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BT 15.000 718.042 Td /F2 21.0 Tf  [(Use of Oncotype DX in Women with Node-Positive Breast )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(Cancer)] TJ ET
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BT 15.000 675.088 Td /F3 9.8 Tf  [(July 21, 2011)] TJ ET
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BT 26.250 663.247 Td /F1 9.8 Tf  [(Naoko Ishibe)] TJ ET
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BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy to prevent recurrence; however, not all )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(patients benefit. Recently, gene expression marker panels, such as Oncotype DX, that may better predict risk of breast cancer )] TJ ET
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BT 26.250 482.350 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy based on standard recurrence risk )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(classification using lymph node status and qualitative tumor characteristics, such as size, type, grade, receptor status, and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(histology. These classifiers identify very few women who are at low risk of recurrence and as a result, more patients are treated )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(with chemotherapy than those who will benefit. Panels of gene expression markers�such as Oncotype DX )] TJ ET
BT 490.116 430.570 Td /F1 8.7 Tf  [(TM�)] TJ ET
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BT 26.250 402.872 Td /F1 9.8 Tf  [(decisions in women with lymph node-negative breast cancer. However, it is not clear whether Oncotype DX can accurately )] TJ ET
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BT 26.250 352.158 Td /F1 9.8 Tf  [(Oncotype DX )] TJ ET
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BT 26.250 340.253 Td /F1 9.8 Tf  [(recurrence score \(RS\) using reverse transcription PCR in formalin-fixed, paraffin-embedded breast cancer tissue samples. The )] TJ ET
BT 26.250 328.348 Td /F1 9.8 Tf  [(RS is a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the )] TJ ET
BT 26.250 316.443 Td /F1 9.8 Tf  [(initial diagnosis, as well as response to adjuvant treatment. Using recurrence score, it may be possible for healthcare providers )] TJ ET
BT 26.250 304.539 Td /F1 9.8 Tf  [(and patients to determine whether adjuvant chemotherapy is needed following primary therapy for breast cancer.)] TJ ET
BT 26.250 285.134 Td /F4 9.8 Tf  [(Public Health Importance)] TJ ET
BT 26.250 265.729 Td /F1 9.8 Tf  [(Breast cancer is the most commonly diagnosed cancer in U.S. women and is the second leading cause of cancer-related )] TJ ET
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BT 103.763 253.824 Td /F1 9.8 Tf  [( . Although breast cancer patients frequently receive adjuvant chemotherapy to prevent recurrence, not all )] TJ ET
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BT 26.250 230.015 Td /F1 9.8 Tf  [(low likelihood of recurrence and thus may choose to avoid the potential toxicity and morbidity of chemotherapy.)] TJ ET
BT 26.250 210.610 Td /F4 9.8 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
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BT 83.151 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 236.499 663.247 Td /F1 9.8 Tf  [(Scott David Ramsey)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Ishibe N, Schully S, Freedman A, Ramsey SD. Use of Oncotype DX in Women with Node-Positive Breast Cancer. PLOS )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Currents Evidence on Genomic Tests. 2011 Jul 21 . Edition 1. doi: 10.1371/currents.RRN1249.)] TJ ET
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BT 26.250 590.381 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy to prevent recurrence; however, not all )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(patients benefit. Recently, gene expression marker panels, such as Oncotype DX, that may better predict risk of breast cancer )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(recurrence have become commercially available and are being used to guide treatment decisions. Oncotype DX analyzes the )] TJ ET
BT 26.250 554.667 Td /F1 9.8 Tf  [(expression of 21 genes within a tumor to determine a recurrence score that corresponds to a specific likelihood of breast cancer )] TJ ET
BT 26.250 542.762 Td /F1 9.8 Tf  [(recurrence within 10 years of the initial diagnosis, as well as response to adjuvant treatment. We examined the published )] TJ ET
BT 26.250 530.857 Td /F1 9.8 Tf  [(literature on the analytic validity, clinical validity, and clinical utility of Oncotype DX in guiding adjuvant treatment decisions in )] TJ ET
BT 26.250 518.952 Td /F1 9.8 Tf  [(women with lymph node-positive breast cancer.)] TJ ET
BT 26.250 482.350 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy based on standard recurrence risk )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(classification using lymph node status and qualitative tumor characteristics, such as size, type, grade, receptor status, and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(histology. These classifiers identify very few women who are at low risk of recurrence and as a result, more patients are treated )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(with chemotherapy than those who will benefit. Panels of gene expression markers�such as Oncotype DX )] TJ ET
BT 490.116 430.570 Td /F1 8.7 Tf  [(TM�)] TJ ET
BT 511.297 426.681 Td /F1 9.8 Tf  [( are marketed )] TJ ET
BT 26.250 414.777 Td /F1 9.8 Tf  [(to physicians and patients for having the benefit of better predicting risk of breast cancer recurrence and to guide treatment )] TJ ET
BT 26.250 402.872 Td /F1 9.8 Tf  [(decisions in women with lymph node-negative breast cancer. However, it is not clear whether Oncotype DX can accurately )] TJ ET
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BT 26.250 352.158 Td /F1 9.8 Tf  [(Oncotype DX )] TJ ET
BT 86.944 356.046 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 99.458 352.158 Td /F1 9.8 Tf  [( analyzes the expression of 21 genes \(16 cancer-related and 5 normative genes\) within a tumor to determine a )] TJ ET
BT 26.250 340.253 Td /F1 9.8 Tf  [(recurrence score \(RS\) using reverse transcription PCR in formalin-fixed, paraffin-embedded breast cancer tissue samples. The )] TJ ET
BT 26.250 328.348 Td /F1 9.8 Tf  [(RS is a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the )] TJ ET
BT 26.250 316.443 Td /F1 9.8 Tf  [(initial diagnosis, as well as response to adjuvant treatment. Using recurrence score, it may be possible for healthcare providers )] TJ ET
BT 26.250 304.539 Td /F1 9.8 Tf  [(and patients to determine whether adjuvant chemotherapy is needed following primary therapy for breast cancer.)] TJ ET
BT 26.250 285.134 Td /F4 9.8 Tf  [(Public Health Importance)] TJ ET
BT 26.250 265.729 Td /F1 9.8 Tf  [(Breast cancer is the most commonly diagnosed cancer in U.S. women and is the second leading cause of cancer-related )] TJ ET
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BT 103.763 253.824 Td /F1 9.8 Tf  [( . Although breast cancer patients frequently receive adjuvant chemotherapy to prevent recurrence, not all )] TJ ET
BT 26.250 241.920 Td /F1 9.8 Tf  [(patients benefit. Gene expression tests may aid in chemotherapy decision-making. Specifically, women with low RS may have )] TJ ET
BT 26.250 230.015 Td /F1 9.8 Tf  [(low likelihood of recurrence and thus may choose to avoid the potential toxicity and morbidity of chemotherapy.)] TJ ET
BT 26.250 210.610 Td /F4 9.8 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 191.205 Td /F4 9.8 Tf  [(Systematic evidence reviews/ technology assessments)] TJ ET
0.271 0.267 0.267 RG
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40.337 175.215 40.154 175.659 39.838 175.975 c
39.522 176.291 39.078 176.475 38.631 176.475 c
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37.109 175.659 36.925 175.215 36.925 174.768 c
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38.185 133.915 37.741 133.731 37.425 133.415 c
37.109 133.099 36.925 132.655 36.925 132.209 c
36.925 131.762 37.109 131.318 37.425 131.002 c
37.741 130.686 38.185 130.503 38.631 130.503 c
39.078 130.503 39.522 130.686 39.838 131.002 c
40.154 131.318 40.337 131.762 40.337 132.209 c f
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40.337 90.096 40.154 90.540 39.838 90.856 c
39.522 91.172 39.078 91.356 38.631 91.356 c
38.185 91.356 37.741 91.172 37.425 90.856 c
37.109 90.540 36.925 90.096 36.925 89.649 c
36.925 89.203 37.109 88.759 37.425 88.443 c
37.741 88.127 38.185 87.943 38.631 87.943 c
39.078 87.943 39.522 88.127 39.838 88.443 c
40.154 88.759 40.337 89.203 40.337 89.649 c f
BT 45.750 86.682 Td /F1 9.8 Tf  [(None identified.)] TJ ET
BT 26.250 63.527 Td /F1 9.8 Tf  [(With the exception of BCBS TEC, none of the professional or independent groups evaluated Oncotype DX for lymph node-)] TJ ET
BT 26.250 51.622 Td /F1 9.8 Tf  [(positive breast cancer. BCBS TEC concluded that there is insufficient evidence to determine the clinical validity or utility of )] TJ ET
BT 26.250 39.717 Td /F1 9.8 Tf  [(Oncotype DX as a predictor of breast cancer recurrence or response to adjuvant chemotherapy in patients with node-positive )] TJ ET
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BT 26.250 663.247 Td /F1 9.8 Tf  [(Naoko Ishibe)] TJ ET
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BT 83.151 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 88.572 663.247 Td /F1 9.8 Tf  [(Sheri Schully)] TJ ET
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BT 150.884 663.247 Td /F1 9.8 Tf  [(Andrew Freedman)] TJ ET
0.271 0.267 0.267 rg
BT 231.078 663.247 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 236.499 663.247 Td /F1 9.8 Tf  [(Scott David Ramsey)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 651.342 Td /F1 9.8 Tf  [(Ishibe N, Schully S, Freedman A, Ramsey SD. Use of Oncotype DX in Women with Node-Positive Breast Cancer. PLOS )] TJ ET
BT 26.250 639.438 Td /F1 9.8 Tf  [(Currents Evidence on Genomic Tests. 2011 Jul 21 . Edition 1. doi: 10.1371/currents.RRN1249.)] TJ ET
q
15.000 25.432 577.500 611.625 re W n
0.271 0.267 0.267 rg
BT 26.250 610.335 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 590.381 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy to prevent recurrence; however, not all )] TJ ET
BT 26.250 578.476 Td /F1 9.8 Tf  [(patients benefit. Recently, gene expression marker panels, such as Oncotype DX, that may better predict risk of breast cancer )] TJ ET
BT 26.250 566.571 Td /F1 9.8 Tf  [(recurrence have become commercially available and are being used to guide treatment decisions. Oncotype DX analyzes the )] TJ ET
BT 26.250 554.667 Td /F1 9.8 Tf  [(expression of 21 genes within a tumor to determine a recurrence score that corresponds to a specific likelihood of breast cancer )] TJ ET
BT 26.250 542.762 Td /F1 9.8 Tf  [(recurrence within 10 years of the initial diagnosis, as well as response to adjuvant treatment. We examined the published )] TJ ET
BT 26.250 530.857 Td /F1 9.8 Tf  [(literature on the analytic validity, clinical validity, and clinical utility of Oncotype DX in guiding adjuvant treatment decisions in )] TJ ET
BT 26.250 518.952 Td /F1 9.8 Tf  [(women with lymph node-positive breast cancer.)] TJ ET
BT 26.250 482.350 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 462.396 Td /F1 9.8 Tf  [(Women with early stage breast cancer frequently receive adjuvant chemotherapy based on standard recurrence risk )] TJ ET
BT 26.250 450.491 Td /F1 9.8 Tf  [(classification using lymph node status and qualitative tumor characteristics, such as size, type, grade, receptor status, and )] TJ ET
BT 26.250 438.586 Td /F1 9.8 Tf  [(histology. These classifiers identify very few women who are at low risk of recurrence and as a result, more patients are treated )] TJ ET
BT 26.250 426.681 Td /F1 9.8 Tf  [(with chemotherapy than those who will benefit. Panels of gene expression markers�such as Oncotype DX )] TJ ET
BT 490.116 430.570 Td /F1 8.7 Tf  [(TM�)] TJ ET
BT 511.297 426.681 Td /F1 9.8 Tf  [( are marketed )] TJ ET
BT 26.250 414.777 Td /F1 9.8 Tf  [(to physicians and patients for having the benefit of better predicting risk of breast cancer recurrence and to guide treatment )] TJ ET
BT 26.250 402.872 Td /F1 9.8 Tf  [(decisions in women with lymph node-negative breast cancer. However, it is not clear whether Oncotype DX can accurately )] TJ ET
BT 26.250 390.967 Td /F1 9.8 Tf  [(assess risk of disease recurrence in women with lymph node-positive breast cancer.)] TJ ET
BT 26.250 371.562 Td /F4 9.8 Tf  [(Test Description)] TJ ET
BT 26.250 352.158 Td /F1 9.8 Tf  [(Oncotype DX )] TJ ET
BT 86.944 356.046 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 99.458 352.158 Td /F1 9.8 Tf  [( analyzes the expression of 21 genes \(16 cancer-related and 5 normative genes\) within a tumor to determine a )] TJ ET
BT 26.250 340.253 Td /F1 9.8 Tf  [(recurrence score \(RS\) using reverse transcription PCR in formalin-fixed, paraffin-embedded breast cancer tissue samples. The )] TJ ET
BT 26.250 328.348 Td /F1 9.8 Tf  [(RS is a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the )] TJ ET
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BT 26.250 304.539 Td /F1 9.8 Tf  [(and patients to determine whether adjuvant chemotherapy is needed following primary therapy for breast cancer.)] TJ ET
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0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(breast cancer.)] TJ ET
BT 26.250 730.874 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 710.919 Td /F5 9.8 Tf  [(Analytical Validity)] TJ ET
BT 109.700 710.919 Td /F4 9.8 Tf  [( : )] TJ ET
BT 118.368 710.919 Td /F1 9.8 Tf  [( test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 699.015 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
0.271 0.267 0.267 RG
40.337 682.577 m 
40.337 683.024 40.154 683.468 39.838 683.784 c
39.522 684.100 39.078 684.284 38.631 684.284 c
38.185 684.284 37.741 684.100 37.425 683.784 c
37.109 683.468 36.925 683.024 36.925 682.577 c
36.925 682.131 37.109 681.687 37.425 681.371 c
37.741 681.055 38.185 680.871 38.631 680.871 c
39.078 680.871 39.522 681.055 39.838 681.371 c
40.154 681.687 40.337 682.131 40.337 682.577 c f
BT 45.750 679.610 Td /F1 9.8 Tf  [(Based on evaluation by EGAPP)] TJ ET
0.267 0.267 0.267 rg
BT 183.410 679.610 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 194.252 679.610 Td /F1 9.8 Tf  [(, because there is no referent technology, it is not possible to estimate the false positive )] TJ ET
BT 45.750 667.705 Td /F1 9.8 Tf  [(or false negative rates of the test. Based on seven studies, testing initially failed in 14.5% of samples due to insufficient )] TJ ET
BT 45.750 655.800 Td /F1 9.8 Tf  [(tumor content, poor RNA samples, and RT-PCR failure. However, no studies have been conducted in node-positive breast )] TJ ET
BT 45.750 643.896 Td /F1 9.8 Tf  [(cancer patients.)] TJ ET
40.337 631.208 m 
40.337 631.655 40.154 632.099 39.838 632.415 c
39.522 632.731 39.078 632.915 38.631 632.915 c
38.185 632.915 37.741 632.731 37.425 632.415 c
37.109 632.099 36.925 631.655 36.925 631.208 c
36.925 630.762 37.109 630.318 37.425 630.002 c
37.741 629.686 38.185 629.502 38.631 629.502 c
39.078 629.502 39.522 629.686 39.838 630.002 c
40.154 630.318 40.337 630.762 40.337 631.208 c f
BT 45.750 628.241 Td /F1 9.8 Tf  [(Cronin et al.)] TJ ET
0.267 0.267 0.267 rg
BT 98.312 628.241 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 109.154 628.241 Td /F1 9.8 Tf  [(assessed the amplification efficiency, linearity, quantification limitations, dynamic range, analytical precision, )] TJ ET
BT 45.750 616.336 Td /F1 9.8 Tf  [(and reproducibility performance of Oncotype DX. The authors reported that the reproducibility of the recurrence score was )] TJ ET
BT 45.750 604.431 Td /F1 9.8 Tf  [(very high with repeat testing of de-identified patient samples \(standard deviation of less than 2 recurrence score units\).)] TJ ET
BT 26.250 581.277 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 581.277 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 581.277 Td /F1 9.8 Tf  [( test accuracy and reliability in predicting recurrence in node-positive breast cancer patients \(prognosis\) and )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(benefit from chemotherapy \(predictive\).)] TJ ET
40.337 552.935 m 
40.337 553.381 40.154 553.825 39.838 554.141 c
39.522 554.457 39.078 554.641 38.631 554.641 c
38.185 554.641 37.741 554.457 37.425 554.141 c
37.109 553.825 36.925 553.381 36.925 552.935 c
36.925 552.488 37.109 552.044 37.425 551.728 c
37.741 551.412 38.185 551.228 38.631 551.228 c
39.078 551.228 39.522 551.412 39.838 551.728 c
40.154 552.044 40.337 552.488 40.337 552.935 c f
BT 45.750 549.967 Td /F1 9.8 Tf  [(Retrospective analysis of the phase 3 trial SWOG-8814 reported on the clinical validity of Oncotype DX)] TJ ET
BT 489.560 553.855 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 502.075 549.967 Td /F1 9.8 Tf  [(in women who )] TJ ET
BT 45.750 538.062 Td /F1 9.8 Tf  [(had node-positive breast cancer and were treated with tamoxifen alone)] TJ ET
0.267 0.267 0.267 rg
BT 351.939 538.062 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 362.781 538.062 Td /F1 9.8 Tf  [(. The authors state that the study suggests that )] TJ ET
BT 45.750 526.158 Td /F1 9.8 Tf  [(patients with node-positive breast cancer with a low recurrence score do not seem to benefit from adjuvant chemotherapy )] TJ ET
BT 45.750 514.253 Td /F1 9.8 Tf  [(\(hazard ratio [HR]=1.02, 95% confidence interval [CI] = 0.54-1.93\), whereas those with a high recurrence score show an )] TJ ET
BT 45.750 502.348 Td /F1 9.8 Tf  [(improvement in disease-free survival, independent of the number of positive nodes \(HR=0.59, 95% CI = 0.35-1.01\). The RS )] TJ ET
BT 45.750 490.443 Td /F1 9.8 Tf  [(was also prognostic in the tamoxifen-alone group \(HR=2.64, 95% CI � 1.33 -5.27, for a 50-point difference in RS\).)] TJ ET
40.337 477.756 m 
40.337 478.203 40.154 478.647 39.838 478.963 c
39.522 479.279 39.078 479.462 38.631 479.462 c
38.185 479.462 37.741 479.279 37.425 478.963 c
37.109 478.647 36.925 478.203 36.925 477.756 c
36.925 477.310 37.109 476.866 37.425 476.550 c
37.741 476.234 38.185 476.050 38.631 476.050 c
39.078 476.050 39.522 476.234 39.838 476.550 c
40.154 476.866 40.337 477.310 40.337 477.756 c f
BT 45.750 474.789 Td /F1 9.8 Tf  [(Dowsett et al.)] TJ ET
0.267 0.267 0.267 rg
BT 104.816 474.789 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
BT 115.657 474.789 Td /F1 9.8 Tf  [(evaluated whether the recurrence score based on Oncotype DX provided independent information on risk )] TJ ET
BT 45.750 462.884 Td /F1 9.8 Tf  [(of distant recurrence in the tamoxifen and anastrozole arms of the ATAC Trial. The authors reported that recurrence score )] TJ ET
BT 45.750 450.979 Td /F1 9.8 Tf  [(is an independent prognosticator of recurrence in node-positive \(as well as node-negative\) breast cancer patients )] TJ ET
BT 45.750 439.074 Td /F1 9.8 Tf  [(\(HR=3.47, 95% CI = 1.64-7.38, for a 50-point difference in RS\) and concluded that it provides additional information to risk )] TJ ET
BT 45.750 427.170 Td /F1 9.8 Tf  [(determined using standard clinicopathologic features.)] TJ ET
BT 26.250 404.015 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
BT 90.727 404.015 Td /F4 9.8 Tf  [( : )] TJ ET
BT 99.394 404.015 Td /F1 9.8 Tf  [( net benefit of test in improving health outcomes.)] TJ ET
40.337 387.578 m 
40.337 388.024 40.154 388.468 39.838 388.784 c
39.522 389.100 39.078 389.284 38.631 389.284 c
38.185 389.284 37.741 389.100 37.425 388.784 c
37.109 388.468 36.925 388.024 36.925 387.578 c
36.925 387.131 37.109 386.687 37.425 386.371 c
37.741 386.055 38.185 385.872 38.631 385.872 c
39.078 385.872 39.522 386.055 39.838 386.371 c
40.154 386.687 40.337 387.131 40.337 387.578 c f
BT 45.750 384.610 Td /F1 9.8 Tf  [(No prospective studies assessing clinical utility have been conducted in women with node-positive breast cancer.)] TJ ET
40.337 371.923 m 
40.337 372.370 40.154 372.814 39.838 373.130 c
39.522 373.445 39.078 373.629 38.631 373.629 c
38.185 373.629 37.741 373.445 37.425 373.130 c
37.109 372.814 36.925 372.370 36.925 371.923 c
36.925 371.476 37.109 371.032 37.425 370.716 c
37.741 370.401 38.185 370.217 38.631 370.217 c
39.078 370.217 39.522 370.401 39.838 370.716 c
40.154 371.032 40.337 371.476 40.337 371.923 c f
BT 45.750 368.955 Td /F1 9.8 Tf  [(It is not clear whether recurrence scores for women with lymph-node positive breast cancer derived by the use of Oncotype )] TJ ET
BT 45.750 357.051 Td /F1 9.8 Tf  [(DX improves health outcome beyond current standard clinical classification methods)] TJ ET
0.267 0.267 0.267 rg
BT 409.347 357.051 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 420.189 357.051 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 344.364 m 
40.337 344.810 40.154 345.254 39.838 345.570 c
39.522 345.886 39.078 346.070 38.631 346.070 c
38.185 346.070 37.741 345.886 37.425 345.570 c
37.109 345.254 36.925 344.810 36.925 344.364 c
36.925 343.917 37.109 343.473 37.425 343.157 c
37.741 342.841 38.185 342.657 38.631 342.657 c
39.078 342.657 39.522 342.841 39.838 343.157 c
40.154 343.473 40.337 343.917 40.337 344.364 c f
BT 45.750 341.396 Td /F1 9.8 Tf  [(SWOG S-1007, a prospective, randomized trial to determine the effect of chemotherapy in patients with 1-3 positive nodes, )] TJ ET
BT 45.750 329.491 Td /F1 9.8 Tf  [(and hormone receptor-positive, HER2-negative breast cancer who do not have high RS by Oncotype DX. This trial, which )] TJ ET
BT 45.750 317.586 Td /F1 9.8 Tf  [(is scheduled to be completed in 2016 will provide evidence regarding the clinical utility of Oncotype DX)] TJ ET
0.267 0.267 0.267 rg
BT 487.942 317.586 Td /F1 9.8 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 498.784 317.586 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 294.432 Td /F4 9.8 Tf  [(Limitations)] TJ ET
40.337 277.995 m 
40.337 278.441 40.154 278.885 39.838 279.201 c
39.522 279.517 39.078 279.701 38.631 279.701 c
38.185 279.701 37.741 279.517 37.425 279.201 c
37.109 278.885 36.925 278.441 36.925 277.995 c
36.925 277.548 37.109 277.104 37.425 276.788 c
37.741 276.472 38.185 276.288 38.631 276.288 c
39.078 276.288 39.522 276.472 39.838 276.788 c
40.154 277.104 40.337 277.548 40.337 277.995 c f
BT 45.750 275.027 Td /F1 9.8 Tf  [(There is currently no data clearly demonstrating clinical utility of Oncotype DX in women with lymph node-positive breast )] TJ ET
BT 45.750 263.122 Td /F1 9.8 Tf  [(cancer.)] TJ ET
BT 26.250 222.770 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 202.815 Td /F1 9.8 Tf  [(Recently, gene expression marker panels that may better predict risk of breast cancer recurrence have become commercially )] TJ ET
BT 26.250 190.911 Td /F1 9.8 Tf  [(available and are being used to guide treatment decisions in women with node-negative breast cancer. This has led to one )] TJ ET
BT 26.250 179.006 Td /F1 9.8 Tf  [(prospective, randomized controlled study specifically focused on women with lymph node-positive breast cancer to assess )] TJ ET
BT 26.250 167.101 Td /F1 9.8 Tf  [(whether those panels can better predict recurrence in those patients as well. Although there is some evidence to suggest that )] TJ ET
BT 26.250 155.196 Td /F1 9.8 Tf  [(the use of Oncotype DX can provide additional information in predicting recurrence in women with lymph node-positive breast )] TJ ET
BT 26.250 143.292 Td /F1 9.8 Tf  [(cancer, there are currently no data from prospective clinical trials assessing the relative clinical benefit of OncotypeDX-guided )] TJ ET
BT 26.250 131.387 Td /F1 9.8 Tf  [(therapy vs. current care in those women. Therefore, it is unclear whether results of the gene expression panel can be used to )] TJ ET
BT 26.250 119.482 Td /F1 9.8 Tf  [(withhold chemotherapy for a portion of women who otherwise would receive it as part of therapy. Thus, current data cannot )] TJ ET
BT 26.250 107.577 Td /F1 9.8 Tf  [(answer the question of whether Oncotype Dx-guided practice improves health outcomes beyond standard clinical practice.)] TJ ET
BT 26.250 88.173 Td /F4 9.8 Tf  [(Links)] TJ ET
BT 26.250 68.768 Td /F1 9.8 Tf  [(Last updated: July 21, 2011)] TJ ET
BT 26.250 49.363 Td /F4 9.8 Tf  [(Acknowledgements)] TJ ET
Q
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0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(breast cancer.)] TJ ET
BT 26.250 730.874 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 710.919 Td /F5 9.8 Tf  [(Analytical Validity)] TJ ET
BT 109.700 710.919 Td /F4 9.8 Tf  [( : )] TJ ET
BT 118.368 710.919 Td /F1 9.8 Tf  [( test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 699.015 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
0.271 0.267 0.267 RG
40.337 682.577 m 
40.337 683.024 40.154 683.468 39.838 683.784 c
39.522 684.100 39.078 684.284 38.631 684.284 c
38.185 684.284 37.741 684.100 37.425 683.784 c
37.109 683.468 36.925 683.024 36.925 682.577 c
36.925 682.131 37.109 681.687 37.425 681.371 c
37.741 681.055 38.185 680.871 38.631 680.871 c
39.078 680.871 39.522 681.055 39.838 681.371 c
40.154 681.687 40.337 682.131 40.337 682.577 c f
BT 45.750 679.610 Td /F1 9.8 Tf  [(Based on evaluation by EGAPP)] TJ ET
0.267 0.267 0.267 rg
BT 183.410 679.610 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 194.252 679.610 Td /F1 9.8 Tf  [(, because there is no referent technology, it is not possible to estimate the false positive )] TJ ET
BT 45.750 667.705 Td /F1 9.8 Tf  [(or false negative rates of the test. Based on seven studies, testing initially failed in 14.5% of samples due to insufficient )] TJ ET
BT 45.750 655.800 Td /F1 9.8 Tf  [(tumor content, poor RNA samples, and RT-PCR failure. However, no studies have been conducted in node-positive breast )] TJ ET
BT 45.750 643.896 Td /F1 9.8 Tf  [(cancer patients.)] TJ ET
40.337 631.208 m 
40.337 631.655 40.154 632.099 39.838 632.415 c
39.522 632.731 39.078 632.915 38.631 632.915 c
38.185 632.915 37.741 632.731 37.425 632.415 c
37.109 632.099 36.925 631.655 36.925 631.208 c
36.925 630.762 37.109 630.318 37.425 630.002 c
37.741 629.686 38.185 629.502 38.631 629.502 c
39.078 629.502 39.522 629.686 39.838 630.002 c
40.154 630.318 40.337 630.762 40.337 631.208 c f
BT 45.750 628.241 Td /F1 9.8 Tf  [(Cronin et al.)] TJ ET
0.267 0.267 0.267 rg
BT 98.312 628.241 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 109.154 628.241 Td /F1 9.8 Tf  [(assessed the amplification efficiency, linearity, quantification limitations, dynamic range, analytical precision, )] TJ ET
BT 45.750 616.336 Td /F1 9.8 Tf  [(and reproducibility performance of Oncotype DX. The authors reported that the reproducibility of the recurrence score was )] TJ ET
BT 45.750 604.431 Td /F1 9.8 Tf  [(very high with repeat testing of de-identified patient samples \(standard deviation of less than 2 recurrence score units\).)] TJ ET
BT 26.250 581.277 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 581.277 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 581.277 Td /F1 9.8 Tf  [( test accuracy and reliability in predicting recurrence in node-positive breast cancer patients \(prognosis\) and )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(benefit from chemotherapy \(predictive\).)] TJ ET
40.337 552.935 m 
40.337 553.381 40.154 553.825 39.838 554.141 c
39.522 554.457 39.078 554.641 38.631 554.641 c
38.185 554.641 37.741 554.457 37.425 554.141 c
37.109 553.825 36.925 553.381 36.925 552.935 c
36.925 552.488 37.109 552.044 37.425 551.728 c
37.741 551.412 38.185 551.228 38.631 551.228 c
39.078 551.228 39.522 551.412 39.838 551.728 c
40.154 552.044 40.337 552.488 40.337 552.935 c f
BT 45.750 549.967 Td /F1 9.8 Tf  [(Retrospective analysis of the phase 3 trial SWOG-8814 reported on the clinical validity of Oncotype DX)] TJ ET
BT 489.560 553.855 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 502.075 549.967 Td /F1 9.8 Tf  [(in women who )] TJ ET
BT 45.750 538.062 Td /F1 9.8 Tf  [(had node-positive breast cancer and were treated with tamoxifen alone)] TJ ET
0.267 0.267 0.267 rg
BT 351.939 538.062 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 362.781 538.062 Td /F1 9.8 Tf  [(. The authors state that the study suggests that )] TJ ET
BT 45.750 526.158 Td /F1 9.8 Tf  [(patients with node-positive breast cancer with a low recurrence score do not seem to benefit from adjuvant chemotherapy )] TJ ET
BT 45.750 514.253 Td /F1 9.8 Tf  [(\(hazard ratio [HR]=1.02, 95% confidence interval [CI] = 0.54-1.93\), whereas those with a high recurrence score show an )] TJ ET
BT 45.750 502.348 Td /F1 9.8 Tf  [(improvement in disease-free survival, independent of the number of positive nodes \(HR=0.59, 95% CI = 0.35-1.01\). The RS )] TJ ET
BT 45.750 490.443 Td /F1 9.8 Tf  [(was also prognostic in the tamoxifen-alone group \(HR=2.64, 95% CI � 1.33 -5.27, for a 50-point difference in RS\).)] TJ ET
40.337 477.756 m 
40.337 478.203 40.154 478.647 39.838 478.963 c
39.522 479.279 39.078 479.462 38.631 479.462 c
38.185 479.462 37.741 479.279 37.425 478.963 c
37.109 478.647 36.925 478.203 36.925 477.756 c
36.925 477.310 37.109 476.866 37.425 476.550 c
37.741 476.234 38.185 476.050 38.631 476.050 c
39.078 476.050 39.522 476.234 39.838 476.550 c
40.154 476.866 40.337 477.310 40.337 477.756 c f
BT 45.750 474.789 Td /F1 9.8 Tf  [(Dowsett et al.)] TJ ET
0.267 0.267 0.267 rg
BT 104.816 474.789 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
BT 115.657 474.789 Td /F1 9.8 Tf  [(evaluated whether the recurrence score based on Oncotype DX provided independent information on risk )] TJ ET
BT 45.750 462.884 Td /F1 9.8 Tf  [(of distant recurrence in the tamoxifen and anastrozole arms of the ATAC Trial. The authors reported that recurrence score )] TJ ET
BT 45.750 450.979 Td /F1 9.8 Tf  [(is an independent prognosticator of recurrence in node-positive \(as well as node-negative\) breast cancer patients )] TJ ET
BT 45.750 439.074 Td /F1 9.8 Tf  [(\(HR=3.47, 95% CI = 1.64-7.38, for a 50-point difference in RS\) and concluded that it provides additional information to risk )] TJ ET
BT 45.750 427.170 Td /F1 9.8 Tf  [(determined using standard clinicopathologic features.)] TJ ET
BT 26.250 404.015 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
BT 90.727 404.015 Td /F4 9.8 Tf  [( : )] TJ ET
BT 99.394 404.015 Td /F1 9.8 Tf  [( net benefit of test in improving health outcomes.)] TJ ET
40.337 387.578 m 
40.337 388.024 40.154 388.468 39.838 388.784 c
39.522 389.100 39.078 389.284 38.631 389.284 c
38.185 389.284 37.741 389.100 37.425 388.784 c
37.109 388.468 36.925 388.024 36.925 387.578 c
36.925 387.131 37.109 386.687 37.425 386.371 c
37.741 386.055 38.185 385.872 38.631 385.872 c
39.078 385.872 39.522 386.055 39.838 386.371 c
40.154 386.687 40.337 387.131 40.337 387.578 c f
BT 45.750 384.610 Td /F1 9.8 Tf  [(No prospective studies assessing clinical utility have been conducted in women with node-positive breast cancer.)] TJ ET
40.337 371.923 m 
40.337 372.370 40.154 372.814 39.838 373.130 c
39.522 373.445 39.078 373.629 38.631 373.629 c
38.185 373.629 37.741 373.445 37.425 373.130 c
37.109 372.814 36.925 372.370 36.925 371.923 c
36.925 371.476 37.109 371.032 37.425 370.716 c
37.741 370.401 38.185 370.217 38.631 370.217 c
39.078 370.217 39.522 370.401 39.838 370.716 c
40.154 371.032 40.337 371.476 40.337 371.923 c f
BT 45.750 368.955 Td /F1 9.8 Tf  [(It is not clear whether recurrence scores for women with lymph-node positive breast cancer derived by the use of Oncotype )] TJ ET
BT 45.750 357.051 Td /F1 9.8 Tf  [(DX improves health outcome beyond current standard clinical classification methods)] TJ ET
0.267 0.267 0.267 rg
BT 409.347 357.051 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 420.189 357.051 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 344.364 m 
40.337 344.810 40.154 345.254 39.838 345.570 c
39.522 345.886 39.078 346.070 38.631 346.070 c
38.185 346.070 37.741 345.886 37.425 345.570 c
37.109 345.254 36.925 344.810 36.925 344.364 c
36.925 343.917 37.109 343.473 37.425 343.157 c
37.741 342.841 38.185 342.657 38.631 342.657 c
39.078 342.657 39.522 342.841 39.838 343.157 c
40.154 343.473 40.337 343.917 40.337 344.364 c f
BT 45.750 341.396 Td /F1 9.8 Tf  [(SWOG S-1007, a prospective, randomized trial to determine the effect of chemotherapy in patients with 1-3 positive nodes, )] TJ ET
BT 45.750 329.491 Td /F1 9.8 Tf  [(and hormone receptor-positive, HER2-negative breast cancer who do not have high RS by Oncotype DX. This trial, which )] TJ ET
BT 45.750 317.586 Td /F1 9.8 Tf  [(is scheduled to be completed in 2016 will provide evidence regarding the clinical utility of Oncotype DX)] TJ ET
0.267 0.267 0.267 rg
BT 487.942 317.586 Td /F1 9.8 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 498.784 317.586 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 294.432 Td /F4 9.8 Tf  [(Limitations)] TJ ET
40.337 277.995 m 
40.337 278.441 40.154 278.885 39.838 279.201 c
39.522 279.517 39.078 279.701 38.631 279.701 c
38.185 279.701 37.741 279.517 37.425 279.201 c
37.109 278.885 36.925 278.441 36.925 277.995 c
36.925 277.548 37.109 277.104 37.425 276.788 c
37.741 276.472 38.185 276.288 38.631 276.288 c
39.078 276.288 39.522 276.472 39.838 276.788 c
40.154 277.104 40.337 277.548 40.337 277.995 c f
BT 45.750 275.027 Td /F1 9.8 Tf  [(There is currently no data clearly demonstrating clinical utility of Oncotype DX in women with lymph node-positive breast )] TJ ET
BT 45.750 263.122 Td /F1 9.8 Tf  [(cancer.)] TJ ET
BT 26.250 222.770 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 202.815 Td /F1 9.8 Tf  [(Recently, gene expression marker panels that may better predict risk of breast cancer recurrence have become commercially )] TJ ET
BT 26.250 190.911 Td /F1 9.8 Tf  [(available and are being used to guide treatment decisions in women with node-negative breast cancer. This has led to one )] TJ ET
BT 26.250 179.006 Td /F1 9.8 Tf  [(prospective, randomized controlled study specifically focused on women with lymph node-positive breast cancer to assess )] TJ ET
BT 26.250 167.101 Td /F1 9.8 Tf  [(whether those panels can better predict recurrence in those patients as well. Although there is some evidence to suggest that )] TJ ET
BT 26.250 155.196 Td /F1 9.8 Tf  [(the use of Oncotype DX can provide additional information in predicting recurrence in women with lymph node-positive breast )] TJ ET
BT 26.250 143.292 Td /F1 9.8 Tf  [(cancer, there are currently no data from prospective clinical trials assessing the relative clinical benefit of OncotypeDX-guided )] TJ ET
BT 26.250 131.387 Td /F1 9.8 Tf  [(therapy vs. current care in those women. Therefore, it is unclear whether results of the gene expression panel can be used to )] TJ ET
BT 26.250 119.482 Td /F1 9.8 Tf  [(withhold chemotherapy for a portion of women who otherwise would receive it as part of therapy. Thus, current data cannot )] TJ ET
BT 26.250 107.577 Td /F1 9.8 Tf  [(answer the question of whether Oncotype Dx-guided practice improves health outcomes beyond standard clinical practice.)] TJ ET
BT 26.250 88.173 Td /F4 9.8 Tf  [(Links)] TJ ET
BT 26.250 68.768 Td /F1 9.8 Tf  [(Last updated: July 21, 2011)] TJ ET
BT 26.250 49.363 Td /F4 9.8 Tf  [(Acknowledgements)] TJ ET
Q
q
15.000 39.482 577.500 737.518 re W n
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BT 26.250 767.476 Td /F1 9.8 Tf  [(breast cancer.)] TJ ET
BT 26.250 730.874 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 710.919 Td /F5 9.8 Tf  [(Analytical Validity)] TJ ET
BT 109.700 710.919 Td /F4 9.8 Tf  [( : )] TJ ET
BT 118.368 710.919 Td /F1 9.8 Tf  [( test accuracy and reliability in measuring differences in expression of relevant genes \(analytic sensitivity )] TJ ET
BT 26.250 699.015 Td /F1 9.8 Tf  [(and specificity\).)] TJ ET
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40.337 682.577 m 
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39.522 684.100 39.078 684.284 38.631 684.284 c
38.185 684.284 37.741 684.100 37.425 683.784 c
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36.925 682.131 37.109 681.687 37.425 681.371 c
37.741 681.055 38.185 680.871 38.631 680.871 c
39.078 680.871 39.522 681.055 39.838 681.371 c
40.154 681.687 40.337 682.131 40.337 682.577 c f
BT 45.750 679.610 Td /F1 9.8 Tf  [(Based on evaluation by EGAPP)] TJ ET
0.267 0.267 0.267 rg
BT 183.410 679.610 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 194.252 679.610 Td /F1 9.8 Tf  [(, because there is no referent technology, it is not possible to estimate the false positive )] TJ ET
BT 45.750 667.705 Td /F1 9.8 Tf  [(or false negative rates of the test. Based on seven studies, testing initially failed in 14.5% of samples due to insufficient )] TJ ET
BT 45.750 655.800 Td /F1 9.8 Tf  [(tumor content, poor RNA samples, and RT-PCR failure. However, no studies have been conducted in node-positive breast )] TJ ET
BT 45.750 643.896 Td /F1 9.8 Tf  [(cancer patients.)] TJ ET
40.337 631.208 m 
40.337 631.655 40.154 632.099 39.838 632.415 c
39.522 632.731 39.078 632.915 38.631 632.915 c
38.185 632.915 37.741 632.731 37.425 632.415 c
37.109 632.099 36.925 631.655 36.925 631.208 c
36.925 630.762 37.109 630.318 37.425 630.002 c
37.741 629.686 38.185 629.502 38.631 629.502 c
39.078 629.502 39.522 629.686 39.838 630.002 c
40.154 630.318 40.337 630.762 40.337 631.208 c f
BT 45.750 628.241 Td /F1 9.8 Tf  [(Cronin et al.)] TJ ET
0.267 0.267 0.267 rg
BT 98.312 628.241 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 109.154 628.241 Td /F1 9.8 Tf  [(assessed the amplification efficiency, linearity, quantification limitations, dynamic range, analytical precision, )] TJ ET
BT 45.750 616.336 Td /F1 9.8 Tf  [(and reproducibility performance of Oncotype DX. The authors reported that the reproducibility of the recurrence score was )] TJ ET
BT 45.750 604.431 Td /F1 9.8 Tf  [(very high with repeat testing of de-identified patient samples \(standard deviation of less than 2 recurrence score units\).)] TJ ET
BT 26.250 581.277 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
BT 98.322 581.277 Td /F4 9.8 Tf  [( : )] TJ ET
BT 106.990 581.277 Td /F1 9.8 Tf  [( test accuracy and reliability in predicting recurrence in node-positive breast cancer patients \(prognosis\) and )] TJ ET
BT 26.250 569.372 Td /F1 9.8 Tf  [(benefit from chemotherapy \(predictive\).)] TJ ET
40.337 552.935 m 
40.337 553.381 40.154 553.825 39.838 554.141 c
39.522 554.457 39.078 554.641 38.631 554.641 c
38.185 554.641 37.741 554.457 37.425 554.141 c
37.109 553.825 36.925 553.381 36.925 552.935 c
36.925 552.488 37.109 552.044 37.425 551.728 c
37.741 551.412 38.185 551.228 38.631 551.228 c
39.078 551.228 39.522 551.412 39.838 551.728 c
40.154 552.044 40.337 552.488 40.337 552.935 c f
BT 45.750 549.967 Td /F1 9.8 Tf  [(Retrospective analysis of the phase 3 trial SWOG-8814 reported on the clinical validity of Oncotype DX)] TJ ET
BT 489.560 553.855 Td /F1 8.7 Tf  [(TM)] TJ ET
BT 502.075 549.967 Td /F1 9.8 Tf  [(in women who )] TJ ET
BT 45.750 538.062 Td /F1 9.8 Tf  [(had node-positive breast cancer and were treated with tamoxifen alone)] TJ ET
0.267 0.267 0.267 rg
BT 351.939 538.062 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 362.781 538.062 Td /F1 9.8 Tf  [(. The authors state that the study suggests that )] TJ ET
BT 45.750 526.158 Td /F1 9.8 Tf  [(patients with node-positive breast cancer with a low recurrence score do not seem to benefit from adjuvant chemotherapy )] TJ ET
BT 45.750 514.253 Td /F1 9.8 Tf  [(\(hazard ratio [HR]=1.02, 95% confidence interval [CI] = 0.54-1.93\), whereas those with a high recurrence score show an )] TJ ET
BT 45.750 502.348 Td /F1 9.8 Tf  [(improvement in disease-free survival, independent of the number of positive nodes \(HR=0.59, 95% CI = 0.35-1.01\). The RS )] TJ ET
BT 45.750 490.443 Td /F1 9.8 Tf  [(was also prognostic in the tamoxifen-alone group \(HR=2.64, 95% CI � 1.33 -5.27, for a 50-point difference in RS\).)] TJ ET
40.337 477.756 m 
40.337 478.203 40.154 478.647 39.838 478.963 c
39.522 479.279 39.078 479.462 38.631 479.462 c
38.185 479.462 37.741 479.279 37.425 478.963 c
37.109 478.647 36.925 478.203 36.925 477.756 c
36.925 477.310 37.109 476.866 37.425 476.550 c
37.741 476.234 38.185 476.050 38.631 476.050 c
39.078 476.050 39.522 476.234 39.838 476.550 c
40.154 476.866 40.337 477.310 40.337 477.756 c f
BT 45.750 474.789 Td /F1 9.8 Tf  [(Dowsett et al.)] TJ ET
0.267 0.267 0.267 rg
BT 104.816 474.789 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
BT 115.657 474.789 Td /F1 9.8 Tf  [(evaluated whether the recurrence score based on Oncotype DX provided independent information on risk )] TJ ET
BT 45.750 462.884 Td /F1 9.8 Tf  [(of distant recurrence in the tamoxifen and anastrozole arms of the ATAC Trial. The authors reported that recurrence score )] TJ ET
BT 45.750 450.979 Td /F1 9.8 Tf  [(is an independent prognosticator of recurrence in node-positive \(as well as node-negative\) breast cancer patients )] TJ ET
BT 45.750 439.074 Td /F1 9.8 Tf  [(\(HR=3.47, 95% CI = 1.64-7.38, for a 50-point difference in RS\) and concluded that it provides additional information to risk )] TJ ET
BT 45.750 427.170 Td /F1 9.8 Tf  [(determined using standard clinicopathologic features.)] TJ ET
BT 26.250 404.015 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
BT 90.727 404.015 Td /F4 9.8 Tf  [( : )] TJ ET
BT 99.394 404.015 Td /F1 9.8 Tf  [( net benefit of test in improving health outcomes.)] TJ ET
40.337 387.578 m 
40.337 388.024 40.154 388.468 39.838 388.784 c
39.522 389.100 39.078 389.284 38.631 389.284 c
38.185 389.284 37.741 389.100 37.425 388.784 c
37.109 388.468 36.925 388.024 36.925 387.578 c
36.925 387.131 37.109 386.687 37.425 386.371 c
37.741 386.055 38.185 385.872 38.631 385.872 c
39.078 385.872 39.522 386.055 39.838 386.371 c
40.154 386.687 40.337 387.131 40.337 387.578 c f
BT 45.750 384.610 Td /F1 9.8 Tf  [(No prospective studies assessing clinical utility have been conducted in women with node-positive breast cancer.)] TJ ET
40.337 371.923 m 
40.337 372.370 40.154 372.814 39.838 373.130 c
39.522 373.445 39.078 373.629 38.631 373.629 c
38.185 373.629 37.741 373.445 37.425 373.130 c
37.109 372.814 36.925 372.370 36.925 371.923 c
36.925 371.476 37.109 371.032 37.425 370.716 c
37.741 370.401 38.185 370.217 38.631 370.217 c
39.078 370.217 39.522 370.401 39.838 370.716 c
40.154 371.032 40.337 371.476 40.337 371.923 c f
BT 45.750 368.955 Td /F1 9.8 Tf  [(It is not clear whether recurrence scores for women with lymph-node positive breast cancer derived by the use of Oncotype )] TJ ET
BT 45.750 357.051 Td /F1 9.8 Tf  [(DX improves health outcome beyond current standard clinical classification methods)] TJ ET
0.267 0.267 0.267 rg
BT 409.347 357.051 Td /F1 9.8 Tf  [([3])] TJ ET
0.271 0.267 0.267 rg
BT 420.189 357.051 Td /F1 9.8 Tf  [(.)] TJ ET
40.337 344.364 m 
40.337 344.810 40.154 345.254 39.838 345.570 c
39.522 345.886 39.078 346.070 38.631 346.070 c
38.185 346.070 37.741 345.886 37.425 345.570 c
37.109 345.254 36.925 344.810 36.925 344.364 c
36.925 343.917 37.109 343.473 37.425 343.157 c
37.741 342.841 38.185 342.657 38.631 342.657 c
39.078 342.657 39.522 342.841 39.838 343.157 c
40.154 343.473 40.337 343.917 40.337 344.364 c f
BT 45.750 341.396 Td /F1 9.8 Tf  [(SWOG S-1007, a prospective, randomized trial to determine the effect of chemotherapy in patients with 1-3 positive nodes, )] TJ ET
BT 45.750 329.491 Td /F1 9.8 Tf  [(and hormone receptor-positive, HER2-negative breast cancer who do not have high RS by Oncotype DX. This trial, which )] TJ ET
BT 45.750 317.586 Td /F1 9.8 Tf  [(is scheduled to be completed in 2016 will provide evidence regarding the clinical utility of Oncotype DX)] TJ ET
0.267 0.267 0.267 rg
BT 487.942 317.586 Td /F1 9.8 Tf  [([8])] TJ ET
0.271 0.267 0.267 rg
BT 498.784 317.586 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 294.432 Td /F4 9.8 Tf  [(Limitations)] TJ ET
40.337 277.995 m 
40.337 278.441 40.154 278.885 39.838 279.201 c
39.522 279.517 39.078 279.701 38.631 279.701 c
38.185 279.701 37.741 279.517 37.425 279.201 c
37.109 278.885 36.925 278.441 36.925 277.995 c
36.925 277.548 37.109 277.104 37.425 276.788 c
37.741 276.472 38.185 276.288 38.631 276.288 c
39.078 276.288 39.522 276.472 39.838 276.788 c
40.154 277.104 40.337 277.548 40.337 277.995 c f
BT 45.750 275.027 Td /F1 9.8 Tf  [(There is currently no data clearly demonstrating clinical utility of Oncotype DX in women with lymph node-positive breast )] TJ ET
BT 45.750 263.122 Td /F1 9.8 Tf  [(cancer.)] TJ ET
BT 26.250 222.770 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 202.815 Td /F1 9.8 Tf  [(Recently, gene expression marker panels that may better predict risk of breast cancer recurrence have become commercially )] TJ ET
BT 26.250 190.911 Td /F1 9.8 Tf  [(available and are being used to guide treatment decisions in women with node-negative breast cancer. This has led to one )] TJ ET
BT 26.250 179.006 Td /F1 9.8 Tf  [(prospective, randomized controlled study specifically focused on women with lymph node-positive breast cancer to assess )] TJ ET
BT 26.250 167.101 Td /F1 9.8 Tf  [(whether those panels can better predict recurrence in those patients as well. Although there is some evidence to suggest that )] TJ ET
BT 26.250 155.196 Td /F1 9.8 Tf  [(the use of Oncotype DX can provide additional information in predicting recurrence in women with lymph node-positive breast )] TJ ET
BT 26.250 143.292 Td /F1 9.8 Tf  [(cancer, there are currently no data from prospective clinical trials assessing the relative clinical benefit of OncotypeDX-guided )] TJ ET
BT 26.250 131.387 Td /F1 9.8 Tf  [(therapy vs. current care in those women. Therefore, it is unclear whether results of the gene expression panel can be used to )] TJ ET
BT 26.250 119.482 Td /F1 9.8 Tf  [(withhold chemotherapy for a portion of women who otherwise would receive it as part of therapy. Thus, current data cannot )] TJ ET
BT 26.250 107.577 Td /F1 9.8 Tf  [(answer the question of whether Oncotype Dx-guided practice improves health outcomes beyond standard clinical practice.)] TJ ET
BT 26.250 88.173 Td /F4 9.8 Tf  [(Links)] TJ ET
BT 26.250 68.768 Td /F1 9.8 Tf  [(Last updated: July 21, 2011)] TJ ET
BT 26.250 49.363 Td /F4 9.8 Tf  [(Acknowledgements)] TJ ET
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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

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BT 26.250 767.476 Td /F1 9.8 Tf  [(The authors would like to thank Dr. Muin Khoury of the Centers for Disease Control and Prevention and Dr. David Veenstra of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(the University of Washington for their invaluable input and guidance on the content. The authors also acknowledge the )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(contributions of Ms. Camilla Benedicto and Ms. Kelly Bennett of the National Cancer Institute in supporting this project.)] TJ ET
BT 26.250 724.262 Td /F4 9.8 Tf  [(Funding information)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(This study was funded, in part, by CANCERGEN \(Comparative Effectiveness Research in Cancer Genomics\) through the )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(American Recovery and Reinvestment Act of 2009 by the National Cancer Institute, National Institutes of Health under Agency )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Award #RC2CA138570 \(Principal Investigator: Scott D. Ramsey\).)] TJ ET
BT 26.250 661.643 Td /F4 9.8 Tf  [(Competing interests)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(The authors have declared no competing interests exist.)] TJ ET
BT 26.250 622.833 Td /F4 9.8 Tf  [(Disclaimers)] TJ ET
BT 26.250 603.429 Td /F1 9.8 Tf  [(The findings and conclusions are those of the authors and do not necessarily represent the views of the National Institutes of )] TJ ET
BT 26.250 591.524 Td /F1 9.8 Tf  [(Health \(NIH\). The information provided in this manuscript does not constitute an endorsement of Oncotype DX by NIH nor the )] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(Department of Health and Human Services of the U.S. government.)] TJ ET
BT 26.250 543.017 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 515.562 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 515.562 Td /F1 9.8 Tf  [(https://ww2.cancer.org/downloads/STT/Cancer_Facts_Figures_2010.pdf)] TJ ET
0.267 0.267 0.267 rg
BT 26.250 507.077 Td /F1 7.5 Tf  [(REFERENCE LINK)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 488.526 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 488.526 Td /F1 9.8 Tf  [(Gene expression profiling of breast cancer to select women for adjuvant chemotherapy. Technol Eval Cent Asses Program )] TJ ET
BT 26.250 476.622 Td /F1 9.8 Tf  [(Exec Summ. 2008 Apr;22\(13\):1-8. PubMed PMID: 18663816.)] TJ ET
BT 26.250 457.217 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 457.217 Td /F1 9.8 Tf  [(https://www.bcbs.com/blueresources/tec/vols/25/25_01.pdf)] TJ ET
0.267 0.267 0.267 rg
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