***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 .To provide a practical quantitative tool for appraising the quality of  cost-effectiveness ( CE ) studies . Methods .A committee comprised of health economists selected a set of criteria for the instrument from an item pool . Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a r and om effects regression model . To vali date the grading system , a survey was sent to 60 individuals with health economics expertise . Participants first rated the quality  of three CE studies  on a visual analogue scale , and then evaluated each study using the  grading system . Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance ( ANCOVA ) for discriminant validity . Agreement between the global rating by experts and the grading system was also examined . Results .Sixteen criteria were selected . Their coefficient estimates ranged from 1.2 to 8.9 , with a sum of 93.5 on a 100-point scale . The only insignificant criterion was “ use of subgroup analyses . ” Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho ( correlation coefficient = 0.78 , P < 0.0001 ) , Wilcoxon test ( P = 0.53 ) , and ANCOVA ( F3,146 = 5.97 , P = 0.001 ) . The grading system had good agreement with global rating by experts . Conclusions . The instrument appears to be simple , internally consistent , and valid for measuring the perceived quality of CE studies . Applicability for use in clinical and re source allocation decision-making deserves further study Background Breast cancer is the most commonly diagnosed non-skin cancer and second leading cause of cancer deaths among women in the US . This study compared healthcare re source utilization and costs in women with breast cancer to a control group in a managed care population . Material and methods Women ≥ 18 years with breast cancer were identified using ICD-9 codes from cl aims data bases of five US health plans during 2004 . A r and omly matched  control group of women without cancer served as a comparator group . Healthcare costs included all medical and pharmacy costs during the year . Comparisons were made using per patient per month ( PPPM ) costs ( total costs per patient within 2004 calendar year/months of eligibility ) . Results 10,697 women ( mean age 55 years ) with breast cancer were identified ( prevalence of 250 per 100,000 ) in 2004 , with prevalence increasing with age  . Mean attributable PPPM costs associated with breast cancer were $ 2,896 ( median = $ 1,940 ) with hospitalization contributing most of the costs ( $ 1,340 ) , followed by pharmacotherapy ( $ 537 ) , and surgical intervention ( $ 470 ) . Mean unadjusted all-cause PPPM total costs were $ 4,421 ( median = $ 2,964 ) compared to $ 3,352 ( median = $ 665 ) p < 0.0001 ) for cases and controls respectively . Multivariate analyses controlling for differences in comorbidities showed mean adjusted PPPM costs to be 2.28 times ( p < 0.0001 ) higher than non-breast cancer controls . Discussion This study demonstrated that breast cancer treatment was associated with substantial healthcare costs , driven mainly by hospitalizations . Projected annual costs for a breast cancer patient would be at least $ 12,828 higher than that for women without breast cancer based upon unadjusted cost differences BACKGROUND Tamoxifen is st and ard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer . We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy . METHODS We undertook a phase 3 , parallel , r and omised trial ( SWOG-8814 , INT-0100 ) in postmenopausal women with hormone-receptor-positive , node-positive breast cancer to test two major objectives : whether the primary outcome , disease-free survival , was longer with cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone ; and whether disease-free survival was longer with CAF followed by tamoxifen ( CAF-T ) than with CAF plus concurrent tamoxifen ( CAFT ) .  Overall survival and toxicity were predefined , important secondary outcomes for each objective . Patients in this open-label trial were r and omly assigned by a computer algorithm in a 2:3:3 ratio ( tamoxifen : CAF-T : CAFT ) and analysis was by intention to treat of eligible patients . Groups were compared by stratified log-rank tests , followed by Cox regression analyses adjusted for significant prognostic factors . This trial is registered with Clinical Trials.gov , number NCT00929591 . FINDINGS Of 1558 r and omised women , 1477 ( 95 % ) were eligible for inclusion in the analysis . After a maximum of 13 years of follow-up ( median 8.94 years ) , 637 women had a disease-free survival event  ( tamoxifen , 179 events in 361 patients ; CAF-T , 216 events in 566 patients ; CAFT , 242 events in 550 patients ) . For the first objective , therapy with the CAF plus tamoxifen groups combined ( CAFT or CAF-T ) was superior to tamoxifen alone for the primary endpoint of disease-free survival ( adjusted Cox regression hazard ratio [ HR ] 0.76 , 95 % CI 0.64 - 0.91 ; p=0.002 ) but only marginally for the secondary endpoint of overall survival ( HR 0.83 , 0.68 - 1.01 ; p=0.057 ) . For the second objective , the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival ( HR 0.84 , 0.70 - 1.01 ; p=0.061 ) or overall survival ( HR 0.90 , 0.73 - 1.10 ; p=0.30 ) . Neutropenia , stomatitis , thromboembolism , congestive heart failure , and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group . INTERPRETATION Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive , node-positive breast cancer than is tamoxifen alone . However , it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes . FUNDING National Cancer Institute ( US National Institutes of Health ) 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 Summary : This prospect i ve longitudinal study examined both short- and long-term changes in health-related quality of life ( HRQL ) in 52 breast cancer patients with poor prognosis receiving high-dose chemotherapy ( HDC ) treatment with autologous blood stem cell transplantation ( ASCT ) .  HRQL was measured seven times from baseline to 2 years post enrollment with the Functional Living Index-Cancer ( FLIC ) , the EuroQol ( EQ-5D ) , and a  quality of life visual analogue scale . The percentage of question naires returned at each assessment time ranged from 80 to 92 % . All three measures showed a similar pattern of change , with HRQL decreasing following administration of HDC , and returning to baseline levels 8 weeks post HDC . A repeated- measures analysis of variance showed that the FLIC at 2 years was significantly better than baseline ( P=<0.0001 ) . Difficulty sleeping , headaches , and decreased sexual interest were the most common symptoms reported in the longer term . Our results have implication s for early psychosocial intervention in the care of breast cancer patients with poor prognosis undergoing treatment with HDC and ASCT because such interventions can further improve the quality of their survival The use of taxanes to treat node-positive ( N+ ) breast cancer patients is associated with heterogeneous benefits as well as with morbidity and financial costs . This study aim ed to assess the economic impact of using gene expression profiling to guide decision-making about chemotherapy , and to discuss the coverage/reimbursement issues involved . Retrospective data on 246 patients included in a r and omised trial ( PACS01 ) were analyzed . Tumours were genotyped using DNA microarrays ( 189-gene signature ) , and patients were classified depending on whether or not they were likely to benefit from chemotherapy regimens without taxanes . St and ard anthracyclines plus taxane chemotherapy ( strategy AT ) was compared with the innovative strategy based on genomic testing ( GEN ) . Statistical analyses involved bootstrap methods and sensitivity analyses . The AT and GEN strategies yielded similar 5-year metastasis-free survival rates . In comparison with AT , GEN was cost-effective when genomic testing costs were less than 2,090€. With genomic testing costs higher than 2,919 € , AT was cost-effective . Considering a 30 % decrease in the price of docetaxel ( the patent rights being about to expire ) , GEN was cost-effective if the cost of genomic testing was in the 0€–1,139 € range ; whereas AT was cost-effective if genomic testing costs were higher than 1,891€. The use of  gene expression profiling  to guide decision-making about chemotherapy for N+ breast cancer patients is potentially cost-effective . Since genomic testing and the drugs targeted in these tests yield greater well-being than the sum of those result ing from separate use , questions arise about how to deal with extra well-being in decision-making about coverage/reimbursement PURPOSE The 21-gene recurrence score ( RS ) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive , lymph node-negative breast cancer treated with adjuvant tamoxifen .  The relationship between the RS and chemotherapy benefit is not known . METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B20 trial . Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS . RESULTS A total of 651 patients were assessable ( 227 r and omly assigned to tamoxifen and 424 r and omly assigned to tamoxifen plus chemotherapy ) . The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038 ) . Patients with high-RS ( > or = 31 ) tumors ( ie , high risk of recurrence ) had a large benefit from  chemotherapy  ( relative risk , 0.26 ; 95 % CI , 0.13 to 0.53 ; absolute decrease in 10-year distant recurrence rate : mean , 27.6 % ; SE , 8.0 % ) . Patients with low-RS ( < 18 ) tumors derived minimal , if any , benefit from chemotherapy treatment ( relative risk , 1.31 ; 95 % CI , 0.46 to 3.78 ; absolute decrease in distant recurrence rate at 10 years : mean , -1.1 % ; SE , 2.2 % ) . Patients with intermediate-RS tumors did not appear to have a large benefit , but the uncertainty in the estimate can not exclude a clinical ly important benefit . CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative , estrogen receptor-positive breast cancer , but also predicts the magnitude of  chemotherapy benefit PURPOSE Adjuvant ! is a st and ardized vali date d decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy . Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features . PATIENTS AND METHODS A sample of 465 patients with hormone receptor ( HR ) -positive breast cancer with zero to three positive axillary nodes who did ( n = 99 ) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay .  Histologic grade and HR expression were evaluated locally and in a central laboratory . RESULTS Recurrence Score ( RS ) was a highly significant predictor of recurrence , including node-negative and node-positive disease ( P < .001 for both ) and when adjusted for other clinical variables . RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant ! that was adjusted to 5-year outcomes . The 5-year recurrence rate was only 5 % or less for the estimated 46 % of patients who have a low RS ( < 18 ) . CONCLUSION The 21-gene assay was a more accurate predictor of relapse than st and ard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy  and provides information that is complementary to features typically used in anatomic staging , 
    Output:
    
Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches .
Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization .
Findings were sensitive to variation in the frequency of chemotherapy prescription , chemotherapy costs , and patients ’ risk profiles .
Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy .