<p> Breast Cancer Research and Treatment</p><p>TOP2A RNA Expression and Recurrence in Estrogen Receptor-Positive Breast Cancer </p><p>Joseph A. Sparano, Lori J. Goldstein, Nancy E. Davidson, George W. Sledge, Jr., and Robert Gray5</p><p>Corresponding author: Joseph A. Sparano, MD, Montefiore-Einstein Cancer Center, Montefiore Medical Center-Weiler Division, 1825 Eastchester Rd. Bronx, NY 10461; Phone 718-904-2555; Fax 718-904-2892; Email: [email protected]</p><p>Supplemental Tables 1-4</p><p>Supplemental Table 1. Cutoffs and number of positive cases/total cases for Her2, ER and PgR ERBB2 ESR1 PGR # HR+, HER2- cases (# events) Wang et al 12.8 (51/286) 10.0 (207/286) 4.6 (151/286) 192 (73) Van de Vijver 0.0 (53/295) -0.65 (226/295) -0.40 (226/295) 212 (68) et al Desmedt et al 7.7 (39/198) 10.0 (136/198) 4.6 (125/198) 124 (33) Loi et al 0.8 (39/263) -- -- 224 (70) Supplemental Table 2. Estimated hazard ratios and 95% confidence intervals for TOP2A and simRS.</p><p>Data Set Model Effect Estimated 95% Confidence P-value</p><p>Ratio Intervals Wang et al simRS simRs 1.69 (1.38, 2.08) <0.0001 TOP2A TOP2A 1.58 (1.21, 2.05) 0.001 TOP2A + simRS TOP2A 1.2 (0.90, 1.61) 0.21 TOP2A + simRS simRS 1.54 (1.20, 1.98) 0.0007</p><p>Van de Sim RS simRS 1.7 (1.41, 2.04) <0.0001 Vijver et al TOP2A TOP2A 1.62 (1.27,2.07) 0.0001 TOP2A + simRS TOP2A 1.3 (0.99,1.69) 0.06 TOP2A + simRS simRS 1.55 (1.26, 1.92) <0.0001</p><p>Desmedt et simRS simRS 1.49 (1.13, 1.96) 0.004 al TOP2A TOP2A 1.83 (1.27, 2.64) 0.001 TOP2A+simRS TOP2A 1.63 (1.09, 2.44) 0.02 TOP2A+simRS simRS 1.23 (0.90, 1.67) 0.2</p><p>Loi et al simRS simRS 1.49 (1.22, 1.81) 0.0001 TOP2A TOP2A 1.41 (1.11, 1.78) 0.004 TOP2A+simRS TOP2A 1.15 (0.87, 1.52) 0.33 TOP2A+simRS simRS 1.37 (1.07, 1.77) 0.01</p><p>Supplemental Table 3. Five-year relapse free survival by high vs. low TOP2A (overall median split) within classical RS risk groups, with logrank p-values for the TOP2A comparison in each group Low TOP2A High TOP2A Classical SimRS Data Set Group No. 5-yr RFS SE No. 5-yr RFS SE P Value</p><p>Wang et al Low 61 78.6 5.3 29 79.3 7.5 0.99 Intermediate 31 87.1 6 34 49.5 8.6 0.02 High 4 25 21.7 33 39.4 8.5 0.19</p><p>Vijver et al Low 62 93.4 3.2 38 83.5 6.2 0.41 Intermediate 34 79.4 6.9 37 69.5 7.7 0.88 High 10 40 15.5 31 47 9.1 0.61</p><p>Desmedt et al Low 37 80.8 6.5 21 85.7 7.6 0.61 Intermediate 23 86.3 7.4 19 57.9 11.3 0.03 High 2 50 35.4 22 50 10.7 0.85</p><p>Loi et al Low 73 83.8 4.5 32 81.8 7.4 0.2 Intermediate 32 86.7 6.2 44 80.1 6.3 0.24 High 7 42.9 18.7 36 56.2 9 0.46 Abbreviations: RFS – relapse free survival; SE – standard error Note: RS groups use the proportions from the E2197 HR-positive, HER2- negative subset (47% low <18, 34%, intermediate 18-30, 19% high > 30). Supplemental Table 4. Five-year relapse free survival by high vs. low TOP2A (overall median split) within TAILORx RS risk groups, with logrank p-values for the TOP2A comparison in each group</p><p>Low High TOP2A TOP2A Data Set TAILORx No. 5-yr RFS SE No. 5-yr RFS SE simRS Group</p><p>Wang et al Low 20 79.3 9.2 13 92.3 7.4 0.68 Intermedia te 67 83.6 4.5 36 60.9 8.2 0.04 High 9 44.4 16.6 47 40.1 7.2 0.54</p><p>Van de P Value Vijver et al Low 24 100 0 12 73.3 13.2 0.05 Intermedia te 66 86 4.3 48 85 5.2 0.62 High 16 50 12.5 46 48 7.5 0.97</p><p>Desmedt et al Low 11 90.9 8.7 10 90 9.5 0.92 Intermedia te 45 79.4 6.1 22 72.7 9.5 0.62 High 6 83.3 15.2 30 50 9.1 0.15</p><p>Loi et al Low 30 81.6 7.4 8 100 0 0.22 Intermedia te 65 85.4 4.5 56 78.2 5.9 0.16 High 17 70.6 11.1 48 63.4 7.4 0.24 Abbrevia tions: RFS – relapse free survival; S.E. – standard error Note: TAILORx RS groups use the proportions from the E2197 HR-positive, HER2-negative subset (17% low <11, 54%, intermediate 11-25, 29% high > 25) </p>