1. The 12-gene DCIS Score Assay and Quantitative Gene Expression for ER, PR, and HER2: Experience with 3,947 Patients Alvarado MD, 1 Tan V, 2 Bailey H, 2 Anderson J, 2 Rothney M, 2 Baehner FL, 1-2 Sing AP 2 1 Department of Pathology, University of California, San Francisco, CA ; 2 Genomic Health, Inc., Redwood City, CA Objective: To examine the quantitative expression of the estrogen receptor (ER), progesterone receptor (PR), Her-2/neu receptor (HER2), and DCIS Score™ result across clinicopathologic variables (patient age, specimen type, DCIS subtypes) from submitted patient samples tested in the Genomic Health laboratory Methods: A total of 3,947 patient samples from December 2011 through June 2014 that passed pathology review and RT-PCR quality measures were included. The Oncotype DX® assay for DCIS is the first molecular assay that gives additional independent and individualized estimates of 10-year risk of any local recurrence (LR) and invasive LR. Solin JNCI 2013

2. The distribution of DCIS Score groups (n=3,947) was similar to the distribution observed within the ECOG 5194 validation study Risk GroupNPercentE5194 Study DCIS Score <39 (Low)266067.4%70.3% DCIS Score 39-54 (Intermediate)68217.3%16.2% DCIS Score ≥55 (High)60515.3%13.5% Solin JNCI 2013

3. DCIS Score Result, ER, PR and HER2 by Tumor Type 3 There was a wide range of mean values for DCIS Score result and single gene expression across tumor types. Mean Tumor TypeN(%)DCIS Score (range) ERPRHER2 Cribriform1575 (39.9%) 22 (0-90) 10.07.89.8 Solid1371 (34.7%) 34 (0-100) 9.57.29.9 Comedonecrosis462 (11.7%) 47 (0-100) 8.46.310.3 Papillary334 (8.5%) 17 (0-90) 10.98.69.6 Micropapillary183 (4.6%) 25 (0-88) 9.47.310.0 Apocrine12 (0.3%)27 (4-53) 7.46.09.9 ER: ≥6.5 positive; PR: ≥5.5 positive; HER2: ≥11.5 positive, 10.7-11.4 equivocal, <10.7 negative 0.3% were classified as DCIS, not otherwise specified

4. Correlation Pattern of Single Gene Expression The majority of samples (81.2%) were ER- and PR-positive. Very few (approximately 1%) of DCIS cases were found to be ER-negative and PR-positive. Approximately 8.9% of samples were ER-negative and 3.3% were both ER-negative and HER2- negative. The majority of samples (78.4%) were ER-positive and HER2-negative. A total of 8.4% of DCIS cases were ER-positive with concurrent elevated levels of HER2 expression. ER by PR ER by HER2 ER PR HER2