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BT 26.250 588.297 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 568.343 Td /F1 9.8 Tf  [(Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after )] TJ ET
BT 26.250 556.438 Td /F1 9.8 Tf  [(treatment. Most women with Stage I or II node-negative breast cancer \(especially when estrogen-receptor positive and treated )] TJ ET
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BT 26.250 520.724 Td /F1 9.8 Tf  [(intended to supplement information used by clinicians and patients in treatment decision-making.)] TJ ET
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BT 26.250 311.484 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 291.530 Td /F1 9.8 Tf  [(Breast cancer is the most commonly diagnosed cancer in U.S. women with an estimated 207,090 new cases in 2010. Among )] TJ ET
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BT 395.297 267.720 Td /F1 9.8 Tf  [( Among women with early stage node-)] TJ ET
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BT 26.250 568.343 Td /F1 9.8 Tf  [(Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after )] TJ ET
BT 26.250 556.438 Td /F1 9.8 Tf  [(treatment. Most women with Stage I or II node-negative breast cancer \(especially when estrogen-receptor positive and treated )] TJ ET
BT 26.250 544.533 Td /F1 9.8 Tf  [(with tamoxifen\) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to )] TJ ET
BT 26.250 532.629 Td /F1 9.8 Tf  [(benefit from chemotherapy. Several clinically available gene expression profiles \(GEP\) provide �recurrence risk scores� that are )] TJ ET
BT 26.250 520.724 Td /F1 9.8 Tf  [(intended to supplement information used by clinicians and patients in treatment decision-making.)] TJ ET
BT 26.250 484.121 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 464.167 Td /F1 9.8 Tf  [(Tumor gene expression profiling in women with Stage I or II node-negative breast cancer to predict recurrence risk and guide )] TJ ET
BT 26.250 452.262 Td /F1 9.8 Tf  [(decisions about chemotherapy.)] TJ ET
BT 26.250 415.660 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 395.706 Td /F1 9.8 Tf  [(Reverse transcription PCR is used by Oncotype DX and the H:I Ratio Test \(Breast cancer Gene Expression Ratio Assay\) for the )] TJ ET
BT 26.250 383.801 Td /F1 9.8 Tf  [(detection and quantification of mRNA in formalin fixed, paraffin-embedded breast cancer tissue. Oncotype DX analyzes the )] TJ ET
BT 26.250 371.896 Td /F1 9.8 Tf  [(expression of 21 genes \(16 cancer related and 5 normative\). The H:I Ratio Test measures the ratio of the expression of the )] TJ ET
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BT 26.250 311.484 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 291.530 Td /F1 9.8 Tf  [(Breast cancer is the most commonly diagnosed cancer in U.S. women with an estimated 207,090 new cases in 2010. Among )] TJ ET
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BT 26.250 267.720 Td /F1 9.8 Tf  [(for over 50% of all diagnoses, and is associated with a 5 year survival rate of 98%. )] TJ ET
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BT 26.250 220.101 Td /F1 9.8 Tf  [(cases, most commonly selection of endocrine therapy alone due to reclassification of women from high to low-risk of recurrence )] TJ ET
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BT 58.776 208.197 Td /F1 9.8 Tf  [( If tumor gene expression profiles are conclusively shown to result in more accurate classification of women into low and )] TJ ET
BT 26.250 196.292 Td /F1 9.8 Tf  [(high recurrence risk categories, theoretical benefits would include avoidance of unnecessary chemotherapy and reduced )] TJ ET
BT 26.250 184.387 Td /F1 9.8 Tf  [(disease recurrence rates.)] TJ ET
BT 26.250 147.785 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 127.830 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
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BT 26.250 588.297 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 568.343 Td /F1 9.8 Tf  [(Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after )] TJ ET
BT 26.250 556.438 Td /F1 9.8 Tf  [(treatment. Most women with Stage I or II node-negative breast cancer \(especially when estrogen-receptor positive and treated )] TJ ET
BT 26.250 544.533 Td /F1 9.8 Tf  [(with tamoxifen\) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to )] TJ ET
BT 26.250 532.629 Td /F1 9.8 Tf  [(benefit from chemotherapy. Several clinically available gene expression profiles \(GEP\) provide �recurrence risk scores� that are )] TJ ET
BT 26.250 520.724 Td /F1 9.8 Tf  [(intended to supplement information used by clinicians and patients in treatment decision-making.)] TJ ET
BT 26.250 484.121 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 464.167 Td /F1 9.8 Tf  [(Tumor gene expression profiling in women with Stage I or II node-negative breast cancer to predict recurrence risk and guide )] TJ ET
BT 26.250 452.262 Td /F1 9.8 Tf  [(decisions about chemotherapy.)] TJ ET
BT 26.250 415.660 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 395.706 Td /F1 9.8 Tf  [(Reverse transcription PCR is used by Oncotype DX and the H:I Ratio Test \(Breast cancer Gene Expression Ratio Assay\) for the )] TJ ET
BT 26.250 383.801 Td /F1 9.8 Tf  [(detection and quantification of mRNA in formalin fixed, paraffin-embedded breast cancer tissue. Oncotype DX analyzes the )] TJ ET
BT 26.250 371.896 Td /F1 9.8 Tf  [(expression of 21 genes \(16 cancer related and 5 normative\). The H:I Ratio Test measures the ratio of the expression of the )] TJ ET
BT 26.250 359.991 Td /F1 9.8 Tf  [(homeobox gene-B13 \(HOXB13\) and the interleukin-17B receptor gene \(IL17BR\). MammaPrint uses micro-array technology to )] TJ ET
BT 26.250 348.087 Td /F1 9.8 Tf  [(test for 70 cancer related and about 1800 normative genes in unfixed \(fresh or frozen\) breast cancer tissue. )] TJ ET
0.267 0.267 0.267 rg
BT 491.228 348.087 Td /F1 9.8 Tf  [([1])] TJ ET
BT 502.070 348.087 Td /F1 9.8 Tf  [([2])] TJ ET
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BT 26.250 311.484 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 291.530 Td /F1 9.8 Tf  [(Breast cancer is the most commonly diagnosed cancer in U.S. women with an estimated 207,090 new cases in 2010. Among )] TJ ET
BT 26.250 279.625 Td /F1 9.8 Tf  [(U.S. women, it is the second leading cause of cancer-related deaths \(estimated 39,840 deaths in 2010\). )] TJ ET
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BT 476.603 279.625 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 487.445 279.625 Td /F1 9.8 Tf  [( Stage I/II accounts )] TJ ET
BT 26.250 267.720 Td /F1 9.8 Tf  [(for over 50% of all diagnoses, and is associated with a 5 year survival rate of 98%. )] TJ ET
0.267 0.267 0.267 rg
BT 384.455 267.720 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 395.297 267.720 Td /F1 9.8 Tf  [( Among women with early stage node-)] TJ ET
BT 26.250 255.816 Td /F1 9.8 Tf  [(negative disease, the majority elect to receive chemotherapy on the basis of standard recurrence risk classification using tumor )] TJ ET
BT 26.250 243.911 Td /F1 9.8 Tf  [(characteristics. )] TJ ET
0.267 0.267 0.267 rg
BT 93.974 243.911 Td /F1 9.8 Tf  [([5])] TJ ET
BT 104.816 243.911 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 115.657 243.911 Td /F1 9.8 Tf  [( Approximately 60%, 5%, and 0.5% of women respectively will experience minor, major or fatal toxicity from )] TJ ET
BT 26.250 232.006 Td /F1 9.8 Tf  [(chemotherapy. )] TJ ET
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BT 93.447 232.006 Td /F1 9.8 Tf  [([7])] TJ ET
BT 104.289 232.006 Td /F1 9.8 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 115.131 232.006 Td /F1 9.8 Tf  [( Studies of use of breast cancer GEP suggest changes in treatment decisions in approximately 25-30% of )] TJ ET
BT 26.250 220.101 Td /F1 9.8 Tf  [(cases, most commonly selection of endocrine therapy alone due to reclassification of women from high to low-risk of recurrence )] TJ ET
BT 26.250 208.197 Td /F1 9.8 Tf  [(. )] TJ ET
0.267 0.267 0.267 rg
BT 31.671 208.197 Td /F1 9.8 Tf  [([9])] TJ ET
BT 42.513 208.197 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 58.776 208.197 Td /F1 9.8 Tf  [( If tumor gene expression profiles are conclusively shown to result in more accurate classification of women into low and )] TJ ET
BT 26.250 196.292 Td /F1 9.8 Tf  [(high recurrence risk categories, theoretical benefits would include avoidance of unnecessary chemotherapy and reduced )] TJ ET
BT 26.250 184.387 Td /F1 9.8 Tf  [(disease recurrence rates.)] TJ ET
BT 26.250 147.785 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 127.830 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 108.426 Td /F1 9.8 Tf  [(Agency for Healthcare Research and Quality, Evidence Report/Technology Assessment )] TJ ET
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BT 26.250 767.476 Td /F1 9.8 Tf  [(recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with breast cancer.� )] TJ ET
0.267 0.267 0.267 rg
BT 114.029 755.571 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 736.167 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
0.271 0.267 0.267 RG
40.337 719.730 m 
40.337 720.176 40.154 720.620 39.838 720.936 c
39.522 721.252 39.078 721.436 38.631 721.436 c
38.185 721.436 37.741 721.252 37.425 720.936 c
37.109 720.620 36.925 720.176 36.925 719.730 c
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39.078 718.023 39.522 718.207 39.838 718.523 c
40.154 718.839 40.337 719.283 40.337 719.730 c f
BT 45.750 716.762 Td /F1 9.8 Tf  [(National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology � Breast Cancer )] TJ ET
0.267 0.267 0.267 rg
BT 478.679 716.762 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 494.942 716.762 Td /F1 9.8 Tf  [( American Society )] TJ ET
BT 45.750 704.857 Td /F1 9.8 Tf  [(of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 487.932 704.857 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 504.195 704.857 Td /F1 9.8 Tf  [( ECRI Institute: )] TJ ET
BT 45.750 692.952 Td /F1 9.8 Tf  [(Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 121.615 692.952 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 680.265 m 
40.337 680.712 40.154 681.156 39.838 681.472 c
39.522 681.788 39.078 681.971 38.631 681.971 c
38.185 681.971 37.741 681.788 37.425 681.472 c
37.109 681.156 36.925 680.712 36.925 680.265 c
36.925 679.819 37.109 679.375 37.425 679.059 c
37.741 678.743 38.185 678.559 38.631 678.559 c
39.078 678.559 39.522 678.743 39.838 679.059 c
40.154 679.375 40.337 679.819 40.337 680.265 c f
BT 45.750 677.298 Td /F1 9.8 Tf  [(American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 45.750 665.393 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
40.337 652.706 m 
40.337 653.152 40.154 653.596 39.838 653.912 c
39.522 654.228 39.078 654.412 38.631 654.412 c
38.185 654.412 37.741 654.228 37.425 653.912 c
37.109 653.596 36.925 653.152 36.925 652.706 c
36.925 652.259 37.109 651.815 37.425 651.499 c
37.741 651.183 38.185 651.000 38.631 651.000 c
39.078 651.000 39.522 651.183 39.838 651.499 c
40.154 651.815 40.337 652.259 40.337 652.706 c f
BT 45.750 649.738 Td /F1 9.8 Tf  [(ECRI Institute: Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 187.184 649.738 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.583 Td /F5 9.8 Tf  [(* independent groups include the US Preventive Services Task Force \(USPSTF\) and Evaluation of Genomic Applications in )] TJ ET
BT 26.250 614.679 Td /F5 9.8 Tf  [(Practice and Prevention \(EGAPP\) Working Group.)] TJ ET
BT 26.250 578.076 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 558.122 Td /F6 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 558.122 Td /F4 9.8 Tf  [( : )] TJ ET
BT 110.236 558.122 Td /F1 9.8 Tf  [(Test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 546.217 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
40.337 529.780 m 
40.337 530.227 40.154 530.671 39.838 530.987 c
39.522 531.302 39.078 531.486 38.631 531.486 c
38.185 531.486 37.741 531.302 37.425 530.987 c
37.109 530.671 36.925 530.227 36.925 529.780 c
36.925 529.333 37.109 528.889 37.425 528.573 c
37.741 528.258 38.185 528.074 38.631 528.074 c
39.078 528.074 39.522 528.258 39.838 528.573 c
40.154 528.889 40.337 529.333 40.337 529.780 c f
BT 45.750 526.812 Td /F1 9.8 Tf  [(A 2009 EGAPP Working Group recommendation statement )] TJ ET
0.267 0.267 0.267 rg
BT 304.778 526.812 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 315.620 526.812 Td /F1 9.8 Tf  [(suggested that: )] TJ ET
0.39 w 1 J 1 j
59.837 514.125 m 
59.837 514.572 59.654 515.016 59.338 515.332 c
59.022 515.648 58.578 515.831 58.131 515.831 c
57.685 515.831 57.241 515.648 56.925 515.332 c
56.609 515.016 56.425 514.572 56.425 514.125 c
56.425 513.679 56.609 513.235 56.925 512.919 c
57.241 512.603 57.685 512.419 58.131 512.419 c
58.578 512.419 59.022 512.603 59.338 512.919 c
59.654 513.235 59.837 513.679 59.837 514.125 c s
BT 65.250 511.158 Td /F1 9.8 Tf  [(limited published data are available regarding assay performance of clinically available GEP,)] TJ ET
0.39 w 1 J 1 j
59.837 498.470 m 
59.837 498.917 59.654 499.361 59.338 499.677 c
59.022 499.993 58.578 500.177 58.131 500.177 c
57.685 500.177 57.241 499.993 56.925 499.677 c
56.609 499.361 56.425 498.917 56.425 498.470 c
56.425 498.024 56.609 497.580 56.925 497.264 c
57.241 496.948 57.685 496.764 58.131 496.764 c
58.578 496.764 59.022 496.948 59.338 497.264 c
59.654 497.580 59.837 498.024 59.837 498.470 c s
BT 65.250 495.503 Td /F1 9.8 Tf  [(analytic sensitivity and specificity cannot be estimated because no reference technology \(�gold standard�\) is available )] TJ ET
BT 65.250 483.598 Td /F1 9.8 Tf  [(for comparison,)] TJ ET
0.39 w 1 J 1 j
59.837 470.911 m 
59.837 471.358 59.654 471.802 59.338 472.118 c
59.022 472.433 58.578 472.617 58.131 472.617 c
57.685 472.617 57.241 472.433 56.925 472.118 c
56.609 471.802 56.425 471.358 56.425 470.911 c
56.425 470.464 56.609 470.020 56.925 469.704 c
57.241 469.389 57.685 469.205 58.131 469.205 c
58.578 469.205 59.022 469.389 59.338 469.704 c
59.654 470.020 59.837 470.464 59.837 470.911 c s
BT 65.250 467.943 Td /F1 9.8 Tf  [(initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.)] TJ ET
40.337 451.506 m 
40.337 451.953 40.154 452.397 39.838 452.713 c
39.522 453.029 39.078 453.213 38.631 453.213 c
38.185 453.213 37.741 453.029 37.425 452.713 c
37.109 452.397 36.925 451.953 36.925 451.506 c
36.925 451.060 37.109 450.616 37.425 450.300 c
37.741 449.984 38.185 449.800 38.631 449.800 c
39.078 449.800 39.522 449.984 39.838 450.300 c
40.154 450.616 40.337 451.060 40.337 451.506 c f
BT 45.750 448.539 Td /F1 9.8 Tf  [(One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available. )] TJ ET
0.267 0.267 0.267 rg
BT 515.047 448.539 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
40.337 435.852 m 
40.337 436.298 40.154 436.742 39.838 437.058 c
39.522 437.374 39.078 437.558 38.631 437.558 c
38.185 437.558 37.741 437.374 37.425 437.058 c
37.109 436.742 36.925 436.298 36.925 435.852 c
36.925 435.405 37.109 434.961 37.425 434.645 c
37.741 434.329 38.185 434.145 38.631 434.145 c
39.078 434.145 39.522 434.329 39.838 434.645 c
40.154 434.961 40.337 435.405 40.337 435.852 c f
BT 45.750 432.884 Td /F1 9.8 Tf  [(he FDA summary of MammaPrint provided information on result and classification accuracy )] TJ ET
0.267 0.267 0.267 rg
BT 442.916 432.884 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 409.729 Td /F6 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 409.729 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 409.729 Td /F1 9.8 Tf  [( Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy )] TJ ET
BT 26.250 397.824 Td /F1 9.8 Tf  [(\(predictive value\).)] TJ ET
40.337 381.387 m 
40.337 381.834 40.154 382.278 39.838 382.594 c
39.522 382.910 39.078 383.094 38.631 383.094 c
38.185 383.094 37.741 382.910 37.425 382.594 c
37.109 382.278 36.925 381.834 36.925 381.387 c
36.925 380.941 37.109 380.497 37.425 380.181 c
37.741 379.865 38.185 379.681 38.631 379.681 c
39.078 379.681 39.522 379.865 39.838 380.181 c
40.154 380.497 40.337 380.941 40.337 381.387 c f
BT 45.750 378.420 Td /F1 9.8 Tf  [(Several studies have reported on the clinical validity for Oncotype DX.)] TJ ET
0.267 0.267 0.267 rg
BT 347.045 378.420 Td /F1 9.8 Tf  [([17])] TJ ET
BT 363.308 378.420 Td /F1 9.8 Tf  [([18])] TJ ET
BT 379.570 378.420 Td /F1 9.8 Tf  [([19])] TJ ET
BT 395.833 378.420 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 365.733 m 
40.337 366.179 40.154 366.623 39.838 366.939 c
39.522 367.255 39.078 367.439 38.631 367.439 c
38.185 367.439 37.741 367.255 37.425 366.939 c
37.109 366.623 36.925 366.179 36.925 365.733 c
36.925 365.286 37.109 364.842 37.425 364.526 c
37.741 364.210 38.185 364.026 38.631 364.026 c
39.078 364.026 39.522 364.210 39.838 364.526 c
40.154 364.842 40.337 365.286 40.337 365.733 c f
BT 45.750 362.765 Td /F1 9.8 Tf  [(A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence )] TJ ET
BT 45.750 350.860 Td /F1 9.8 Tf  [(using data from the NSABP B-14 and B-20 trials.)] TJ ET
0.267 0.267 0.267 rg
BT 256.555 350.860 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
40.337 338.173 m 
40.337 338.620 40.154 339.064 39.838 339.380 c
39.522 339.695 39.078 339.879 38.631 339.879 c
38.185 339.879 37.741 339.695 37.425 339.380 c
37.109 339.064 36.925 338.620 36.925 338.173 c
36.925 337.726 37.109 337.282 37.425 336.966 c
37.741 336.651 38.185 336.467 38.631 336.467 c
39.078 336.467 39.522 336.651 39.838 336.966 c
40.154 337.282 40.337 337.726 40.337 338.173 c f
BT 45.750 335.205 Td /F1 9.8 Tf  [(Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index \(high )] TJ ET
BT 45.750 323.301 Td /F1 9.8 Tf  [(vs. low risk\) and 5 and 10 year distant recurrence rates.)] TJ ET
0.267 0.267 0.267 rg
BT 285.805 323.301 Td /F1 9.8 Tf  [([22])] TJ ET
BT 302.068 323.301 Td /F1 9.8 Tf  [([23])] TJ ET
BT 318.331 323.301 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 334.594 323.301 Td /F1 9.8 Tf  [(However: )] TJ ET
0.39 w 1 J 1 j
59.837 310.614 m 
59.837 311.060 59.654 311.504 59.338 311.820 c
59.022 312.136 58.578 312.320 58.131 312.320 c
57.685 312.320 57.241 312.136 56.925 311.820 c
56.609 311.504 56.425 311.060 56.425 310.614 c
56.425 310.167 56.609 309.723 56.925 309.407 c
57.241 309.091 57.685 308.907 58.131 308.907 c
58.578 308.907 59.022 309.091 59.338 309.407 c
59.654 309.723 59.837 310.167 59.837 310.614 c s
BT 65.250 307.646 Td /F1 9.8 Tf  [(efficacy in ER positive vs. negative cases is unclear,)] TJ ET
0.267 0.267 0.267 rg
BT 290.670 307.646 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
0.39 w 1 J 1 j
59.837 294.959 m 
59.837 295.405 59.654 295.849 59.338 296.165 c
59.022 296.481 58.578 296.665 58.131 296.665 c
57.685 296.665 57.241 296.481 56.925 296.165 c
56.609 295.849 56.425 295.405 56.425 294.959 c
56.425 294.512 56.609 294.068 56.925 293.752 c
57.241 293.436 57.685 293.253 58.131 293.253 c
58.578 293.253 59.022 293.436 59.338 293.752 c
59.654 294.068 59.837 294.512 59.837 294.959 c s
BT 65.250 291.991 Td /F1 9.8 Tf  [(added value beyond standard risk stratification is unclear.)] TJ ET
0.267 0.267 0.267 rg
BT 313.446 291.991 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 275.554 m 
40.337 276.001 40.154 276.445 39.838 276.761 c
39.522 277.076 39.078 277.260 38.631 277.260 c
38.185 277.260 37.741 277.076 37.425 276.761 c
37.109 276.445 36.925 276.001 36.925 275.554 c
36.925 275.107 37.109 274.663 37.425 274.347 c
37.741 274.032 38.185 273.848 38.631 273.848 c
39.078 273.848 39.522 274.032 39.838 274.347 c
40.154 274.663 40.337 275.107 40.337 275.554 c f
BT 45.750 272.586 Td /F1 9.8 Tf  [(A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to )] TJ ET
BT 45.750 260.682 Td /F1 9.8 Tf  [(Oncotype DX, Mammaprint and the H:I Ratio Test.)] TJ ET
40.337 247.995 m 
40.337 248.441 40.154 248.885 39.838 249.201 c
39.522 249.517 39.078 249.701 38.631 249.701 c
38.185 249.701 37.741 249.517 37.425 249.201 c
37.109 248.885 36.925 248.441 36.925 247.995 c
36.925 247.548 37.109 247.104 37.425 246.788 c
37.741 246.472 38.185 246.288 38.631 246.288 c
39.078 246.288 39.522 246.472 39.838 246.788 c
40.154 247.104 40.337 247.548 40.337 247.995 c f
BT 45.750 245.027 Td /F1 9.8 Tf  [(All were significantly associated with time to progression; however, concordance of results among the three classifiers was )] TJ ET
BT 45.750 233.122 Td /F1 9.8 Tf  [(relatively low, classifying only 45-61% of patients in the same category.)] TJ ET
0.267 0.267 0.267 rg
BT 352.456 233.122 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 209.967 Td /F4 9.8 Tf  [(Clinical Utility: )] TJ ET
BT 96.684 209.967 Td /F1 9.8 Tf  [(Net benefit of test in improving health outcomes.)] TJ ET
40.337 193.530 m 
40.337 193.977 40.154 194.421 39.838 194.737 c
39.522 195.053 39.078 195.237 38.631 195.237 c
38.185 195.237 37.741 195.053 37.425 194.737 c
37.109 194.421 36.925 193.977 36.925 193.530 c
36.925 193.084 37.109 192.640 37.425 192.324 c
37.741 192.008 38.185 191.824 38.631 191.824 c
39.078 191.824 39.522 192.008 39.838 192.324 c
40.154 192.640 40.337 193.084 40.337 193.530 c f
BT 45.750 190.563 Td /F1 9.8 Tf  [(Retrospective analysis of one arm of a single prospective trial \(NSABP B-20\) showed that chemotherapy \(in addition to )] TJ ET
BT 45.750 178.658 Td /F1 9.8 Tf  [(tamoxifen\) was most beneficial in women in the Oncotype DX high risk category.)] TJ ET
0.267 0.267 0.267 rg
BT 392.548 178.658 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 165.971 m 
40.337 166.417 40.154 166.861 39.838 167.177 c
39.522 167.493 39.078 167.677 38.631 167.677 c
38.185 167.677 37.741 167.493 37.425 167.177 c
37.109 166.861 36.925 166.417 36.925 165.971 c
36.925 165.524 37.109 165.080 37.425 164.764 c
37.741 164.448 38.185 164.265 38.631 164.265 c
39.078 164.265 39.522 164.448 39.838 164.764 c
40.154 165.080 40.337 165.524 40.337 165.971 c f
BT 45.750 163.003 Td /F1 9.8 Tf  [(A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician )] TJ ET
BT 45.750 151.098 Td /F1 9.8 Tf  [(adjuvant chemotherapy decisions.)] TJ ET
0.267 0.267 0.267 rg
BT 193.150 151.098 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
40.337 138.411 m 
40.337 138.858 40.154 139.302 39.838 139.618 c
39.522 139.934 39.078 140.118 38.631 140.118 c
38.185 140.118 37.741 139.934 37.425 139.618 c
37.109 139.302 36.925 138.858 36.925 138.411 c
36.925 137.965 37.109 137.521 37.425 137.205 c
37.741 136.889 38.185 136.705 38.631 136.705 c
39.078 136.705 39.522 136.889 39.838 137.205 c
40.154 137.521 40.337 137.965 40.337 138.411 c f
BT 45.750 135.444 Td /F1 9.8 Tf  [(Analyses of economic implications of Oncotype DX have been published. )] TJ ET
0.267 0.267 0.267 rg
BT 363.853 135.444 Td /F1 9.8 Tf  [([5])] TJ ET
BT 374.695 135.444 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
40.337 122.757 m 
40.337 123.203 40.154 123.647 39.838 123.963 c
39.522 124.279 39.078 124.463 38.631 124.463 c
38.185 124.463 37.741 124.279 37.425 123.963 c
37.109 123.647 36.925 123.203 36.925 122.757 c
36.925 122.310 37.109 121.866 37.425 121.550 c
37.741 121.234 38.185 121.050 38.631 121.050 c
39.078 121.050 39.522 121.234 39.838 121.550 c
40.154 121.866 40.337 122.310 40.337 122.757 c f
BT 45.750 119.789 Td /F1 9.8 Tf  [(2010 publication explored women�s experiences with genomic testing for breast cancer recurrence risk in terms of how )] TJ ET
BT 45.750 107.884 Td /F1 9.8 Tf  [(scores were received and understood.)] TJ ET
0.267 0.267 0.267 rg
BT 211.032 107.884 Td /F1 9.8 Tf  [([27])] TJ ET
0.271 0.267 0.267 rg
40.337 95.197 m 
40.337 95.644 40.154 96.088 39.838 96.404 c
39.522 96.719 39.078 96.903 38.631 96.903 c
38.185 96.903 37.741 96.719 37.425 96.404 c
37.109 96.088 36.925 95.644 36.925 95.197 c
36.925 94.750 37.109 94.306 37.425 93.990 c
37.741 93.675 38.185 93.491 38.631 93.491 c
39.078 93.491 39.522 93.675 39.838 93.990 c
40.154 94.306 40.337 94.750 40.337 95.197 c f
BT 45.750 92.229 Td /F1 9.8 Tf  [(A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical )] TJ ET
BT 45.750 80.325 Td /F1 9.8 Tf  [(outcomes.)] TJ ET
0.267 0.267 0.267 rg
BT 90.727 80.325 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 67.638 m 
40.337 68.084 40.154 68.528 39.838 68.844 c
39.522 69.160 39.078 69.344 38.631 69.344 c
38.185 69.344 37.741 69.160 37.425 68.844 c
37.109 68.528 36.925 68.084 36.925 67.638 c
36.925 67.191 37.109 66.747 37.425 66.431 c
37.741 66.115 38.185 65.931 38.631 65.931 c
39.078 65.931 39.522 66.115 39.838 66.431 c
40.154 66.747 40.337 67.191 40.337 67.638 c f
BT 45.750 64.670 Td /F1 9.8 Tf  [(Ongoing trials include: )] TJ ET
0.39 w 1 J 1 j
59.837 51.983 m 
59.837 52.429 59.654 52.873 59.338 53.189 c
59.022 53.505 58.578 53.689 58.131 53.689 c
57.685 53.689 57.241 53.505 56.925 53.189 c
56.609 52.873 56.425 52.429 56.425 51.983 c
56.425 51.536 56.609 51.092 56.925 50.776 c
57.241 50.460 57.685 50.277 58.131 50.277 c
58.578 50.277 59.022 50.460 59.338 50.776 c
59.654 51.092 59.837 51.536 59.837 51.983 c s
BT 65.250 49.015 Td /F1 9.8 Tf  [(TAILORx trial \(Oncotype DX\))] TJ ET
0.267 0.267 0.267 rg
BT 190.947 49.015 Td /F1 9.8 Tf  [([28])] TJ ET
Q
q
15.000 42.884 577.500 734.116 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with breast cancer.� )] TJ ET
0.267 0.267 0.267 rg
BT 114.029 755.571 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 736.167 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
0.271 0.267 0.267 RG
40.337 719.730 m 
40.337 720.176 40.154 720.620 39.838 720.936 c
39.522 721.252 39.078 721.436 38.631 721.436 c
38.185 721.436 37.741 721.252 37.425 720.936 c
37.109 720.620 36.925 720.176 36.925 719.730 c
36.925 719.283 37.109 718.839 37.425 718.523 c
37.741 718.207 38.185 718.023 38.631 718.023 c
39.078 718.023 39.522 718.207 39.838 718.523 c
40.154 718.839 40.337 719.283 40.337 719.730 c f
BT 45.750 716.762 Td /F1 9.8 Tf  [(National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology � Breast Cancer )] TJ ET
0.267 0.267 0.267 rg
BT 478.679 716.762 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 494.942 716.762 Td /F1 9.8 Tf  [( American Society )] TJ ET
BT 45.750 704.857 Td /F1 9.8 Tf  [(of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 487.932 704.857 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 504.195 704.857 Td /F1 9.8 Tf  [( ECRI Institute: )] TJ ET
BT 45.750 692.952 Td /F1 9.8 Tf  [(Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 121.615 692.952 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 680.265 m 
40.337 680.712 40.154 681.156 39.838 681.472 c
39.522 681.788 39.078 681.971 38.631 681.971 c
38.185 681.971 37.741 681.788 37.425 681.472 c
37.109 681.156 36.925 680.712 36.925 680.265 c
36.925 679.819 37.109 679.375 37.425 679.059 c
37.741 678.743 38.185 678.559 38.631 678.559 c
39.078 678.559 39.522 678.743 39.838 679.059 c
40.154 679.375 40.337 679.819 40.337 680.265 c f
BT 45.750 677.298 Td /F1 9.8 Tf  [(American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 45.750 665.393 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
40.337 652.706 m 
40.337 653.152 40.154 653.596 39.838 653.912 c
39.522 654.228 39.078 654.412 38.631 654.412 c
38.185 654.412 37.741 654.228 37.425 653.912 c
37.109 653.596 36.925 653.152 36.925 652.706 c
36.925 652.259 37.109 651.815 37.425 651.499 c
37.741 651.183 38.185 651.000 38.631 651.000 c
39.078 651.000 39.522 651.183 39.838 651.499 c
40.154 651.815 40.337 652.259 40.337 652.706 c f
BT 45.750 649.738 Td /F1 9.8 Tf  [(ECRI Institute: Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 187.184 649.738 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.583 Td /F5 9.8 Tf  [(* independent groups include the US Preventive Services Task Force \(USPSTF\) and Evaluation of Genomic Applications in )] TJ ET
BT 26.250 614.679 Td /F5 9.8 Tf  [(Practice and Prevention \(EGAPP\) Working Group.)] TJ ET
BT 26.250 578.076 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 558.122 Td /F6 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 558.122 Td /F4 9.8 Tf  [( : )] TJ ET
BT 110.236 558.122 Td /F1 9.8 Tf  [(Test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 546.217 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
40.337 529.780 m 
40.337 530.227 40.154 530.671 39.838 530.987 c
39.522 531.302 39.078 531.486 38.631 531.486 c
38.185 531.486 37.741 531.302 37.425 530.987 c
37.109 530.671 36.925 530.227 36.925 529.780 c
36.925 529.333 37.109 528.889 37.425 528.573 c
37.741 528.258 38.185 528.074 38.631 528.074 c
39.078 528.074 39.522 528.258 39.838 528.573 c
40.154 528.889 40.337 529.333 40.337 529.780 c f
BT 45.750 526.812 Td /F1 9.8 Tf  [(A 2009 EGAPP Working Group recommendation statement )] TJ ET
0.267 0.267 0.267 rg
BT 304.778 526.812 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 315.620 526.812 Td /F1 9.8 Tf  [(suggested that: )] TJ ET
0.39 w 1 J 1 j
59.837 514.125 m 
59.837 514.572 59.654 515.016 59.338 515.332 c
59.022 515.648 58.578 515.831 58.131 515.831 c
57.685 515.831 57.241 515.648 56.925 515.332 c
56.609 515.016 56.425 514.572 56.425 514.125 c
56.425 513.679 56.609 513.235 56.925 512.919 c
57.241 512.603 57.685 512.419 58.131 512.419 c
58.578 512.419 59.022 512.603 59.338 512.919 c
59.654 513.235 59.837 513.679 59.837 514.125 c s
BT 65.250 511.158 Td /F1 9.8 Tf  [(limited published data are available regarding assay performance of clinically available GEP,)] TJ ET
0.39 w 1 J 1 j
59.837 498.470 m 
59.837 498.917 59.654 499.361 59.338 499.677 c
59.022 499.993 58.578 500.177 58.131 500.177 c
57.685 500.177 57.241 499.993 56.925 499.677 c
56.609 499.361 56.425 498.917 56.425 498.470 c
56.425 498.024 56.609 497.580 56.925 497.264 c
57.241 496.948 57.685 496.764 58.131 496.764 c
58.578 496.764 59.022 496.948 59.338 497.264 c
59.654 497.580 59.837 498.024 59.837 498.470 c s
BT 65.250 495.503 Td /F1 9.8 Tf  [(analytic sensitivity and specificity cannot be estimated because no reference technology \(�gold standard�\) is available )] TJ ET
BT 65.250 483.598 Td /F1 9.8 Tf  [(for comparison,)] TJ ET
0.39 w 1 J 1 j
59.837 470.911 m 
59.837 471.358 59.654 471.802 59.338 472.118 c
59.022 472.433 58.578 472.617 58.131 472.617 c
57.685 472.617 57.241 472.433 56.925 472.118 c
56.609 471.802 56.425 471.358 56.425 470.911 c
56.425 470.464 56.609 470.020 56.925 469.704 c
57.241 469.389 57.685 469.205 58.131 469.205 c
58.578 469.205 59.022 469.389 59.338 469.704 c
59.654 470.020 59.837 470.464 59.837 470.911 c s
BT 65.250 467.943 Td /F1 9.8 Tf  [(initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.)] TJ ET
40.337 451.506 m 
40.337 451.953 40.154 452.397 39.838 452.713 c
39.522 453.029 39.078 453.213 38.631 453.213 c
38.185 453.213 37.741 453.029 37.425 452.713 c
37.109 452.397 36.925 451.953 36.925 451.506 c
36.925 451.060 37.109 450.616 37.425 450.300 c
37.741 449.984 38.185 449.800 38.631 449.800 c
39.078 449.800 39.522 449.984 39.838 450.300 c
40.154 450.616 40.337 451.060 40.337 451.506 c f
BT 45.750 448.539 Td /F1 9.8 Tf  [(One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available. )] TJ ET
0.267 0.267 0.267 rg
BT 515.047 448.539 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
40.337 435.852 m 
40.337 436.298 40.154 436.742 39.838 437.058 c
39.522 437.374 39.078 437.558 38.631 437.558 c
38.185 437.558 37.741 437.374 37.425 437.058 c
37.109 436.742 36.925 436.298 36.925 435.852 c
36.925 435.405 37.109 434.961 37.425 434.645 c
37.741 434.329 38.185 434.145 38.631 434.145 c
39.078 434.145 39.522 434.329 39.838 434.645 c
40.154 434.961 40.337 435.405 40.337 435.852 c f
BT 45.750 432.884 Td /F1 9.8 Tf  [(he FDA summary of MammaPrint provided information on result and classification accuracy )] TJ ET
0.267 0.267 0.267 rg
BT 442.916 432.884 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 409.729 Td /F6 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 409.729 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 409.729 Td /F1 9.8 Tf  [( Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy )] TJ ET
BT 26.250 397.824 Td /F1 9.8 Tf  [(\(predictive value\).)] TJ ET
40.337 381.387 m 
40.337 381.834 40.154 382.278 39.838 382.594 c
39.522 382.910 39.078 383.094 38.631 383.094 c
38.185 383.094 37.741 382.910 37.425 382.594 c
37.109 382.278 36.925 381.834 36.925 381.387 c
36.925 380.941 37.109 380.497 37.425 380.181 c
37.741 379.865 38.185 379.681 38.631 379.681 c
39.078 379.681 39.522 379.865 39.838 380.181 c
40.154 380.497 40.337 380.941 40.337 381.387 c f
BT 45.750 378.420 Td /F1 9.8 Tf  [(Several studies have reported on the clinical validity for Oncotype DX.)] TJ ET
0.267 0.267 0.267 rg
BT 347.045 378.420 Td /F1 9.8 Tf  [([17])] TJ ET
BT 363.308 378.420 Td /F1 9.8 Tf  [([18])] TJ ET
BT 379.570 378.420 Td /F1 9.8 Tf  [([19])] TJ ET
BT 395.833 378.420 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 365.733 m 
40.337 366.179 40.154 366.623 39.838 366.939 c
39.522 367.255 39.078 367.439 38.631 367.439 c
38.185 367.439 37.741 367.255 37.425 366.939 c
37.109 366.623 36.925 366.179 36.925 365.733 c
36.925 365.286 37.109 364.842 37.425 364.526 c
37.741 364.210 38.185 364.026 38.631 364.026 c
39.078 364.026 39.522 364.210 39.838 364.526 c
40.154 364.842 40.337 365.286 40.337 365.733 c f
BT 45.750 362.765 Td /F1 9.8 Tf  [(A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence )] TJ ET
BT 45.750 350.860 Td /F1 9.8 Tf  [(using data from the NSABP B-14 and B-20 trials.)] TJ ET
0.267 0.267 0.267 rg
BT 256.555 350.860 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
40.337 338.173 m 
40.337 338.620 40.154 339.064 39.838 339.380 c
39.522 339.695 39.078 339.879 38.631 339.879 c
38.185 339.879 37.741 339.695 37.425 339.380 c
37.109 339.064 36.925 338.620 36.925 338.173 c
36.925 337.726 37.109 337.282 37.425 336.966 c
37.741 336.651 38.185 336.467 38.631 336.467 c
39.078 336.467 39.522 336.651 39.838 336.966 c
40.154 337.282 40.337 337.726 40.337 338.173 c f
BT 45.750 335.205 Td /F1 9.8 Tf  [(Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index \(high )] TJ ET
BT 45.750 323.301 Td /F1 9.8 Tf  [(vs. low risk\) and 5 and 10 year distant recurrence rates.)] TJ ET
0.267 0.267 0.267 rg
BT 285.805 323.301 Td /F1 9.8 Tf  [([22])] TJ ET
BT 302.068 323.301 Td /F1 9.8 Tf  [([23])] TJ ET
BT 318.331 323.301 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 334.594 323.301 Td /F1 9.8 Tf  [(However: )] TJ ET
0.39 w 1 J 1 j
59.837 310.614 m 
59.837 311.060 59.654 311.504 59.338 311.820 c
59.022 312.136 58.578 312.320 58.131 312.320 c
57.685 312.320 57.241 312.136 56.925 311.820 c
56.609 311.504 56.425 311.060 56.425 310.614 c
56.425 310.167 56.609 309.723 56.925 309.407 c
57.241 309.091 57.685 308.907 58.131 308.907 c
58.578 308.907 59.022 309.091 59.338 309.407 c
59.654 309.723 59.837 310.167 59.837 310.614 c s
BT 65.250 307.646 Td /F1 9.8 Tf  [(efficacy in ER positive vs. negative cases is unclear,)] TJ ET
0.267 0.267 0.267 rg
BT 290.670 307.646 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
0.39 w 1 J 1 j
59.837 294.959 m 
59.837 295.405 59.654 295.849 59.338 296.165 c
59.022 296.481 58.578 296.665 58.131 296.665 c
57.685 296.665 57.241 296.481 56.925 296.165 c
56.609 295.849 56.425 295.405 56.425 294.959 c
56.425 294.512 56.609 294.068 56.925 293.752 c
57.241 293.436 57.685 293.253 58.131 293.253 c
58.578 293.253 59.022 293.436 59.338 293.752 c
59.654 294.068 59.837 294.512 59.837 294.959 c s
BT 65.250 291.991 Td /F1 9.8 Tf  [(added value beyond standard risk stratification is unclear.)] TJ ET
0.267 0.267 0.267 rg
BT 313.446 291.991 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 275.554 m 
40.337 276.001 40.154 276.445 39.838 276.761 c
39.522 277.076 39.078 277.260 38.631 277.260 c
38.185 277.260 37.741 277.076 37.425 276.761 c
37.109 276.445 36.925 276.001 36.925 275.554 c
36.925 275.107 37.109 274.663 37.425 274.347 c
37.741 274.032 38.185 273.848 38.631 273.848 c
39.078 273.848 39.522 274.032 39.838 274.347 c
40.154 274.663 40.337 275.107 40.337 275.554 c f
BT 45.750 272.586 Td /F1 9.8 Tf  [(A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to )] TJ ET
BT 45.750 260.682 Td /F1 9.8 Tf  [(Oncotype DX, Mammaprint and the H:I Ratio Test.)] TJ ET
40.337 247.995 m 
40.337 248.441 40.154 248.885 39.838 249.201 c
39.522 249.517 39.078 249.701 38.631 249.701 c
38.185 249.701 37.741 249.517 37.425 249.201 c
37.109 248.885 36.925 248.441 36.925 247.995 c
36.925 247.548 37.109 247.104 37.425 246.788 c
37.741 246.472 38.185 246.288 38.631 246.288 c
39.078 246.288 39.522 246.472 39.838 246.788 c
40.154 247.104 40.337 247.548 40.337 247.995 c f
BT 45.750 245.027 Td /F1 9.8 Tf  [(All were significantly associated with time to progression; however, concordance of results among the three classifiers was )] TJ ET
BT 45.750 233.122 Td /F1 9.8 Tf  [(relatively low, classifying only 45-61% of patients in the same category.)] TJ ET
0.267 0.267 0.267 rg
BT 352.456 233.122 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 209.967 Td /F4 9.8 Tf  [(Clinical Utility: )] TJ ET
BT 96.684 209.967 Td /F1 9.8 Tf  [(Net benefit of test in improving health outcomes.)] TJ ET
40.337 193.530 m 
40.337 193.977 40.154 194.421 39.838 194.737 c
39.522 195.053 39.078 195.237 38.631 195.237 c
38.185 195.237 37.741 195.053 37.425 194.737 c
37.109 194.421 36.925 193.977 36.925 193.530 c
36.925 193.084 37.109 192.640 37.425 192.324 c
37.741 192.008 38.185 191.824 38.631 191.824 c
39.078 191.824 39.522 192.008 39.838 192.324 c
40.154 192.640 40.337 193.084 40.337 193.530 c f
BT 45.750 190.563 Td /F1 9.8 Tf  [(Retrospective analysis of one arm of a single prospective trial \(NSABP B-20\) showed that chemotherapy \(in addition to )] TJ ET
BT 45.750 178.658 Td /F1 9.8 Tf  [(tamoxifen\) was most beneficial in women in the Oncotype DX high risk category.)] TJ ET
0.267 0.267 0.267 rg
BT 392.548 178.658 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 165.971 m 
40.337 166.417 40.154 166.861 39.838 167.177 c
39.522 167.493 39.078 167.677 38.631 167.677 c
38.185 167.677 37.741 167.493 37.425 167.177 c
37.109 166.861 36.925 166.417 36.925 165.971 c
36.925 165.524 37.109 165.080 37.425 164.764 c
37.741 164.448 38.185 164.265 38.631 164.265 c
39.078 164.265 39.522 164.448 39.838 164.764 c
40.154 165.080 40.337 165.524 40.337 165.971 c f
BT 45.750 163.003 Td /F1 9.8 Tf  [(A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician )] TJ ET
BT 45.750 151.098 Td /F1 9.8 Tf  [(adjuvant chemotherapy decisions.)] TJ ET
0.267 0.267 0.267 rg
BT 193.150 151.098 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
40.337 138.411 m 
40.337 138.858 40.154 139.302 39.838 139.618 c
39.522 139.934 39.078 140.118 38.631 140.118 c
38.185 140.118 37.741 139.934 37.425 139.618 c
37.109 139.302 36.925 138.858 36.925 138.411 c
36.925 137.965 37.109 137.521 37.425 137.205 c
37.741 136.889 38.185 136.705 38.631 136.705 c
39.078 136.705 39.522 136.889 39.838 137.205 c
40.154 137.521 40.337 137.965 40.337 138.411 c f
BT 45.750 135.444 Td /F1 9.8 Tf  [(Analyses of economic implications of Oncotype DX have been published. )] TJ ET
0.267 0.267 0.267 rg
BT 363.853 135.444 Td /F1 9.8 Tf  [([5])] TJ ET
BT 374.695 135.444 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
40.337 122.757 m 
40.337 123.203 40.154 123.647 39.838 123.963 c
39.522 124.279 39.078 124.463 38.631 124.463 c
38.185 124.463 37.741 124.279 37.425 123.963 c
37.109 123.647 36.925 123.203 36.925 122.757 c
36.925 122.310 37.109 121.866 37.425 121.550 c
37.741 121.234 38.185 121.050 38.631 121.050 c
39.078 121.050 39.522 121.234 39.838 121.550 c
40.154 121.866 40.337 122.310 40.337 122.757 c f
BT 45.750 119.789 Td /F1 9.8 Tf  [(2010 publication explored women�s experiences with genomic testing for breast cancer recurrence risk in terms of how )] TJ ET
BT 45.750 107.884 Td /F1 9.8 Tf  [(scores were received and understood.)] TJ ET
0.267 0.267 0.267 rg
BT 211.032 107.884 Td /F1 9.8 Tf  [([27])] TJ ET
0.271 0.267 0.267 rg
40.337 95.197 m 
40.337 95.644 40.154 96.088 39.838 96.404 c
39.522 96.719 39.078 96.903 38.631 96.903 c
38.185 96.903 37.741 96.719 37.425 96.404 c
37.109 96.088 36.925 95.644 36.925 95.197 c
36.925 94.750 37.109 94.306 37.425 93.990 c
37.741 93.675 38.185 93.491 38.631 93.491 c
39.078 93.491 39.522 93.675 39.838 93.990 c
40.154 94.306 40.337 94.750 40.337 95.197 c f
BT 45.750 92.229 Td /F1 9.8 Tf  [(A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical )] TJ ET
BT 45.750 80.325 Td /F1 9.8 Tf  [(outcomes.)] TJ ET
0.267 0.267 0.267 rg
BT 90.727 80.325 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 67.638 m 
40.337 68.084 40.154 68.528 39.838 68.844 c
39.522 69.160 39.078 69.344 38.631 69.344 c
38.185 69.344 37.741 69.160 37.425 68.844 c
37.109 68.528 36.925 68.084 36.925 67.638 c
36.925 67.191 37.109 66.747 37.425 66.431 c
37.741 66.115 38.185 65.931 38.631 65.931 c
39.078 65.931 39.522 66.115 39.838 66.431 c
40.154 66.747 40.337 67.191 40.337 67.638 c f
BT 45.750 64.670 Td /F1 9.8 Tf  [(Ongoing trials include: )] TJ ET
0.39 w 1 J 1 j
59.837 51.983 m 
59.837 52.429 59.654 52.873 59.338 53.189 c
59.022 53.505 58.578 53.689 58.131 53.689 c
57.685 53.689 57.241 53.505 56.925 53.189 c
56.609 52.873 56.425 52.429 56.425 51.983 c
56.425 51.536 56.609 51.092 56.925 50.776 c
57.241 50.460 57.685 50.277 58.131 50.277 c
58.578 50.277 59.022 50.460 59.338 50.776 c
59.654 51.092 59.837 51.536 59.837 51.983 c s
BT 65.250 49.015 Td /F1 9.8 Tf  [(TAILORx trial \(Oncotype DX\))] TJ ET
0.267 0.267 0.267 rg
BT 190.947 49.015 Td /F1 9.8 Tf  [([28])] TJ ET
Q
q
15.000 42.884 577.500 734.116 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(with breast cancer.� )] TJ ET
0.267 0.267 0.267 rg
BT 114.029 755.571 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 736.167 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
0.271 0.267 0.267 RG
40.337 719.730 m 
40.337 720.176 40.154 720.620 39.838 720.936 c
39.522 721.252 39.078 721.436 38.631 721.436 c
38.185 721.436 37.741 721.252 37.425 720.936 c
37.109 720.620 36.925 720.176 36.925 719.730 c
36.925 719.283 37.109 718.839 37.425 718.523 c
37.741 718.207 38.185 718.023 38.631 718.023 c
39.078 718.023 39.522 718.207 39.838 718.523 c
40.154 718.839 40.337 719.283 40.337 719.730 c f
BT 45.750 716.762 Td /F1 9.8 Tf  [(National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology � Breast Cancer )] TJ ET
0.267 0.267 0.267 rg
BT 478.679 716.762 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 494.942 716.762 Td /F1 9.8 Tf  [( American Society )] TJ ET
BT 45.750 704.857 Td /F1 9.8 Tf  [(of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 487.932 704.857 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 504.195 704.857 Td /F1 9.8 Tf  [( ECRI Institute: )] TJ ET
BT 45.750 692.952 Td /F1 9.8 Tf  [(Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 121.615 692.952 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 680.265 m 
40.337 680.712 40.154 681.156 39.838 681.472 c
39.522 681.788 39.078 681.971 38.631 681.971 c
38.185 681.971 37.741 681.788 37.425 681.472 c
37.109 681.156 36.925 680.712 36.925 680.265 c
36.925 679.819 37.109 679.375 37.425 679.059 c
37.741 678.743 38.185 678.559 38.631 678.559 c
39.078 678.559 39.522 678.743 39.838 679.059 c
40.154 679.375 40.337 679.819 40.337 680.265 c f
BT 45.750 677.298 Td /F1 9.8 Tf  [(American Society of Clinical Oncology: 2007 Update of Recommendations for the use of tumor markers in breast cancer )] TJ ET
0.267 0.267 0.267 rg
BT 45.750 665.393 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
40.337 652.706 m 
40.337 653.152 40.154 653.596 39.838 653.912 c
39.522 654.228 39.078 654.412 38.631 654.412 c
38.185 654.412 37.741 654.228 37.425 653.912 c
37.109 653.596 36.925 653.152 36.925 652.706 c
36.925 652.259 37.109 651.815 37.425 651.499 c
37.741 651.183 38.185 651.000 38.631 651.000 c
39.078 651.000 39.522 651.183 39.838 651.499 c
40.154 651.815 40.337 652.259 40.337 652.706 c f
BT 45.750 649.738 Td /F1 9.8 Tf  [(ECRI Institute: Policy Statement )] TJ ET
0.267 0.267 0.267 rg
BT 187.184 649.738 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.583 Td /F5 9.8 Tf  [(* independent groups include the US Preventive Services Task Force \(USPSTF\) and Evaluation of Genomic Applications in )] TJ ET
BT 26.250 614.679 Td /F5 9.8 Tf  [(Practice and Prevention \(EGAPP\) Working Group.)] TJ ET
BT 26.250 578.076 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 558.122 Td /F6 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 558.122 Td /F4 9.8 Tf  [( : )] TJ ET
BT 110.236 558.122 Td /F1 9.8 Tf  [(Test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 546.217 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
40.337 529.780 m 
40.337 530.227 40.154 530.671 39.838 530.987 c
39.522 531.302 39.078 531.486 38.631 531.486 c
38.185 531.486 37.741 531.302 37.425 530.987 c
37.109 530.671 36.925 530.227 36.925 529.780 c
36.925 529.333 37.109 528.889 37.425 528.573 c
37.741 528.258 38.185 528.074 38.631 528.074 c
39.078 528.074 39.522 528.258 39.838 528.573 c
40.154 528.889 40.337 529.333 40.337 529.780 c f
BT 45.750 526.812 Td /F1 9.8 Tf  [(A 2009 EGAPP Working Group recommendation statement )] TJ ET
0.267 0.267 0.267 rg
BT 304.778 526.812 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 315.620 526.812 Td /F1 9.8 Tf  [(suggested that: )] TJ ET
0.39 w 1 J 1 j
59.837 514.125 m 
59.837 514.572 59.654 515.016 59.338 515.332 c
59.022 515.648 58.578 515.831 58.131 515.831 c
57.685 515.831 57.241 515.648 56.925 515.332 c
56.609 515.016 56.425 514.572 56.425 514.125 c
56.425 513.679 56.609 513.235 56.925 512.919 c
57.241 512.603 57.685 512.419 58.131 512.419 c
58.578 512.419 59.022 512.603 59.338 512.919 c
59.654 513.235 59.837 513.679 59.837 514.125 c s
BT 65.250 511.158 Td /F1 9.8 Tf  [(limited published data are available regarding assay performance of clinically available GEP,)] TJ ET
0.39 w 1 J 1 j
59.837 498.470 m 
59.837 498.917 59.654 499.361 59.338 499.677 c
59.022 499.993 58.578 500.177 58.131 500.177 c
57.685 500.177 57.241 499.993 56.925 499.677 c
56.609 499.361 56.425 498.917 56.425 498.470 c
56.425 498.024 56.609 497.580 56.925 497.264 c
57.241 496.948 57.685 496.764 58.131 496.764 c
58.578 496.764 59.022 496.948 59.338 497.264 c
59.654 497.580 59.837 498.024 59.837 498.470 c s
BT 65.250 495.503 Td /F1 9.8 Tf  [(analytic sensitivity and specificity cannot be estimated because no reference technology \(�gold standard�\) is available )] TJ ET
BT 65.250 483.598 Td /F1 9.8 Tf  [(for comparison,)] TJ ET
0.39 w 1 J 1 j
59.837 470.911 m 
59.837 471.358 59.654 471.802 59.338 472.118 c
59.022 472.433 58.578 472.617 58.131 472.617 c
57.685 472.617 57.241 472.433 56.925 472.118 c
56.609 471.802 56.425 471.358 56.425 470.911 c
56.425 470.464 56.609 470.020 56.925 469.704 c
57.241 469.389 57.685 469.205 58.131 469.205 c
58.578 469.205 59.022 469.389 59.338 469.704 c
59.654 470.020 59.837 470.464 59.837 470.911 c s
BT 65.250 467.943 Td /F1 9.8 Tf  [(initial test failure rates ranged from 12-19%, partly because of problems with tissue sampling and processing.)] TJ ET
40.337 451.506 m 
40.337 451.953 40.154 452.397 39.838 452.713 c
39.522 453.029 39.078 453.213 38.631 453.213 c
38.185 453.213 37.741 453.029 37.425 452.713 c
37.109 452.397 36.925 451.953 36.925 451.506 c
36.925 451.060 37.109 450.616 37.425 450.300 c
37.741 449.984 38.185 449.800 38.631 449.800 c
39.078 449.800 39.522 449.984 39.838 450.300 c
40.154 450.616 40.337 451.060 40.337 451.506 c f
BT 45.750 448.539 Td /F1 9.8 Tf  [(One published reference on Oncotype DX analytical validity sponsored by the test manufacturer is available. )] TJ ET
0.267 0.267 0.267 rg
BT 515.047 448.539 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
40.337 435.852 m 
40.337 436.298 40.154 436.742 39.838 437.058 c
39.522 437.374 39.078 437.558 38.631 437.558 c
38.185 437.558 37.741 437.374 37.425 437.058 c
37.109 436.742 36.925 436.298 36.925 435.852 c
36.925 435.405 37.109 434.961 37.425 434.645 c
37.741 434.329 38.185 434.145 38.631 434.145 c
39.078 434.145 39.522 434.329 39.838 434.645 c
40.154 434.961 40.337 435.405 40.337 435.852 c f
BT 45.750 432.884 Td /F1 9.8 Tf  [(he FDA summary of MammaPrint provided information on result and classification accuracy )] TJ ET
0.267 0.267 0.267 rg
BT 442.916 432.884 Td /F1 9.8 Tf  [([16])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 409.729 Td /F6 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 409.729 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 409.729 Td /F1 9.8 Tf  [( Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy )] TJ ET
BT 26.250 397.824 Td /F1 9.8 Tf  [(\(predictive value\).)] TJ ET
40.337 381.387 m 
40.337 381.834 40.154 382.278 39.838 382.594 c
39.522 382.910 39.078 383.094 38.631 383.094 c
38.185 383.094 37.741 382.910 37.425 382.594 c
37.109 382.278 36.925 381.834 36.925 381.387 c
36.925 380.941 37.109 380.497 37.425 380.181 c
37.741 379.865 38.185 379.681 38.631 379.681 c
39.078 379.681 39.522 379.865 39.838 380.181 c
40.154 380.497 40.337 380.941 40.337 381.387 c f
BT 45.750 378.420 Td /F1 9.8 Tf  [(Several studies have reported on the clinical validity for Oncotype DX.)] TJ ET
0.267 0.267 0.267 rg
BT 347.045 378.420 Td /F1 9.8 Tf  [([17])] TJ ET
BT 363.308 378.420 Td /F1 9.8 Tf  [([18])] TJ ET
BT 379.570 378.420 Td /F1 9.8 Tf  [([19])] TJ ET
BT 395.833 378.420 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 365.733 m 
40.337 366.179 40.154 366.623 39.838 366.939 c
39.522 367.255 39.078 367.439 38.631 367.439 c
38.185 367.439 37.741 367.255 37.425 366.939 c
37.109 366.623 36.925 366.179 36.925 365.733 c
36.925 365.286 37.109 364.842 37.425 364.526 c
37.741 364.210 38.185 364.026 38.631 364.026 c
39.078 364.026 39.522 364.210 39.838 364.526 c
40.154 364.842 40.337 365.286 40.337 365.733 c f
BT 45.750 362.765 Td /F1 9.8 Tf  [(A recent study reported an association between the Oncotype DX recurrence score and risk of locoregional recurrence )] TJ ET
BT 45.750 350.860 Td /F1 9.8 Tf  [(using data from the NSABP B-14 and B-20 trials.)] TJ ET
0.267 0.267 0.267 rg
BT 256.555 350.860 Td /F1 9.8 Tf  [([21])] TJ ET
0.271 0.267 0.267 rg
40.337 338.173 m 
40.337 338.620 40.154 339.064 39.838 339.380 c
39.522 339.695 39.078 339.879 38.631 339.879 c
38.185 339.879 37.741 339.695 37.425 339.380 c
37.109 339.064 36.925 338.620 36.925 338.173 c
36.925 337.726 37.109 337.282 37.425 336.966 c
37.741 336.651 38.185 336.467 38.631 336.467 c
39.078 336.467 39.522 336.651 39.838 336.966 c
40.154 337.282 40.337 337.726 40.337 338.173 c f
BT 45.750 335.205 Td /F1 9.8 Tf  [(Published studies regarding MammaPrint have suggested a significant association between the MammaPrint Index \(high )] TJ ET
BT 45.750 323.301 Td /F1 9.8 Tf  [(vs. low risk\) and 5 and 10 year distant recurrence rates.)] TJ ET
0.267 0.267 0.267 rg
BT 285.805 323.301 Td /F1 9.8 Tf  [([22])] TJ ET
BT 302.068 323.301 Td /F1 9.8 Tf  [([23])] TJ ET
BT 318.331 323.301 Td /F1 9.8 Tf  [([24])] TJ ET
0.271 0.267 0.267 rg
BT 334.594 323.301 Td /F1 9.8 Tf  [(However: )] TJ ET
0.39 w 1 J 1 j
59.837 310.614 m 
59.837 311.060 59.654 311.504 59.338 311.820 c
59.022 312.136 58.578 312.320 58.131 312.320 c
57.685 312.320 57.241 312.136 56.925 311.820 c
56.609 311.504 56.425 311.060 56.425 310.614 c
56.425 310.167 56.609 309.723 56.925 309.407 c
57.241 309.091 57.685 308.907 58.131 308.907 c
58.578 308.907 59.022 309.091 59.338 309.407 c
59.654 309.723 59.837 310.167 59.837 310.614 c s
BT 65.250 307.646 Td /F1 9.8 Tf  [(efficacy in ER positive vs. negative cases is unclear,)] TJ ET
0.267 0.267 0.267 rg
BT 290.670 307.646 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
0.39 w 1 J 1 j
59.837 294.959 m 
59.837 295.405 59.654 295.849 59.338 296.165 c
59.022 296.481 58.578 296.665 58.131 296.665 c
57.685 296.665 57.241 296.481 56.925 296.165 c
56.609 295.849 56.425 295.405 56.425 294.959 c
56.425 294.512 56.609 294.068 56.925 293.752 c
57.241 293.436 57.685 293.253 58.131 293.253 c
58.578 293.253 59.022 293.436 59.338 293.752 c
59.654 294.068 59.837 294.512 59.837 294.959 c s
BT 65.250 291.991 Td /F1 9.8 Tf  [(added value beyond standard risk stratification is unclear.)] TJ ET
0.267 0.267 0.267 rg
BT 313.446 291.991 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 275.554 m 
40.337 276.001 40.154 276.445 39.838 276.761 c
39.522 277.076 39.078 277.260 38.631 277.260 c
38.185 277.260 37.741 277.076 37.425 276.761 c
37.109 276.445 36.925 276.001 36.925 275.554 c
36.925 275.107 37.109 274.663 37.425 274.347 c
37.741 274.032 38.185 273.848 38.631 273.848 c
39.078 273.848 39.522 274.032 39.838 274.347 c
40.154 274.663 40.337 275.107 40.337 275.554 c f
BT 45.750 272.586 Td /F1 9.8 Tf  [(A parallel, prospective evaluation was recently published comparing three gene expression profile tests analogous to )] TJ ET
BT 45.750 260.682 Td /F1 9.8 Tf  [(Oncotype DX, Mammaprint and the H:I Ratio Test.)] TJ ET
40.337 247.995 m 
40.337 248.441 40.154 248.885 39.838 249.201 c
39.522 249.517 39.078 249.701 38.631 249.701 c
38.185 249.701 37.741 249.517 37.425 249.201 c
37.109 248.885 36.925 248.441 36.925 247.995 c
36.925 247.548 37.109 247.104 37.425 246.788 c
37.741 246.472 38.185 246.288 38.631 246.288 c
39.078 246.288 39.522 246.472 39.838 246.788 c
40.154 247.104 40.337 247.548 40.337 247.995 c f
BT 45.750 245.027 Td /F1 9.8 Tf  [(All were significantly associated with time to progression; however, concordance of results among the three classifiers was )] TJ ET
BT 45.750 233.122 Td /F1 9.8 Tf  [(relatively low, classifying only 45-61% of patients in the same category.)] TJ ET
0.267 0.267 0.267 rg
BT 352.456 233.122 Td /F1 9.8 Tf  [([25])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 209.967 Td /F4 9.8 Tf  [(Clinical Utility: )] TJ ET
BT 96.684 209.967 Td /F1 9.8 Tf  [(Net benefit of test in improving health outcomes.)] TJ ET
40.337 193.530 m 
40.337 193.977 40.154 194.421 39.838 194.737 c
39.522 195.053 39.078 195.237 38.631 195.237 c
38.185 195.237 37.741 195.053 37.425 194.737 c
37.109 194.421 36.925 193.977 36.925 193.530 c
36.925 193.084 37.109 192.640 37.425 192.324 c
37.741 192.008 38.185 191.824 38.631 191.824 c
39.078 191.824 39.522 192.008 39.838 192.324 c
40.154 192.640 40.337 193.084 40.337 193.530 c f
BT 45.750 190.563 Td /F1 9.8 Tf  [(Retrospective analysis of one arm of a single prospective trial \(NSABP B-20\) showed that chemotherapy \(in addition to )] TJ ET
BT 45.750 178.658 Td /F1 9.8 Tf  [(tamoxifen\) was most beneficial in women in the Oncotype DX high risk category.)] TJ ET
0.267 0.267 0.267 rg
BT 392.548 178.658 Td /F1 9.8 Tf  [([20])] TJ ET
0.271 0.267 0.267 rg
40.337 165.971 m 
40.337 166.417 40.154 166.861 39.838 167.177 c
39.522 167.493 39.078 167.677 38.631 167.677 c
38.185 167.677 37.741 167.493 37.425 167.177 c
37.109 166.861 36.925 166.417 36.925 165.971 c
36.925 165.524 37.109 165.080 37.425 164.764 c
37.741 164.448 38.185 164.265 38.631 164.265 c
39.078 164.265 39.522 164.448 39.838 164.764 c
40.154 165.080 40.337 165.524 40.337 165.971 c f
BT 45.750 163.003 Td /F1 9.8 Tf  [(A prospective multicenter study published in 2010 reported on the impact of Oncotype DX on patient and physician )] TJ ET
BT 45.750 151.098 Td /F1 9.8 Tf  [(adjuvant chemotherapy decisions.)] TJ ET
0.267 0.267 0.267 rg
BT 193.150 151.098 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
40.337 138.411 m 
40.337 138.858 40.154 139.302 39.838 139.618 c
39.522 139.934 39.078 140.118 38.631 140.118 c
38.185 140.118 37.741 139.934 37.425 139.618 c
37.109 139.302 36.925 138.858 36.925 138.411 c
36.925 137.965 37.109 137.521 37.425 137.205 c
37.741 136.889 38.185 136.705 38.631 136.705 c
39.078 136.705 39.522 136.889 39.838 137.205 c
40.154 137.521 40.337 137.965 40.337 138.411 c f
BT 45.750 135.444 Td /F1 9.8 Tf  [(Analyses of economic implications of Oncotype DX have been published. )] TJ ET
0.267 0.267 0.267 rg
BT 363.853 135.444 Td /F1 9.8 Tf  [([5])] TJ ET
BT 374.695 135.444 Td /F1 9.8 Tf  [([26])] TJ ET
0.271 0.267 0.267 rg
40.337 122.757 m 
40.337 123.203 40.154 123.647 39.838 123.963 c
39.522 124.279 39.078 124.463 38.631 124.463 c
38.185 124.463 37.741 124.279 37.425 123.963 c
37.109 123.647 36.925 123.203 36.925 122.757 c
36.925 122.310 37.109 121.866 37.425 121.550 c
37.741 121.234 38.185 121.050 38.631 121.050 c
39.078 121.050 39.522 121.234 39.838 121.550 c
40.154 121.866 40.337 122.310 40.337 122.757 c f
BT 45.750 119.789 Td /F1 9.8 Tf  [(2010 publication explored women�s experiences with genomic testing for breast cancer recurrence risk in terms of how )] TJ ET
BT 45.750 107.884 Td /F1 9.8 Tf  [(scores were received and understood.)] TJ ET
0.267 0.267 0.267 rg
BT 211.032 107.884 Td /F1 9.8 Tf  [([27])] TJ ET
0.271 0.267 0.267 rg
40.337 95.197 m 
40.337 95.644 40.154 96.088 39.838 96.404 c
39.522 96.719 39.078 96.903 38.631 96.903 c
38.185 96.903 37.741 96.719 37.425 96.404 c
37.109 96.088 36.925 95.644 36.925 95.197 c
36.925 94.750 37.109 94.306 37.425 93.990 c
37.741 93.675 38.185 93.491 38.631 93.491 c
39.078 93.491 39.522 93.675 39.838 93.990 c
40.154 94.306 40.337 94.750 40.337 95.197 c f
BT 45.750 92.229 Td /F1 9.8 Tf  [(A 2009 EGAPP recommendation reported that no direct evidence linked the use of MammaPrint or the H:I test to clinical )] TJ ET
BT 45.750 80.325 Td /F1 9.8 Tf  [(outcomes.)] TJ ET
0.267 0.267 0.267 rg
BT 90.727 80.325 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
40.337 67.638 m 
40.337 68.084 40.154 68.528 39.838 68.844 c
39.522 69.160 39.078 69.344 38.631 69.344 c
38.185 69.344 37.741 69.160 37.425 68.844 c
37.109 68.528 36.925 68.084 36.925 67.638 c
36.925 67.191 37.109 66.747 37.425 66.431 c
37.741 66.115 38.185 65.931 38.631 65.931 c
39.078 65.931 39.522 66.115 39.838 66.431 c
40.154 66.747 40.337 67.191 40.337 67.638 c f
BT 45.750 64.670 Td /F1 9.8 Tf  [(Ongoing trials include: )] TJ ET
0.39 w 1 J 1 j
59.837 51.983 m 
59.837 52.429 59.654 52.873 59.338 53.189 c
59.022 53.505 58.578 53.689 58.131 53.689 c
57.685 53.689 57.241 53.505 56.925 53.189 c
56.609 52.873 56.425 52.429 56.425 51.983 c
56.425 51.536 56.609 51.092 56.925 50.776 c
57.241 50.460 57.685 50.277 58.131 50.277 c
58.578 50.277 59.022 50.460 59.338 50.776 c
59.654 51.092 59.837 51.536 59.837 51.983 c s
BT 65.250 49.015 Td /F1 9.8 Tf  [(TAILORx trial \(Oncotype DX\))] TJ ET
0.267 0.267 0.267 rg
BT 190.947 49.015 Td /F1 9.8 Tf  [([28])] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(2)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET
0.39 w 1 J 1 j
Q
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BT 26.250 664.610 Td /F1 9.8 Tf  [(Last updated: June 8, 2010)] TJ ET
BT 26.250 628.007 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 600.553 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 600.553 Td /F1 9.8 Tf  [(Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) Working Group. Recommendations from the )] TJ ET
BT 26.250 588.648 Td /F1 9.8 Tf  [(EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genet Med. )] TJ ET
BT 26.250 576.744 Td /F1 9.8 Tf  [(2009 Jan;11\(1\):66-73. PubMed PMID: 19125125; PubMed Central PMCID: PMC2743614.)] TJ ET
BT 26.250 557.339 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 557.339 Td /F1 9.8 Tf  [(Marchionni L, Wilson RF, Marinopoulos SS, Wolff AC, Parmigiani G, Bass EB, Goodman SN. Impact of gene expression )] TJ ET
BT 26.250 545.434 Td /F1 9.8 Tf  [(profiling tests on breast cancer outcomes. Evid Rep Technol Assess \(Full Rep\). 2007 Dec;\(160\):1-105. Review. PubMed PMID: )] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(18457476.)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 514.125 Td /F1 9.8 Tf  [(Cancer Facts and Figures 2010. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 505.639 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 487.089 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 487.089 Td /F1 9.8 Tf  [(SEER Breast Cancer Statistics. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 478.603 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 460.053 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 460.053 Td /F1 9.8 Tf  [(Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-)] TJ ET
BT 26.250 448.148 Td /F1 9.8 Tf  [(node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care. 2005 May;11\(5\):313-24. Erratum in: )] TJ ET
BT 26.250 436.243 Td /F1 9.8 Tf  [(Am J Manag Care. 2005 Aug;11\(8\):476. PubMed PMID: 15898220.)] TJ ET
BT 26.250 416.838 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 416.838 Td /F1 9.8 Tf  [(Cole BF, Gelber RD, Gelber S, Coates AS, Goldhirsch A. Polychemotherapy for early breast cancer: an overview of the )] TJ ET
BT 26.250 404.934 Td /F1 9.8 Tf  [(randomised clinical trials with quality-adjusted survival analysis. Lancet. 2001 Jul 28;358\(9278\):277-86. Review. PubMed PMID: )] TJ ET
BT 26.250 393.029 Td /F1 9.8 Tf  [(11498214.)] TJ ET
BT 26.250 373.624 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 373.624 Td /F1 9.8 Tf  [(Desch CE, Hillner BE, Smith TJ, Retchin SM. Should the elderly receive chemotherapy for node-negative breast cancer? A )] TJ ET
BT 26.250 361.719 Td /F1 9.8 Tf  [(cost-effectiveness analysis examining total and active life-expectancy outcomes. J Clin Oncol. 1993 Apr;11\(4\):777-82. PubMed )] TJ ET
BT 26.250 349.815 Td /F1 9.8 Tf  [(PMID: 8478671.)] TJ ET
BT 26.250 330.410 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 330.410 Td /F1 9.8 Tf  [(Hillner BE, Smith TJ. Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. )] TJ ET
BT 26.250 318.505 Td /F1 9.8 Tf  [(A decision-analysis model. N Engl J Med. 1991 Jan 17;324\(3\):160-8. PubMed PMID: 1898533.)] TJ ET
BT 26.250 299.100 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 299.100 Td /F1 9.8 Tf  [(Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, Albain KS. )] TJ ET
BT 26.250 287.196 Td /F1 9.8 Tf  [(Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant )] TJ ET
BT 26.250 275.291 Td /F1 9.8 Tf  [(breast cancer treatment selection. J Clin Oncol. 2010 Apr 1;28\(10\):1671-6. Epub 2010 Jan 11. PubMed PMID: 20065191.)] TJ ET
BT 26.250 255.886 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 255.886 Td /F1 9.8 Tf  [(Henry LR, Stojadinovic A, Swain SM, Prindiville S, Cordes R, Soballe PW. The influence of a gene expression profile on )] TJ ET
BT 26.250 243.981 Td /F1 9.8 Tf  [(breast cancer decisions. J Surg Oncol. 2009 May 1;99\(6\):319-23. PubMed PMID: 19204954.)] TJ ET
BT 26.250 224.577 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 224.577 Td /F1 9.8 Tf  [(Piper MA. Gene expression profiling of breast cancer to select women for adjuvant chemotherapy. Technology Evaluation )] TJ ET
BT 26.250 212.672 Td /F1 9.8 Tf  [(Center. Assessment Program 2008;22:1-51. Accessed October 26, 2009:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 204.186 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 185.636 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 185.636 Td /F1 9.8 Tf  [(National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology � Breast Cancer, v 1.2010. )] TJ ET
BT 26.250 173.731 Td /F1 9.8 Tf  [(Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 165.245 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 146.695 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 146.695 Td /F1 9.8 Tf  [(Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr; American Society of )] TJ ET
BT 26.250 134.790 Td /F1 9.8 Tf  [(Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in )] TJ ET
BT 26.250 122.886 Td /F1 9.8 Tf  [(breast cancer. J Clin Oncol. 2007 Nov 20;25\(33\):5287-312. Epub 2007 Oct 22. Review. PubMed PMID: 17954709.)] TJ ET
BT 26.250 103.481 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 103.481 Td /F1 9.8 Tf  [(ECRI Institute, Gene expression profiling of breast cancer to predict the likelihood of recurrence, August 2007. ECRI )] TJ ET
BT 26.250 91.576 Td /F1 9.8 Tf  [(Institute. To subscribers only:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 83.090 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 64.540 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 64.540 Td /F1 9.8 Tf  [(Cronin M, Sangli C, Liu ML, Pho M, Dutta D, Nguyen A, Jeong J, Wu J, Langone KC, Watson D. Analytical validation of the )] TJ ET
BT 26.250 52.635 Td /F1 9.8 Tf  [(Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen )] TJ ET
Q
q
15.000 38.350 577.500 738.650 re W n
0.271 0.267 0.267 rg
0.271 0.267 0.267 RG
0.39 w 1 J 1 j
59.837 770.444 m 
59.837 770.890 59.654 771.334 59.338 771.650 c
59.022 771.966 58.578 772.150 58.131 772.150 c
57.685 772.150 57.241 771.966 56.925 771.650 c
56.609 771.334 56.425 770.890 56.425 770.444 c
56.425 769.997 56.609 769.553 56.925 769.237 c
57.241 768.921 57.685 768.738 58.131 768.738 c
58.578 768.738 59.022 768.921 59.338 769.237 c
59.654 769.553 59.837 769.997 59.837 770.444 c s
BT 65.250 767.476 Td /F1 9.8 Tf  [(INDACT trial \(MammaPrint\))] TJ ET
0.267 0.267 0.267 rg
BT 184.415 767.476 Td /F1 9.8 Tf  [([29])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 723.374 Td /F4 12.0 Tf  [(Links)] TJ ET
BT 26.250 703.419 Td /F1 9.8 Tf  [(For recent additions to the literature, see )] TJ ET
0.267 0.267 0.267 rg
BT 204.002 703.419 Td /F1 9.8 Tf  [(PubMed special query)] TJ ET
0.271 0.267 0.267 rg
BT 300.459 703.419 Td /F1 9.8 Tf  [( \(2007-present\).)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 684.015 Td /F1 9.8 Tf  [(U.S. Food and Drug Administration)] TJ ET
0.271 0.267 0.267 rg
BT 177.434 684.015 Td /F1 9.8 Tf  [( : Search )] TJ ET
0.267 0.267 0.267 rg
BT 219.163 684.015 Td /F1 9.8 Tf  [(FDA 510\(k\) database)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 664.610 Td /F1 9.8 Tf  [(Last updated: June 8, 2010)] TJ ET
BT 26.250 628.007 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 600.553 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 600.553 Td /F1 9.8 Tf  [(Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) Working Group. Recommendations from the )] TJ ET
BT 26.250 588.648 Td /F1 9.8 Tf  [(EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genet Med. )] TJ ET
BT 26.250 576.744 Td /F1 9.8 Tf  [(2009 Jan;11\(1\):66-73. PubMed PMID: 19125125; PubMed Central PMCID: PMC2743614.)] TJ ET
BT 26.250 557.339 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 557.339 Td /F1 9.8 Tf  [(Marchionni L, Wilson RF, Marinopoulos SS, Wolff AC, Parmigiani G, Bass EB, Goodman SN. Impact of gene expression )] TJ ET
BT 26.250 545.434 Td /F1 9.8 Tf  [(profiling tests on breast cancer outcomes. Evid Rep Technol Assess \(Full Rep\). 2007 Dec;\(160\):1-105. Review. PubMed PMID: )] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(18457476.)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 514.125 Td /F1 9.8 Tf  [(Cancer Facts and Figures 2010. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 505.639 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 487.089 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 487.089 Td /F1 9.8 Tf  [(SEER Breast Cancer Statistics. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 478.603 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 460.053 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 460.053 Td /F1 9.8 Tf  [(Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-)] TJ ET
BT 26.250 448.148 Td /F1 9.8 Tf  [(node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care. 2005 May;11\(5\):313-24. Erratum in: )] TJ ET
BT 26.250 436.243 Td /F1 9.8 Tf  [(Am J Manag Care. 2005 Aug;11\(8\):476. PubMed PMID: 15898220.)] TJ ET
BT 26.250 416.838 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 416.838 Td /F1 9.8 Tf  [(Cole BF, Gelber RD, Gelber S, Coates AS, Goldhirsch A. Polychemotherapy for early breast cancer: an overview of the )] TJ ET
BT 26.250 404.934 Td /F1 9.8 Tf  [(randomised clinical trials with quality-adjusted survival analysis. Lancet. 2001 Jul 28;358\(9278\):277-86. Review. PubMed PMID: )] TJ ET
BT 26.250 393.029 Td /F1 9.8 Tf  [(11498214.)] TJ ET
BT 26.250 373.624 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 373.624 Td /F1 9.8 Tf  [(Desch CE, Hillner BE, Smith TJ, Retchin SM. Should the elderly receive chemotherapy for node-negative breast cancer? A )] TJ ET
BT 26.250 361.719 Td /F1 9.8 Tf  [(cost-effectiveness analysis examining total and active life-expectancy outcomes. J Clin Oncol. 1993 Apr;11\(4\):777-82. PubMed )] TJ ET
BT 26.250 349.815 Td /F1 9.8 Tf  [(PMID: 8478671.)] TJ ET
BT 26.250 330.410 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 330.410 Td /F1 9.8 Tf  [(Hillner BE, Smith TJ. Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. )] TJ ET
BT 26.250 318.505 Td /F1 9.8 Tf  [(A decision-analysis model. N Engl J Med. 1991 Jan 17;324\(3\):160-8. PubMed PMID: 1898533.)] TJ ET
BT 26.250 299.100 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 299.100 Td /F1 9.8 Tf  [(Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, Albain KS. )] TJ ET
BT 26.250 287.196 Td /F1 9.8 Tf  [(Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant )] TJ ET
BT 26.250 275.291 Td /F1 9.8 Tf  [(breast cancer treatment selection. J Clin Oncol. 2010 Apr 1;28\(10\):1671-6. Epub 2010 Jan 11. PubMed PMID: 20065191.)] TJ ET
BT 26.250 255.886 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 255.886 Td /F1 9.8 Tf  [(Henry LR, Stojadinovic A, Swain SM, Prindiville S, Cordes R, Soballe PW. The influence of a gene expression profile on )] TJ ET
BT 26.250 243.981 Td /F1 9.8 Tf  [(breast cancer decisions. J Surg Oncol. 2009 May 1;99\(6\):319-23. PubMed PMID: 19204954.)] TJ ET
BT 26.250 224.577 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 224.577 Td /F1 9.8 Tf  [(Piper MA. Gene expression profiling of breast cancer to select women for adjuvant chemotherapy. Technology Evaluation )] TJ ET
BT 26.250 212.672 Td /F1 9.8 Tf  [(Center. Assessment Program 2008;22:1-51. Accessed October 26, 2009:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 204.186 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 185.636 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 185.636 Td /F1 9.8 Tf  [(National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology � Breast Cancer, v 1.2010. )] TJ ET
BT 26.250 173.731 Td /F1 9.8 Tf  [(Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 165.245 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 146.695 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 146.695 Td /F1 9.8 Tf  [(Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr; American Society of )] TJ ET
BT 26.250 134.790 Td /F1 9.8 Tf  [(Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in )] TJ ET
BT 26.250 122.886 Td /F1 9.8 Tf  [(breast cancer. J Clin Oncol. 2007 Nov 20;25\(33\):5287-312. Epub 2007 Oct 22. Review. PubMed PMID: 17954709.)] TJ ET
BT 26.250 103.481 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 103.481 Td /F1 9.8 Tf  [(ECRI Institute, Gene expression profiling of breast cancer to predict the likelihood of recurrence, August 2007. ECRI )] TJ ET
BT 26.250 91.576 Td /F1 9.8 Tf  [(Institute. To subscribers only:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 83.090 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 64.540 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 64.540 Td /F1 9.8 Tf  [(Cronin M, Sangli C, Liu ML, Pho M, Dutta D, Nguyen A, Jeong J, Wu J, Langone KC, Watson D. Analytical validation of the )] TJ ET
BT 26.250 52.635 Td /F1 9.8 Tf  [(Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen )] TJ ET
Q
q
15.000 38.350 577.500 738.650 re W n
0.271 0.267 0.267 rg
0.271 0.267 0.267 RG
0.39 w 1 J 1 j
59.837 770.444 m 
59.837 770.890 59.654 771.334 59.338 771.650 c
59.022 771.966 58.578 772.150 58.131 772.150 c
57.685 772.150 57.241 771.966 56.925 771.650 c
56.609 771.334 56.425 770.890 56.425 770.444 c
56.425 769.997 56.609 769.553 56.925 769.237 c
57.241 768.921 57.685 768.738 58.131 768.738 c
58.578 768.738 59.022 768.921 59.338 769.237 c
59.654 769.553 59.837 769.997 59.837 770.444 c s
BT 65.250 767.476 Td /F1 9.8 Tf  [(INDACT trial \(MammaPrint\))] TJ ET
0.267 0.267 0.267 rg
BT 184.415 767.476 Td /F1 9.8 Tf  [([29])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 723.374 Td /F4 12.0 Tf  [(Links)] TJ ET
BT 26.250 703.419 Td /F1 9.8 Tf  [(For recent additions to the literature, see )] TJ ET
0.267 0.267 0.267 rg
BT 204.002 703.419 Td /F1 9.8 Tf  [(PubMed special query)] TJ ET
0.271 0.267 0.267 rg
BT 300.459 703.419 Td /F1 9.8 Tf  [( \(2007-present\).)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 684.015 Td /F1 9.8 Tf  [(U.S. Food and Drug Administration)] TJ ET
0.271 0.267 0.267 rg
BT 177.434 684.015 Td /F1 9.8 Tf  [( : Search )] TJ ET
0.267 0.267 0.267 rg
BT 219.163 684.015 Td /F1 9.8 Tf  [(FDA 510\(k\) database)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 664.610 Td /F1 9.8 Tf  [(Last updated: June 8, 2010)] TJ ET
BT 26.250 628.007 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 600.553 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 600.553 Td /F1 9.8 Tf  [(Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) Working Group. Recommendations from the )] TJ ET
BT 26.250 588.648 Td /F1 9.8 Tf  [(EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genet Med. )] TJ ET
BT 26.250 576.744 Td /F1 9.8 Tf  [(2009 Jan;11\(1\):66-73. PubMed PMID: 19125125; PubMed Central PMCID: PMC2743614.)] TJ ET
BT 26.250 557.339 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 557.339 Td /F1 9.8 Tf  [(Marchionni L, Wilson RF, Marinopoulos SS, Wolff AC, Parmigiani G, Bass EB, Goodman SN. Impact of gene expression )] TJ ET
BT 26.250 545.434 Td /F1 9.8 Tf  [(profiling tests on breast cancer outcomes. Evid Rep Technol Assess \(Full Rep\). 2007 Dec;\(160\):1-105. Review. PubMed PMID: )] TJ ET
BT 26.250 533.529 Td /F1 9.8 Tf  [(18457476.)] TJ ET
BT 26.250 514.125 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 514.125 Td /F1 9.8 Tf  [(Cancer Facts and Figures 2010. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 505.639 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 487.089 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 487.089 Td /F1 9.8 Tf  [(SEER Breast Cancer Statistics. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 478.603 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 460.053 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 460.053 Td /F1 9.8 Tf  [(Hornberger J, Cosler LE, Lyman GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-)] TJ ET
BT 26.250 448.148 Td /F1 9.8 Tf  [(node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care. 2005 May;11\(5\):313-24. Erratum in: )] TJ ET
BT 26.250 436.243 Td /F1 9.8 Tf  [(Am J Manag Care. 2005 Aug;11\(8\):476. PubMed PMID: 15898220.)] TJ ET
BT 26.250 416.838 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 416.838 Td /F1 9.8 Tf  [(Cole BF, Gelber RD, Gelber S, Coates AS, Goldhirsch A. Polychemotherapy for early breast cancer: an overview of the )] TJ ET
BT 26.250 404.934 Td /F1 9.8 Tf  [(randomised clinical trials with quality-adjusted survival analysis. Lancet. 2001 Jul 28;358\(9278\):277-86. Review. PubMed PMID: )] TJ ET
BT 26.250 393.029 Td /F1 9.8 Tf  [(11498214.)] TJ ET
BT 26.250 373.624 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 373.624 Td /F1 9.8 Tf  [(Desch CE, Hillner BE, Smith TJ, Retchin SM. Should the elderly receive chemotherapy for node-negative breast cancer? A )] TJ ET
BT 26.250 361.719 Td /F1 9.8 Tf  [(cost-effectiveness analysis examining total and active life-expectancy outcomes. J Clin Oncol. 1993 Apr;11\(4\):777-82. PubMed )] TJ ET
BT 26.250 349.815 Td /F1 9.8 Tf  [(PMID: 8478671.)] TJ ET
BT 26.250 330.410 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 330.410 Td /F1 9.8 Tf  [(Hillner BE, Smith TJ. Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. )] TJ ET
BT 26.250 318.505 Td /F1 9.8 Tf  [(A decision-analysis model. N Engl J Med. 1991 Jan 17;324\(3\):160-8. PubMed PMID: 1898533.)] TJ ET
BT 26.250 299.100 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 299.100 Td /F1 9.8 Tf  [(Lo SS, Mumby PB, Norton J, Rychlik K, Smerage J, Kash J, Chew HK, Gaynor ER, Hayes DF, Epstein A, Albain KS. )] TJ ET
BT 26.250 287.196 Td /F1 9.8 Tf  [(Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant )] TJ ET
BT 26.250 275.291 Td /F1 9.8 Tf  [(breast cancer treatment selection. J Clin Oncol. 2010 Apr 1;28\(10\):1671-6. Epub 2010 Jan 11. PubMed PMID: 20065191.)] TJ ET
BT 26.250 255.886 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 255.886 Td /F1 9.8 Tf  [(Henry LR, Stojadinovic A, Swain SM, Prindiville S, Cordes R, Soballe PW. The influence of a gene expression profile on )] TJ ET
BT 26.250 243.981 Td /F1 9.8 Tf  [(breast cancer decisions. J Surg Oncol. 2009 May 1;99\(6\):319-23. PubMed PMID: 19204954.)] TJ ET
BT 26.250 224.577 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 224.577 Td /F1 9.8 Tf  [(Piper MA. Gene expression profiling of breast cancer to select women for adjuvant chemotherapy. Technology Evaluation )] TJ ET
BT 26.250 212.672 Td /F1 9.8 Tf  [(Center. Assessment Program 2008;22:1-51. Accessed October 26, 2009:)] TJ ET
0.267 0.267 0.267 rg
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BT 26.250 721.035 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 721.035 Td /F1 9.8 Tf  [(Habel LA, Shak S, Jacobs MK, Capra A, Alexander C, Pho M, Baker J, Walker M, Watson D, Hackett J, Blick NT, )] TJ ET
BT 26.250 709.131 Td /F1 9.8 Tf  [(Greenberg D, Fehrenbacher L, Langholz B, Quesenberry CP. A population-based study of tumor gene expression and risk of )] TJ ET
BT 26.250 697.226 Td /F1 9.8 Tf  [(breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8\(3\):R25. Epub 2006 May 31. PubMed )] TJ ET
BT 26.250 685.321 Td /F1 9.8 Tf  [(PMID: 16737553; PubMed Central PMCID: PMC1557737.)] TJ ET
BT 26.250 665.916 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 665.916 Td /F1 9.8 Tf  [(Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, )] TJ ET
BT 26.250 654.012 Td /F1 9.8 Tf  [(Wickerham DL, Bryant J, Wolmark N. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast )] TJ ET
BT 26.250 642.107 Td /F1 9.8 Tf  [(cancer. N Engl J Med. 2004 Dec 30;351\(27\):2817-26. Epub 2004 Dec 10. PubMed PMID: 15591335.)] TJ ET
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BT 43.553 622.702 Td /F1 9.8 Tf  [(Esteva FJ, Sahin AA, Cristofanilli M, Coombes K, Lee SJ, Baker J, Cronin M, Walker M, Watson D, Shak S, Hortobagyi GN. )] TJ ET
BT 26.250 610.797 Td /F1 9.8 Tf  [(Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving )] TJ ET
BT 26.250 598.893 Td /F1 9.8 Tf  [(adjuvant systemic therapy. Clin Cancer Res. 2005 May 1;11\(9\):3315-9. PubMed PMID: 15867229.)] TJ ET
BT 26.250 579.488 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 579.488 Td /F1 9.8 Tf  [(Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, )] TJ ET
BT 26.250 567.583 Td /F1 9.8 Tf  [(Wickerham DL, Wolmark N. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-)] TJ ET
BT 26.250 555.678 Td /F1 9.8 Tf  [(positive breast cancer. J Clin Oncol. 2006 Aug 10;24\(23\):3726-34. Epub 2006 May 23. PubMed PMID: 16720680.)] TJ ET
BT 26.250 536.274 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 536.274 Td /F1 9.8 Tf  [(Mamounas EP, Tang G, Fisher B, Paik S, Shak S, Costantino JP, Watson D, Geyer CE Jr, Wickerham DL, Wolmark N. )] TJ ET
BT 26.250 524.369 Td /F1 9.8 Tf  [(Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen )] TJ ET
BT 26.250 512.464 Td /F1 9.8 Tf  [(receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010 Apr 1;28\(10\):1677-83. Epub )] TJ ET
BT 26.250 500.559 Td /F1 9.8 Tf  [(2010 Jan 11. PubMed PMID: 20065188; PubMed Central PMCID: PMC2849763.)] TJ ET
BT 26.250 481.155 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 481.155 Td /F1 9.8 Tf  [(Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, Lahti-Domenici JS, Bruinsma TJ, Warmoes MO, )] TJ ET
BT 26.250 469.250 Td /F1 9.8 Tf  [(Bernards R, Wessels LF, Van't Veer LJ. Converting a breast cancer microarray signature into a high-throughput diagnostic test. )] TJ ET
BT 26.250 457.345 Td /F1 9.8 Tf  [(BMC Genomics. 2006 Oct 30;7:278. PubMed PMID: 17074082; PubMed Central PMCID: PMC1636049.)] TJ ET
BT 26.250 437.940 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 437.940 Td /F1 9.8 Tf  [(Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, )] TJ ET
BT 26.250 426.036 Td /F1 9.8 Tf  [(Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG )] TJ ET
BT 26.250 414.131 Td /F1 9.8 Tf  [(Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl )] TJ ET
BT 26.250 402.226 Td /F1 9.8 Tf  [(Cancer Inst. 2006 Sep 6;98\(17\):1183-92. PubMed PMID: 16954471.)] TJ ET
BT 26.250 382.821 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 382.821 Td /F1 9.8 Tf  [(van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, )] TJ ET
BT 26.250 370.917 Td /F1 9.8 Tf  [(Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical )] TJ ET
BT 26.250 359.012 Td /F1 9.8 Tf  [(outcome of breast cancer. Nature. 2002 Jan 31;415\(6871\):530-6. PubMed PMID: 11823860.)] TJ ET
BT 26.250 339.607 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 339.607 Td /F1 9.8 Tf  [(Kok M, Linn SC, Van Laar RK, Jansen MP, van den Berg TM, Delahaye LJ, Glas AM, Peterse JL, Hauptmann M, Foekens )] TJ ET
BT 26.250 327.702 Td /F1 9.8 Tf  [(JA, Klijn JG, Wessels LF, Van't Veer LJ, Berns EM. Comparison of gene expression profiles predicting progression in breast )] TJ ET
BT 26.250 315.798 Td /F1 9.8 Tf  [(cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2009 Jan;113\(2\):275-83. Epub 2008 Mar 4. PubMed PMID: )] TJ ET
BT 26.250 303.893 Td /F1 9.8 Tf  [(18311582.)] TJ ET
BT 26.250 284.488 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 284.488 Td /F1 9.8 Tf  [(Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic Implications of 21-Gene Breast )] TJ ET
BT 26.250 272.583 Td /F1 9.8 Tf  [(Cancer Risk Assay from the Perspective of an Israeli-Managed Health-Care Organization. Value Health. 2010 Apr 15. [Epub )] TJ ET
BT 26.250 260.679 Td /F1 9.8 Tf  [(ahead of print] PubMed PMID: 20412544.)] TJ ET
BT 26.250 241.274 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 241.274 Td /F1 9.8 Tf  [(Tzeng JP, Mayer D, Richman AR, Lipkus I, Han PK, Valle CG, Carey LA, Brewer NT. Women's experiences with genomic )] TJ ET
BT 26.250 229.369 Td /F1 9.8 Tf  [(testing for breast cancer recurrence risk. Cancer. 2010 Apr 15;116\(8\):1992-2000. PubMed PMID: 20213682.)] TJ ET
BT 26.250 209.964 Td /F1 9.8 Tf  [(28.)] TJ ET
BT 43.553 209.964 Td /F1 9.8 Tf  [(National Cancer Institute, National Institutes of Health. TAILORx Breast Cancer Trial. National Cancer Institute. Accessed )] TJ ET
BT 26.250 198.060 Td /F1 9.8 Tf  [(October 26, 2009:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 189.574 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 171.024 Td /F1 9.8 Tf  [(29.)] TJ ET
BT 43.553 171.024 Td /F1 9.8 Tf  [(European Organisation for Research and Treatment of Cancer. Microarray in node negative disease may avoid )] TJ ET
BT 26.250 159.119 Td /F1 9.8 Tf  [(chemotherapy \(MINDACT\) Trial. European Organisation for Research and Treatment of Cancer. Acessed October 26, 2009:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 150.633 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
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q
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BT 26.250 767.476 Td /F1 9.8 Tf  [(receptor-positive breast cancer. Clin Chem. 2007 Jun;53\(6\):1084-91. Epub 2007 Apr 26. PubMed PMID: 17463177.)] TJ ET
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BT 43.553 748.071 Td /F1 9.8 Tf  [(501\(k\) Submission for MammaPrint Service in the US Section 5: 501\(k\) Summary. Accessed 5/18/10:)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 739.586 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 721.035 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 721.035 Td /F1 9.8 Tf  [(Habel LA, Shak S, Jacobs MK, Capra A, Alexander C, Pho M, Baker J, Walker M, Watson D, Hackett J, Blick NT, )] TJ ET
BT 26.250 709.131 Td /F1 9.8 Tf  [(Greenberg D, Fehrenbacher L, Langholz B, Quesenberry CP. A population-based study of tumor gene expression and risk of )] TJ ET
BT 26.250 697.226 Td /F1 9.8 Tf  [(breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8\(3\):R25. Epub 2006 May 31. PubMed )] TJ ET
BT 26.250 685.321 Td /F1 9.8 Tf  [(PMID: 16737553; PubMed Central PMCID: PMC1557737.)] TJ ET
BT 26.250 665.916 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 665.916 Td /F1 9.8 Tf  [(Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, )] TJ ET
BT 26.250 654.012 Td /F1 9.8 Tf  [(Wickerham DL, Bryant J, Wolmark N. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast )] TJ ET
BT 26.250 642.107 Td /F1 9.8 Tf  [(cancer. N Engl J Med. 2004 Dec 30;351\(27\):2817-26. Epub 2004 Dec 10. PubMed PMID: 15591335.)] TJ ET
BT 26.250 622.702 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 622.702 Td /F1 9.8 Tf  [(Esteva FJ, Sahin AA, Cristofanilli M, Coombes K, Lee SJ, Baker J, Cronin M, Walker M, Watson D, Shak S, Hortobagyi GN. )] TJ ET
BT 26.250 610.797 Td /F1 9.8 Tf  [(Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving )] TJ ET
BT 26.250 598.893 Td /F1 9.8 Tf  [(adjuvant systemic therapy. Clin Cancer Res. 2005 May 1;11\(9\):3315-9. PubMed PMID: 15867229.)] TJ ET
BT 26.250 579.488 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 579.488 Td /F1 9.8 Tf  [(Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, Costantino JP, Geyer CE Jr, )] TJ ET
BT 26.250 567.583 Td /F1 9.8 Tf  [(Wickerham DL, Wolmark N. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-)] TJ ET
BT 26.250 555.678 Td /F1 9.8 Tf  [(positive breast cancer. J Clin Oncol. 2006 Aug 10;24\(23\):3726-34. Epub 2006 May 23. PubMed PMID: 16720680.)] TJ ET
BT 26.250 536.274 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 536.274 Td /F1 9.8 Tf  [(Mamounas EP, Tang G, Fisher B, Paik S, Shak S, Costantino JP, Watson D, Geyer CE Jr, Wickerham DL, Wolmark N. )] TJ ET
BT 26.250 524.369 Td /F1 9.8 Tf  [(Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen )] TJ ET
BT 26.250 512.464 Td /F1 9.8 Tf  [(receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010 Apr 1;28\(10\):1677-83. Epub )] TJ ET
BT 26.250 500.559 Td /F1 9.8 Tf  [(2010 Jan 11. PubMed PMID: 20065188; PubMed Central PMCID: PMC2849763.)] TJ ET
BT 26.250 481.155 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 481.155 Td /F1 9.8 Tf  [(Glas AM, Floore A, Delahaye LJ, Witteveen AT, Pover RC, Bakx N, Lahti-Domenici JS, Bruinsma TJ, Warmoes MO, )] TJ ET
BT 26.250 469.250 Td /F1 9.8 Tf  [(Bernards R, Wessels LF, Van't Veer LJ. Converting a breast cancer microarray signature into a high-throughput diagnostic test. )] TJ ET
BT 26.250 457.345 Td /F1 9.8 Tf  [(BMC Genomics. 2006 Oct 30;7:278. PubMed PMID: 17074082; PubMed Central PMCID: PMC1636049.)] TJ ET
BT 26.250 437.940 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 437.940 Td /F1 9.8 Tf  [(Buyse M, Loi S, van't Veer L, Viale G, Delorenzi M, Glas AM, d'Assignies MS, Bergh J, Lidereau R, Ellis P, Harris A, )] TJ ET
BT 26.250 426.036 Td /F1 9.8 Tf  [(Bogaerts J, Therasse P, Floore A, Amakrane M, Piette F, Rutgers E, Sotiriou C, Cardoso F, Piccart MJ; TRANSBIG )] TJ ET
BT 26.250 414.131 Td /F1 9.8 Tf  [(Consortium. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl )] TJ ET
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BT 43.553 382.821 Td /F1 9.8 Tf  [(van 't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, )] TJ ET
BT 26.250 370.917 Td /F1 9.8 Tf  [(Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical )] TJ ET
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BT 43.553 339.607 Td /F1 9.8 Tf  [(Kok M, Linn SC, Van Laar RK, Jansen MP, van den Berg TM, Delahaye LJ, Glas AM, Peterse JL, Hauptmann M, Foekens )] TJ ET
BT 26.250 327.702 Td /F1 9.8 Tf  [(JA, Klijn JG, Wessels LF, Van't Veer LJ, Berns EM. Comparison of gene expression profiles predicting progression in breast )] TJ ET
BT 26.250 315.798 Td /F1 9.8 Tf  [(cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2009 Jan;113\(2\):275-83. Epub 2008 Mar 4. PubMed PMID: )] TJ ET
BT 26.250 303.893 Td /F1 9.8 Tf  [(18311582.)] TJ ET
BT 26.250 284.488 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 284.488 Td /F1 9.8 Tf  [(Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic Implications of 21-Gene Breast )] TJ ET
BT 26.250 272.583 Td /F1 9.8 Tf  [(Cancer Risk Assay from the Perspective of an Israeli-Managed Health-Care Organization. Value Health. 2010 Apr 15. [Epub )] TJ ET
BT 26.250 260.679 Td /F1 9.8 Tf  [(ahead of print] PubMed PMID: 20412544.)] TJ ET
BT 26.250 241.274 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 241.274 Td /F1 9.8 Tf  [(Tzeng JP, Mayer D, Richman AR, Lipkus I, Han PK, Valle CG, Carey LA, Brewer NT. Women's experiences with genomic )] TJ ET
BT 26.250 229.369 Td /F1 9.8 Tf  [(testing for breast cancer recurrence risk. Cancer. 2010 Apr 15;116\(8\):1992-2000. PubMed PMID: 20213682.)] TJ ET
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BT 43.553 209.964 Td /F1 9.8 Tf  [(National Cancer Institute, National Institutes of Health. TAILORx Breast Cancer Trial. National Cancer Institute. Accessed )] TJ ET
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BT 26.250 189.574 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
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