant . The difference between patients with C-high ( 42 % ) and G-high risk ( 34 % ) is 8.25 % ( 95 % confidence interval ( CI ) , 4.7 - 11.8 % ; P<.0001 ) . Compliance with the treatment decision was high ( > 92 % ) . CONCLUSIONS The logistically complex MINDACT trial is feasible in a multinational setting . The proportion of discordant patients , the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospect i ve neoadjuvant endocrine therapy ( NAET ) with tamoxifen or anastrozole  to determine if the 21-gene recurrence score ( RS ) predicts NAET responses . RS scores were determined from pretreatment core biopsy specimens . Although half of the specimens yielded insufficient RNA , the remaining sample s were highly representative . Patients with a low RS tended to respond better than those with an intermediate or high RS ( n=43 ) . Response 
    Output:
    
Indirect evidence showed Oncotype DX was able to predict treatment effects of adjuvant chemotherapy , whereas no evidence of predictive value was found for MammaPrint .
The cost-effectiveness of Oncotype DX varied with the alternative compared .
For MammaPrint , lack of evidence of the predictive value led to uncertainty in the cost-effectiveness .
Conclusion : No studies were identified that provided direct evidence that using gene-expression profiling tests to direct treatment decisions improved outcomes in women with breast cancer .