Oncotype DX reveals the underlying biology that changes treatment decisions 37% of the time

Oncotype DX reveals the underlying biology that changes treatment decisions 37% of the time Even when treatment decisions based on traditional measures seem conclusive, Oncotype DX can lead to a different approach For newly diagnosed patients with node-negative or node-positive, ER-positive, HER2-negative invasive breast cancer Uncover the Unexpected TM

The Oncotype DX Breast Cancer Assay results change treatment decisions Individualized Recurrence Score (RS) results assess the potential benefit of chemotherapy and the likelihood of distant breast cancer recurrence Treatment decisions were changed even when definitive treatment decisions had already been made for these patients* 1 33% of the overall population switched from CT + HT to HT alone based on a low Recurrence Score result 4% of the overall population switched from HT only to CT + HT based on a high Recurrence Score result Treatment decisions* 1 37% changed 63% confirmed *This analysis included 912 patients with node-negative, ER-positive early-stage invasive breast cancer. Patients with unclear treatment decisions were excluded from this meta-analysis. Additionally, patients who did not want CT, those with poor performance status, and those who could not tolerate CT were excluded. CT=chemotherapy; HT=hormone therapy. Before RS After RS The Oncotype DX assay consistently changed treatment decisions across 7 independent studies 2-8 CT + HT HT (n=297) HT HT (n=303) CT + HT CT + HT (n=271) HT CT + HT (n=41) (TOTAL=912) (n=600) (n=312) Asad et al 2 (n=81) 36 13 24 8 Henry et al 3 (n=29) 7 14 6 2 Klang et al 4 (n=313) 105 119 69 20 Liang et al 5 (n=260) 85 47 125 3 Lo et al 6 (n=83) 20 40 20 3 Oratz et al 7 (n=68) 14 32 19 3 Thanasoulis et al 8 (n=78) 30 38 8 2 % with changed treatment decisions 33% 4% All studies except Henry et al had statistically significant differences in CT recommendation before and after Recurrence Score testing. Studies have shown that Recurrence Score results reduce chemotherapy use, spare patients the negative health and quality of life impact of unnecessary chemotherapy, and reduce the costs to society and the healthcare system 1,6,9,10 2

Oncotype DX is the only multigene breast cancer assay incorporated into 3 major clinical guidelines Clinical practice guidelines 11-13 NCCN Guidelines 11 ASCO Guidelines 12 St Gallen Consensus Guidelines 13 Consider use in >0.5 cm, HR+, HER2-negative disease pt1, pt2, or pt3; and pn0 or pn1mi ( 2 mm axillary node metastasis) Newly diagnosed patients with node-negative, ER+ breast cancer who will receive tamoxifen Oncotype DX has been shown to predict chemotherapy benefit among patients with HR+ disease The only multigene breast cancer assay based on NCI* Level 1, Category B evidence 14 *National Cancer Institute. The Oncotype DX assay analyzes the expression of 21 genes to provide a Recurrence Score unique to each patient 15,16 The Recurrence Score predicts chemotherapy benefit and indicates the 10-year risk of distant recurrence The Oncotype DX assay provides an individualized Recurrence Score result The Recurrence Score reflects an individual s unique tumor biology 15-17 Rate of distant recurrence at 10 years 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% LOW RISK Group Average: 7% 95% CI: 4% 20% INTERMEDIATE RISK Group Average: 14% 95% CI: 8% 20% HIGH RISK Group Average: 31% 95% CI: 24% 37% Rate 95% CI Patient as compared to clinical trial population High Recurrence Score disease: Aggressive Less sensitive to hormone therapy Large chemotherapy benefit 0% 0 5 10 15 20 25 30 35 40 45 50 100 Low Recurrence Score disease: Indolent Hormone therapy sensitive Minimal, if any, chemotherapy benefit Recurrence Score Result For Recurrence Score >50, group average rate of distant recurrence and 95% CI shown. 3

Patient age and tumor size cannot predict the Recurrence Score result The Oncotype DX assay Recurrence Score results provide additional insight into underlying tumor biology 15 NSABP B-20 trial (n=651) 15 Recurrence Score 100 80 60 40 20 0 41% 14% 44% <40 (n=63) 24% 21% 55% 40 49 (n=226) 28% 22% 50% 50 59 (n=166) 19% 21% 60% 60 (n=196) Recurrence Score result <18 18 30 31 Younger patients can have low Recurrence Score results Patient age (years) Older patients can have high Recurrence Score results NSABP B-20 trial (n=651) 15 Recurrence Score 100 80 60 40 20 0 16% 20% 64% 1 (n=110) 25% 19% 56% 1.1 2 (n=318) 30% 23% 46% 2.1 4 (n=196) 33% 21% 46% >4 (n=24) Recurrence Score result <18 18 30 31 Patients with small tumors can have high Recurrence Score results Clinical tumor size (cm) Patients with large tumors can have low Recurrence Score results 4

Tumor grade cannot predict the Recurrence Score result The Oncotype DX assay reveals critical information that changes treatment decisions 15 NSABP B-20 trial (n=651) 15 Recurrence Score 100 80 60 40 20 0 12% 16% 73% WELL (n=77) GRADING BY PATHOLOGIST AT LOCAL HOSPITAL 22% 22% 56% MODERATE (n=339) 42% 22% 36% POOR (n=163) Recurrence Score result <18 18 30 31 Tumor grade (site) Even low-grade tumors can have high Recurrence Score results Significant proportions of high-grade tumors have low Recurrence Score results 100 GRADING BY PATHOLOGIST AT CENTRAL LAB Recurrence Score 80 60 40 20 0 5% 12% 83% WELL (n=119) 12% 24% 64% MODERATE (n=340) 61% 19% 19% POOR (n=190) Tumor grade (central) Because high and low Oncotype DX Recurrence Score results reflect different intrinsic tumor biology, physicians can make decisions based on underlying disease 5

The Oncotype DX assay provides prognostic information for node-negative patients Prognostic*: The Recurrence Score (RS) result is directly correlated with the rate of distant recurrence 16 A low Recurrence Score result correlated with a lower rate of distant recurrence, while a high Recurrence Score result correlated with a higher rate of distant recurrence 16 NSABP B-14: 10-year rate of distant recurrence was significantly lower for patients with low Recurrence Score results 16 Rate of distant recurrence at 10 years (%) 35 30 25 20 15 10 5 0 6.8% 95% Cl 4% 9.6% LOW RISK RS <18 14.3% 95% Cl 8.3% 20.3% INTERMEDIATE RISK RS 18 30 30.5% 95% Cl 23.6% 37.4% HIGH RISK RS 31 CI=confidence interval. NSABP B-14: The majority of patients had low Recurrence Score results 16 51% RS <18 27% RS 31 22% RS 18 30 *Prognostic: Any measurement available at the time of diagnosis or surgery associated with clinical outcome in the absence of systematic adjuvant therapy or following the standard of care treatment. 6 NSABP B-14 Prospective analysis of archived tissue from 668 stage I or II patients with ER-positive, node-negative invasive breast cancer treated with tamoxifen. Twenty-nine percent of patients were <50 years of age and 62% had tumors that were 2.0 cm in size. The 10-year distant recurrence rate for the overall study population was 15%.

Only the Oncotype DX assay provides predictive information for node-negative patients Predictive*: The Recurrence Score is associated with the level of benefit from chemotherapy NSABP B-20: A high Recurrence Score result predicted a significant benefit from chemotherapy (n=651) 15 LOW RECURRENCE SCORE RESULT (<18) little to no chemotherapy benefit INTERMEDIATE RECURRENCE SCORE RESULT (18 30) no substantial chemotherapy benefit Proportion without distant recurrence 1.0 0.8 0.6 0.4 0.2 0.0 P=0.61 n Events Tam + chemo 218 8 Tam 135 4 0 2 4 6 8 10 12 Years 97% 96% Proportion without distant recurrence 1.0 0.8 0.6 0.4 0.2 0.0 P=0.39 n Events Tam + chemo 89 9 Tam 45 4 0 2 4 6 8 10 12 Years 91% 89% HIGH RECURRENCE SCORE RESULT ( 31) large chemotherapy benefit Proportion without distant recurrence 1.0 0.8 0.6 0.4 0.2 0.0 P<0.001 n Events Tam + chemo 117 13 Tam 47 18 0 2 4 6 8 10 12 Years 88% 60% 28% absolute benefit from Tam + chemo *Predictive: Any measurement associated with benefit or lack of benefit from a particular therapy. NSABP B-20 Prospective analysis of archived tissue from 651 patients with ER-positive, node-negative invasive breast cancer treated with tamoxifen or tamoxifen plus CMF/MF. Approximately 45% of the patients were <50 years of age, two-thirds of tumors were 2.0 cm in size, and 20% of tumors were PR-negative. 7

The Oncotype DX assay provides recurrence risk information for both node-negative and node-positive patients Trans ATAC: Recurrence risks seen in node-negative patients and patients with 1 3 positive nodes who had low Recurrence Score results (n=1,178) 18 9-year risk of distant recurrence (%) 100 90 80 70 60 50 40 30 20 10 4+ POSITIVE NODES n=63 (31 EVENTS) 1 3 POSITIVE NODES n=243 (43 EVENTS) NODE- NEGATIVE n=872 (72 EVENTS) Mean 95% Cl The risk of 9-year distant recurrence increased with the number of positive nodes and the Recurrence Score result For low Recurrence Score results, the risk of 9-year distant recurrence for node-negative patients and those with 1 3 positive nodes was similar 0 0 5 10 15 20 25 30 35 40 45 50 Recurrence Score 8 Trans ATAC Prospective analysis of archived tissue from 1,231 postmenopausal patients with invasive breast cancer treated with tamoxifen or an aromatase inhibitor, of whom 1,178 were ER-positive and either node-negative or node-positive. Of 306 node-positive patients: 79% had 1 3 positive nodes, 21% had 4 or more positive nodes, and 4% had unknown nodal status. The mean age was 64 years and 67% of tumors were 2.0 cm in size.

The Oncotype DX assay predicts the benefit of chemotherapy in node-positive patients SWOG 8814: Significant chemotherapy benefit only in the high Recurrence Score result group (n=367) 19 LOW RECURRENCE SCORE RESULT (<18) INTERMEDIATE RECURRENCE SCORE RESULT (18 30) Breast cancer specific survival 1.00 0.75 0.50 0.25 0.0 92% 87% P=0.56 n Events Tam only 55 4 CAF-T 91 10 0 2 4 6 8 10 Years Breast cancer specific survival 1.00 0.75 0.50 0.25 0.0 81% 70% P=0.89 n Events Tam only 46 11 CAF-T 57 10 0 2 4 6 8 10 Years No substantial benefit in breast cancer specific survival from anthracycline-based chemotherapy for node-positive patients with low Recurrence Score results Breast cancer specific survival 1.00 0.75 0.50 0.25 0.0 HIGH RECURRENCE SCORE RESULT ( 31) P=0.033 n Events 73% 54% Tam only 47 20 CAF-T 71 18 0 2 4 6 8 10 Years Substantial benefit in breast cancer specific survival from anthracycline-based chemotherapy for nodepositive patients with high Recurrence Score results SWOG 8814 Prospective analysis of archived tissue from 367 postmenopausal, hormone receptor positive, node-positive patients with invasive breast cancer treated with tamoxifen or tamoxifen plus CAF. Approximately 62% had 1 3 positive nodes and the remainder had 4 or more. Mean age was 60 years (range 42 81), 20% were PR-negative, and 64% of tumors were 2 5 cm in size. 9

21 genes reveal the underlying biology that provides prognostic and predictive information Genes responsible for generating the Recurrence Score (RS) result and report16 PROLIFERATION INVASION Ki-67 STK15 Survivin Cyclin B1 MYBL2 Stromelysin 3 Cathepsin L2 ESTROGEN OTHER ER PR Bcl-2 SCUBE2 GSTM1 CD68 BAG1 HER2 REFERENCE GRB7 HER2 Beta-actin GAPDH RPLPO GUS TFRC 16 cancer genes 5 reference genes RS = +0.47 x HER2 group score 0.34 x Estrogen group score +1.04 x Proliferation group score +0.10 x Invasion group score +0.05 x CD68 0.08 x GSTM1 0.07 x BAG1. Sample report PATIENT REPORT Patient/ID: Sex: DOB: Medical Record/Patient #: Date of Surgery: Specimen Type/ID: BREAST CANCER ASSAY DESCRIPTION E L type P RESULTS Breast Cancer = Recurrence Score PATIENT REPORT Requisition: Order Received: Date Reported: Client: Ordering Physician: Submitting Pathologist: Submitting Pathologist: 6 CLINICAL EXPERIENCE: PROGNOSIS FOR NODE NEGATIVE, ER-POSITIVE PATIENTS M A S 5% (95% CI: 3%-7%) N Engl J Med Recurrence Score vs Distant Recurrence in Node Negative, ER-Positive Breast Cancer Prognosis Laboratory Director: Patrick Joseph, MD Patient/ID: Sex: DOB: E L QUANTITATIVE SINGLE GENE REPORT type ER Score = Positive P Clinical Experience: M A S PR Score = Positive HER2 Score = Negative ASCO Breast Cancer Symposium 2007 ASCO Annual Meeting 2005 ASCO Breast Cancer Symposium 2008 This test was developed and its performance characteristics determined by Genomic Health, Inc. The laboratory is regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. These results are adjunctive to the ordering physician's workup. Laboratory Director: Patrick Joseph, MD This test was developed and its performance characteristics determined by Genomic Health, Inc. The laboratory is regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing. This test is used for clinical purposes. It should not be regarded as investigational or for research. These results are adjunctive to the ordering physician's workup. type type Also available for node-positive patients and patients with ductal carcinoma in situ 10 Requisition: Order Received: Date Reported:

Genomic Health is committed to making Oncotype DX available to your patients Sign up now for the Customer Portal at https://online.genomichealth.com for online ordering and results Call Customer Service at 866-ONCOTYPE to open an account Ensuring access to the Oncotype DX assay for invasive breast cancer Extensively reimbursed in node-negative disease: more than 95% of privately insured lives and Medicare beneficiaries are covered Expanding coverage in node-positive patients Provides comprehensive services to ease the reimbursement process for you, your staff, and your patients through the Genomic Access Program (GAP) GAP provides several assistance programs designed to help patients based on financial eligibility Genomic Health is a CLIA-certified, CAP-accredited reference laboratory Oncotype DX is now available for patients with ductal carcinoma in situ (DCIS) and stage II colon cancer References: 1. Hornberger J, Chien R. Meta-analysis of the decision impact of the 21-gene breast cancer Recurrence Score in clinical practice. Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX. Poster P2-09-06. 2. Asad J, Jacobson A, Estabrook A, et al. Does Oncotype DX recurrence score affect the management of patients with earlystage breast cancer? Am J Surg. 2008;196:527-529. 3. Henry L, Stojadinovic A, Swain S, et al. The influence of a gene expression profile on breast cancer decisions. J Surg Oncol. 2009;99:319-323. 4. Klang S, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health. 2010;13:381-387. 5. Liang H, Brufsky A, Lembersky B, Rastogi P, Vogel V. A retrospective analysis of the impact of Oncotype DX low recurrence score results on treatment decisions in a single academic breast cancer center. Presented at: 30th Annual San Antonio Breast Cancer Symposium; December 13-16, 2007; San Antonio, TX. Abstract 2062. 6. Lo S, Norton J, Mumby P, et al. Prospective multicenter study of the impact of the 21-gene Recurrence Score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol. 2010;28:1671-1676. 7. Oratz R, Paul D, Cohn A, Sedlacek S. Impact of a commercial reference laboratory test Recurrence Score on decision making in early-stage breast cancer. J Oncol Pract. 2007;3:182-186. 8. Thanasoulis T, Brown A, Frazier T. The role of Oncotype DX assay on appropriate treatment for estrogen positive, lymph node negative invasive breast cancer. Presented at: American Society of Breast Surgeons Annual Meeting; April 30-May 4, 2008; New York, NY. 9. Hornberger J, Cosler L, Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node negative, estrogen-receptor positive, early-stage breast cancer. Am J Manag Care. 2005;11:313-324. 10. Hornberger J, Chien R, Drebs K, Hochheiser L. US insurance program s experience with a multigene assay for early-stage breast cancer. J Oncol Pract. 2011;7:e38s-e45s. 11. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology : Breast cancer. Version 2.2011. Available at: www.nccn.org. Accessed September 29, 2011. 12. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;33:5287-5312. 13. Goldhirsch A, Wood W, Coates A, Gelber R, Thürlimann B, Senn H-J, and Panel members. Strategies for subtypes dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736-1747. 14. Simon R, Paik S, Hayes D. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst. 2009;101:1446-1452. 15. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor positive breast cancer. J Clin Oncol. 2006;24:3726-3734. 16. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817-2826. 17. Habel L, Shak S, Jacobs M, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res. 2006;8:R25-R39. 18. Dowsett M, Cuzick J, Wale C, et al. Prediction of risk of distant recurrence using the 21-gene Recurrence Score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC Study. J Clin Oncol. 2010;28:1829-1834. 19. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55-65. 20. St Gallen International Breast Cancer Expert Panel Guidelines include Oncotype DX as predictor of chemotherapy benefit [news release]. Geneva, Switzerland and Redwood City, CA: Genomic Health, Inc; July 25, 2011. Available at: http://files. shareholder.com/downloads/ghdx/1267502214x0x485384/1a583a8c-38a6-41b1-8166-9e07503598a7/ghdx_news_2011_7_25_general.pdf. Accessed October 3, 2011. 21. Paik S, Shak S, Tang G, et al. Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. J Clin Oncol. 2005;23(suppl 16S). Abstract 510. 22. Goldstein L, Gray R, Badve S, et al. Prognostic utility of the 21-gene assay in hormone receptor positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol. 2008;26:4063-4071. 23. Paik S, Shak S, Tang G, et al. Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients NSABP studies B-20 and B-14. Presented at: 26th Annual San Antonio Breast Cancer Symposium; December 3-6, 2003; San Antonio, TX. Abstract 16. 24. Esteban J, Baker J, Cronin M, et al. Tumor gene expression and prognosis in breast cancer: multi-gene RT-PCR assay of paraffin-embedded tissue. Presented at: 39th Annual Meeting of the American Society of Clinical Oncology; May 31-June 3, 2003; Chicago, IL. Abstract 3416. 25. Cobleigh M, Tabesh B, Bitterman P, et al. Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res. 2005;11:8623-8631. 26. Esteva F, Sahin A, Massimo C, et al. Prognostic role of a multigene reverse transcriptase-pcr assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res. 2005;11:3315-3319. 27. Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 2005;23:7265-7277. 28. Toi M, Iwata H, Yamanaka T, et al. Clinical significance of the 21-gene signature (Oncotype DX) in hormone receptor-positive early stage primary breast cancer in the Japanese population. Cancer. 2010;116:3112-3118. 29. Genomic Health presents ten new studies in breast, colon and prostate cancers at the American Society of Clinical Oncology (ASCO) Annual Meeting [press release]. Chicago, IL: Genomic Health, Inc; June 4, 2011. Available at: http://investor.genomichealth.com/releasedetail. cfm?releaseid=582751. Accessed October 3, 2011. 11

Oncotype DX reveals the underlying biology that changes treatment decisions 37% of the time Even when treatment decisions based on traditional measures seem conclusive, Oncotype DX can lead to a different approach Oncotype DX: Provides an individualized Recurrence Score result that cannot be predicted by traditional clinicopathologic variables 15 Is the only assay incorporated into NCCN, ASCO, and St Gallen clinical practice guidelines 11-13 Is the first commercial multigene expression assay to predict the benefit of chemotherapy in patients with ER-positive, HER2-negative breast cancer 20 Fulfills the criteria for National Cancer Institute Level I, Category B evidence, with consistent results in more than one prospective validation study using archived samples 14 Has been clinically validated in 13 studies with over 4,000 breast cancer patients 15-19,21-28 Can spare patients the negative health and quality of life impact of unnecessary chemotherapy and result in cost savings 1,6,9,10 Has the longest history and track record of commercial genomic assays with over 200,000 patients tested 29 For Customer Service, please contact within the United States 866-ONCOTYPE (866-662-6897) customerservice@genomichealth.com outside the United States +1-650-569-2028 international@genomichealth.com www.oncotypedx.com For newly diagnosed patients with node-negative or node-positive, ER-positive, HER2-negative invasive breast cancer NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network. ASCO is a trademark of the American Society of Clinical Oncology. NCCN and ASCO do not endorse any therapy or product. Genomic Health, Oncotype DX, Recurrence Score, and Uncover the Unexpected are trademarks of Genomic Health, Inc. 2012 Genomic Health, Inc. All rights reserved. GHI10005_0112 Uncover the Unexpected TM