***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 Increased expression of the multidrug resistance gene ( MDR1 ) has been implicated in osteosarcoma prognosis . This study represents the first prospect i ve assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma . PATIENTS AND METHODS A series of patients with high- grade , nonmetastatic extremity osteosarcoma were enrolled from six tertiary care institutions and observed prospect ively for tumor recurrence ( median follow-up duration , 30 months ) . All patients were treated with (neo)adjuvant chemotherapy and surgery .  Tumors from 123 patients were analyzed for MDR1 mRNA expression . The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors . RESULTS Using the highest MDR1 value for each patient , a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse ( relative risk , 1.15 ; P = .44 ) . Analyses based on biopsy or resection values alone gave similar results ( P = .11 and .41 , respectively , log rank test ) . In multivariate analysis , large tumor size ( > 9 cm ) was the only significant independent predictor of systemic outcome ( relative risk , 2.8 ; P = .002 ) . CONCLUSION We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma . It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease PURPOSE A strong prognostic impact of urokinase-type plasminogen activator ( uPA ) and its inhibitor and plasminogen activator inhibitor type 1 ( PAI-1 ) as individual factors is well established in breast cancer . The improvement in clinical risk assessment gained by combining these factors is evaluated here . PATIENTS AND METHODS  uPA and PAI-1 levels  were prospect ively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer . RESULTS In the clinical ly important subgroup of node-negative patients without adjuvant systemic therapy ( n = 269 ; median follow-up , 60 months ) , the clinical value of testing both uPA and PAI-1 is demonstrated . The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group . uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival ; patients with high uPA/PAI-1 have an increased relapse risk ( P < .001 ; relative risk , 4.8 ; 95 % confidence interval [ CI ] , 2.5 to 9.1 ) , in particular for early relapse . Even within risk groups stratified by established criteria ( nodal or menopausal status , tumor size , grade , or steroid hormone receptors ) , uPA/PAI-1 provides significant risk group discrimination . In the whole collective , the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1 . CONCLUSION The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination . The particular combination of uPA and PAI-1 ( both low v either or both high ) is superior to either factor alone and supports risk-adapted individualized therapy decisions 
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A more recently introduced predictive marker is HER-2 for selecting patients with advanced breast cancer for treatment with the therapeutic antibody trastuzumab ( Herceptin ) .
In adjuvant breast cancer , overproduction of HER-2 may also indicate an enhanced sensitivity to high-dose anthracycline-based regimens .
On the other h and , in both early and advanced breast cancer , high concentrations of HER-2 appear to correlate with a lower probability of response to hormone therapy .
Although many different anticancer drugs appear to mediate tumor regression by inducing apoptosis , there is currently no consistent evidence that any of the molecules implicated in this process can be used as predictive markers .
Currently , the only recommended predictive markers in oncology are ER and PR for selecting endocrine-sensitive breast cancers and HER-2 for identifying breast cancer patients with metastatic disease who may benefit from trastuzumab .