***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: Introduction The HOXB13:IL17BR index has been identified to predict clinical outcome in the setting of adjuvant tamoxifen monotherapy of breast cancer . Further studies have shown that HOXB13 in particular can indicate benefit of prolonged tamoxifen treatment . Patients with high-expressing tumors did not benefit from prolonged treatment , suggesting that HOXB13 might be involved in tamoxifen resistance . No studies have been made regarding the HOXB13 protein levels in breast cancer . The aim of our study was to investigate whether tamoxifen benefit can be correlated to different levels of HOXB13 protein expression . Methods We used immunohistochemistry to analyze protein levels of HOXB13 in tumor sample s from 912 postmenopausal node-negative breast cancer patients r and omized to adjuvant tamoxifen therapy or no endocrine treatment .  Results Tamoxifen-treated patients with estrogen receptor-positive tumors expressing none or low levels of HOXB13 had a clear benefit from tamoxifen in terms of longer distant recurrence-free survival ( DRFS ) ( hazard ratio = 0.38 , 95 % confidence interval = 0.23 to 0.60 , P = 0.000048 ) . However , for patients with a high or intermediate HOXB13 tumor expression , tamoxifen did not prolong the DRFS compared with the untreated patients ( hazard ratio = 0.88 , 95 % confidence interval = 0.47 to 1.65 , P = 0.69 ) . Interaction between HOXB13 expression and benefit from tamoxifen  was statistically significant for DRFS ( P = 0.035 ) . No prognostic value could be ascribed to HOXB13 among systemically untreated patients . Conclusions A high HOXB13 expression was associated with decreased benefit from tamoxifen , which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment 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 70-gene prognosis-signature is a prognostic tool for early breast cancer analysis . In addition to scientific evidence , implementation of the signature in clinical trials and daily practice requires logistical feasibility . The aim of our study was to test logistics for gene expression profiling on fresh frozen tumour tissue in the preparation for the prospect i ve , multinational Microarray In Node-negative Disease may Avoid ChemoTherapy ( MINDACT ) trial . METHODS Sixty-four patients were included in six European hospitals .  Fresh frozen tumour sample s were shipped on dry ice to Agendia B.V. , where RNA was isolated and subsequently hybridised on the 70-gene prognosis-signature ( MammaPrint ) . RESULTS Tumour sample s were obtained in 60 of 64 patients . Among the 60 sample s , 11 contained insufficient tumour cells ( < 50 % ) and three contained insufficient RNA quality . All 46 sample s eligible for genomic profiling were successfully hybridised , and the results were reported on average within 4 - 5d . CONCLUSION Gene expression profiling on fresh frozen tissue is feasible in daily clinical practice Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment . We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy . Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6 ; treatment order was r and omly assigned . Pretreatment core biopsy sample s were interrogated for genes that might correlate with pathologic complete response ( pCR ) . In addition to the individual genes , the correlation of the Oncotype DX Recurrence Score with pCR was examined . Results Of 70 patients enrolled in the parent trial , core biopsies sample s with sufficient RNA for gene analyses were available from 45 patients ; 9 ( 20 % ) had inflammatory breast cancer ( IBC ) . Six ( 14 % ) patients achieved a pCR . Twenty-two of the 274 c and i date genes assessed correlated with pCR ( p < 0.05 ) . Genes correlating with pCR could be grouped into three large clusters : angiogenesis-related genes , proliferation related genes , and invasion-related genes . Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR . In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer ; twenty-four ( 9 % ) of the genes were differentially expressed ( p < 0.05 ) , 5 were upregulated and 19 were downregulated in IBC . Conclusion Gene expression analysis on core biopsy sample s is feasible and identifies c and i date genes that correlate with pCR to primary chemotherapy . Gene expression in IBC differs significantly from noninflammatory breast cancer Introduction Patients with early-stage breast cancer , treated with endocrine therapy  , have approximately 90 % 5-year disease-free survival . However , for patients at higher risk of relapse despite endocrine therapy , additional adjuvant therapy , such as chemotherapy , may be indicated . The challenge is to prospect ively identify such patients . The Mammostrat ® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions . We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up . Methods Tissue microarrays from a consecutive series ( 1981 to 1998 ) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review . Of 1,390 cases stained , 197 received no adjuvant hormonal or chemotherapy , 1,044 received tamoxifen only , and 149 received a combination of hormonal therapy and chemotherapy . Median age at diagnosis was 57 , 71 % were postmenopausal , 23.9 % were node-positive and median tumor size was 1.5 cm . Sample s were stained using triplicate 0.6 mm2 tissue microarray cores , and positivity for p53 , HTF9C , CEACAM5 , NDRG1 and SLC7A5 was assessed . Each case was assigned a Mammostrat ® risk score , and distant recurrence-free survival ( DRFS ) , relapse-free survival ( RFS ) and overall survival ( OS ) were analyzed by marker positivity and risk score . Results Increased Mammostrat ® scores were significantly associated with reduced DRFS , RFS and OS in estrogen receptor (ER)-positive breast cancer ( P < 0.00001 ) . In multivariate analyses the risk score was independent of conventional risk factors for DRFS , RFS and OS ( P < 0.05 ) . In node-negative , tamoxifen-treated patients , 10-year recurrence rates were 7.6 ± 1.5 % in the low-risk group versus 20.0 ± 4.4 % in the high-risk group . Further , exploratory analyses revealed associations with outcome in both ER-negative and untreated patients . Conclusions This is the fifth independent study providing evidence that Mammostrat ® can act as an independent prognostic tool for ER-positive , tamoxifen-treated breast cancer . In addition , this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors . When viewed in the context of previous results , these data provide further support for this antibody panel as an aid to patient  management  in early-stage breast cancer Background The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients . We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients . A further objective was to investigate any prognostic effects of the ratio in systematic ally untreated premenopausal patients . Based on the current knowledge of HOXB13 and IL17BR , we hypothesized that these genes may have individual prognostic or predictive power . Patients and methods  Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 r and omized postmenopausal patients and 93 systemically untreated premenopausal patients . Results A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics , as were low levels of IL17BR alone . The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment , with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio ( recurrence rate ratio : RR = 0.39 ; P = 0.030 ) , or low expression of HOXB13 ( RR = 0.37 ; P = 0.015 ) . No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups . The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis . In the systemically untreated cohort , only IL17BR showed independent prognostic significance . Conclusion We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy , with a high ratio or a high expression rendering patients less likely to respond . We have also shown that IL17BR might be an independent prognostic factor in 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 ass 
    Output:
    
The 5-antibody immunohistochemistry panel and 70-gene signature satisfied Level II evidence for estimating DRR and OS .
Adjuvant !
Online satisfied Level II evidence for estimating DRR , OS , and chemotherapy response .
The 5-gene expression index satisfied Level III evidence for predicting DRR .