She counts on your breast cancer expertise at the most vulnerable time of her life.

Transcription

1 HOME She counts on your breast cancer expertise at the most vulnerable time of her life. Empowering the right treatment choice for better patient outcomes. The comprehensive genomic assay experts trust. Incorporated in guidelines: NCCN 1 ASCO 2 ESMO 3 NICE ST. GALLEN CONSENSUS4 DIAGNOSTICS GUIDANCE5

2 FROM THE MOMENT SHE IS DIAGNOSED, YOUR PATIENT COUNTS ON YOU TO RECOMMEND THE BEST COURSE OF ACTION. HOME YOU CAN COUNT ON ONCOTYPE DX BREAST RECURRENCE SCORE. OVER A DECADE OF CONFIDENCE Oncotype DX Breast Recurrence Score provides a genomic-based, comprehensive, and individualized risk assessment that helps refine treatment decisions: Prospective outcomes in over 50,000 patients identifies patients who 6-9 : Can be spared chemotherapy and effectively treated with hormonal therapy alone Will benefit from the addition of chemotherapy Only the Recurrence Score result provides prognostic and predictive information to help establish who would benefit from chemotherapy DELIVERS CRITICAL GENOMIC INFORMATION NO OTHER ASSAY OR RISK ASSESSMENT METHOD PROVIDES, ENABLING YOU TO: Predict the benefit of adjuvant chemotherapy and endocrine therapy Now with prospective outcomes in over 50,000 patients 6-9 Identify patients with a low Recurrence Score result who can be spared aggressive treatment, as confirmed in outcomes studies 6-9 Refine the estimate of individual risk as a personalized Recurrence Score result on a continuum of ,13 Quantitatively assess the risk of distant recurrence in years 5 15 (late recurrence) 14 Base your treatment decisions on a clear picture of individual tumor biology Data on the association of the Recurrence Score result with risk of locoregional recurrence (LRR) and the risk of distant recurrence in years 5 15 (late recurrence) 14 are available upon request.

3 EMPOWERING THE RIGHT TREATMENT CHOICES FOR HOME BETTER PATIENT EARLY STAGE ER (+) HER2 ( ) NODE ( ) NODE (+) FOR EARLY-STAGE, ER-POSITIVE, HER2-NEGATIVE, NODE-NEGATIVE, AND (1 3) NODE-POSITIVE PATIENTS WITH INVASIVE BREAST CANCER By testing every eligible patient after surgery but before you discuss her treatment plan, you can determine who can be safely spared chemotherapy and effectively treated with hormonal therapy alone.

4 RECURRENCE SCORE RESULT PROVIDES AN INDIVIDUAL PICTURE OF THE PATIENT S UNIQUE TUMOR BIOLOGY IN NODE-NEGATIVE PATIENTS 10,12,13,15 HOME RATE OF DISTANT RECURRENCE AT 10 YEARS (%) LOW RISK GROUP AVERAGE: 6.8% 95% CI: 4.0% 9.6% INTERMEDIATE RISK GROUP AVERAGE: 14.3% 95% CI: 8.3% 20.3% HIGH RISK GROUP AVERAGE: 30.5% 95% CI: 23.6% 37.4% RATE 95% CI PATIENT AS COMPARED TO CLINICAL TRIAL RECURRENCE SCORE RESULT LOW RECURRENCE SCORE DISEASE= INDOLENT HORMONAL-THERAPY SENSITIVE LITTLE TO NO CHEMOTHERAPY BENEFIT HIGH RECURRENCE SCORE DISEASE= AGGRESSIVE LESS SENSITIVE TO HORMONAL THERAPY LARGE CHEMOTHERAPY BENEFIT

5 THE ONLY GENOMIC TEST THAT EMPOWERS THE RIGHT TREATMENT CHOICE FOR ALL ELIGIBLE PATIENTS HOME STANDARD OF CARE PROVEN VALIDATED CHANGED TREATMENT BENEFITED 600,000 + with prospective outcomes in over 50,000 patients 6-9 and incorporation into major clinical guidelines (NCCN, 1 ASCO, 2 and ESMO 3 ), St. Gallen Consensus, 4 and diagnostic guidance (NICE 5 ) in clinical evidence and utility studies with over 10,000 breast cancer patients in multiple studies with consistent results; the only multigene breast cancer assay with Level 1 evidence for risk of distant recurrence and prediction of chemotherapy benefit 10,11,13,15,19 decisions in more than 30% of patients in over 14 independent studies across 10 countries (range 24%-51%) 17,20-33 Oncotype DX tests for breast, colon, and prostate cancers have helped over half a million patients make more informed treatment choices 34

6 ONCOTYPE DX BREAST RECURRENCE SCORE : THE ONLY GENOMIC ASSAY WITH PROSPECTIVE IN OVER 50,000 PATIENTS 6-9 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL TAILORx Trial pn0 SEER Study pn0-pn1 Clalit Study pn0, pn1mi WSG PlanB Trial pn0-pn1 1,626 Patients > 44,500 Patients 2,028 Patients 2,642 Patients Recurrence Score result < 11 5-year distant recurrence-free survival rate of > 99% Recurrence Score result < 18 5-year breast cancer-specific survival rate of > 99% Recurrence Score result < 18 5-year distant recurrence-free survival and breast cancer-specific survival rates of > 99% Recurrence Score result 11 5-year disease-free survival rate of 94% > 50K Patients Power in numbers: Prospective outcomes in 50,000+ patients TAILORx Trial: First prospective outcomes providing Level 1A evidence show that patients with low Recurrence Score results (RS < 11) may be effectively and safely treated with hormonal therapy alone. 6 SEER Study: The largest molecularly characterized cohort of patients with prospective outcomes in Oncotype DX tested patients. Confirms the clinical utility of the Recurrence Score result with consistent results to those seen in the TAILORx Trial for patients with a low Recurrence Score result (RS < 18). 7 Clalit Study: Additional confirmation in a prospective registry in 2,000+ patients shows that the Recurrence Score result identifies patients who can safely be spared the addition of chemotherapy. 8 WSG PlanB Trial: Confirmation of the clinical utility of the Recurrence Score result in nodepositive and clinically high-risk node-negative patients with Level 1A evidence shows that patients with low Recurrence Score results (RS 11) can be safely spared chemotherapy. 9

7 HOME TAILORX TRIAL DATA CONFIRMS PATIENTS WITH LOW RECURRENCE SCORE RESULTS (RS < 11) MAY BE EFFECTIVELY AND SAFELY TREATED WITH HORMONAL THERAPY ALONE 6 TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL The Trial Assigning Individualized Options for Treatment (TAILORx): One of the largest prospective trials using a genomic assay to stratify breast cancer patients and determine treatment Results provide the highest level of evidence (Level 1A) Prospective 4-arm trial: Enrolled 10,253 node-negative, ER-positive, HER2-negative patients at 1,182 sites in 6 countries from April 2006 to October 2010 Stratified all treatment by the Recurrence Score result < 11 HORMONAL THERAPY ALONE ARM A N = 1,626* HORMONAL THERAPY ALONE ARM B HORMONAL THERAPY + CHEMOTHERAPY ARM C N = 6,885 (THIS GROUP WAS RANDOMIZED BETWEEN THESE 2 TREATMENTS) > 25 HORMONAL THERAPY + CHEMOTHERAPY ARM D N = 1,520 *Reported September To determine the effect of chemotherapy, if any, in the mid-range Recurrence Score result group. The results of Arms B, C, and D will be reported at a later date. This assay is the most rigorously tested option and provides proof of the principle that we can develop reproducible predictive tests to select patients who should not receive chemotherapy. C Hudis, The New England Journal of Medicine, 2015.

8 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL TAILORX TRIAL DATA CONFIRMS PATIENTS WITH LOW RECURRENCE SCORE RESULTS (RS < 11) MAY BE EFFECTIVELY AND SAFELY TREATED WITH HORMONAL THERAPY ALONE 6 TAILORx Trial Arm A (patients treated with hormonal therapy alone) 1,626 low-risk patients (Recurrence Score result < 11) Primary 5-year outcomes 93.8% invasive disease-free survival Secondary 5-year outcomes 99.3% free of distant recurrence 98.7% free of recurrence, distant or local 98.0% rate of overall survival Neither age, size, nor grade impacted the 5-year distant recurrence risk or overall survival Distant recurrence AGE 50 VS YEARS 50 VS YEARS DRFI, HR (95% CI) 1.28 ( ) 3.49 ( ) P VALUE TUMOR SIZE > 2 CM VS 2 CM 1.55 ( ).55 TUMOR GRADE 2/3 VS ( ).14 DRFI = distant recurrence-free interval; HR = hazard ratio; CI = confidence interval Patient characteristics in Arm A: Age: 30% 50 years Tumor size: 31% > 2 cm; median 1.5 cm Tumor grade: 66% 2/3 At 5 years post-diagnosis: < 1% of patients experienced a distant recurrence event (10 events) < 1% of patients experienced a locoregional recurrence event (8 events) Conclusion: Women were 3x more likely to have new invasive cancer than to have a recurrence (58 new cancers, 15 of which were contralateral) 5-year distant recurrence risks in the TAILORx Trial were consistent with those seen in the original clinical validation study, NSABP B-14, at 5 years

9 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL TAILORX TRIAL DATA CONFIRMS PATIENTS WITH LOW RECURRENCE SCORE RESULTS (RS < 11) MAY BE EFFECTIVELY AND SAFELY TREATED WITH HORMONAL THERAPY ALONE 6 TAILORx Trial Arm A (patients treated with hormonal therapy alone) Event rates by tumor grade DRFI, % (95% CI) OS, % (95% CI) ALL GRADES 99.3 ( ) 98.0 ( ) LOW GRADE 99.8 ( ) 98.7 ( ) INTERMEDIATE GRADE 99.0 ( ) 97.9 ( ) HIGH GRADE 100 (NC-NC) 97.3 ( ) CI = confidence interval; DRFI = distant recurrence free interval; HR = hazard ratio; NC = not calculated; OS = overall survival No distant recurrence events among patients with high-grade tumors Only 0.7% of patients across all grades experienced a distant recurrence event

10 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL SEER STUDY: REAL-WORLD CLINICAL UTILITY IN 38,000+ NODE-NEGATIVE PATIENTS SHOWS THAT THE RECURRENCE SCORE RESULT ACCURATELY IDENTIFIES PATIENTS WHO DO WELL WITH HORMONAL THERAPY ALONE 7 5-year breast cancer specific mortality (BCSM) by Recurrence Score group Primary analysis: Node-negative, HR-positive, HER2-negative patients years old (N = 38,568) 5-YEAR BREAST CANCER-SPECIFIC MORTALITY (%) The BCSM in patients with: RS GROUP N EVENTS 5-YR BCSM (95% CI) RS (< 18) (0.3% to 0.6%) RS (18 30) (1.1% to 1.7%) RS ( 31) (3.4% to 5.6%) LOG RANK P < MONTHS FROM PRIMARY CANCER DIAGNOSIS RS < 18 was 0.4% (45 events), where 7% of patients were treated with chemotherapy RS was 1.4% (107 events), where 34% of patients were treated with chemotherapy RS 31 was 4.4% (71 events), where 69% of patients were treated with chemotherapy The results in the low Recurrence Score group are consistent with the results in the TAILORx Trial among patients with Recurrence Score results < 11. For patients with a low Recurrence Score result, it is unlikely that adding chemotherapy would provide additional clinical benefit. ENLARGE

11 SEER STUDY: NODE-POSITIVE PATIENTS WITH LOW RECURRENCE SCORE RESULTS DO WELL WITH HORMONAL THERAPY ALONE 7 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL For node-positive patients with low Recurrence Score results, it is unlikely that adding chemotherapy will provide clinical benefit Prospective breast cancer-specific mortality (BCSM) outcomes in SEER for node-positive (mic, 1-3) disease 5-YEAR BREAST CANCER-SPECIFIC MORTALITY (%) % LOW N = 2, % INTERMEDIATE N = 1, % HIGH N = 328 Largest cohort of node-positive patients with a genomic assay with Recurrence Score result guided treatment and outcomes. In node-positive patients, chemotherapy is standard of care, yet patients with: RS < 18 (2,694 patients) had 5-year BCSM of 1.0% RS (1,669 patients) had 5-year BCSM of 2.3% Known chemotherapy use: Low 23.0% Intermediate 46.5% High 75.3% Results supported by NCCN guidelines for patients with 1-3 positive nodes: consider the 21-gene assay to guide the addition of chemotherapy to standard hormonal therapy. 1

12 HOME CLALIT REGISTRY*: REAL-WORLD COHORT WITH 2,000+ PATIENTS PROVIDES FURTHER EVIDENCE THAT THE RECURRENCE SCORE RESULT IDENTIFIES PATIENTS WHO MAY BE SPARED CHEMOTHERAPY 8 TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL 2,028 patients with 6.1-year median follow-up Recurrence Score result guided treatment decisions 5-YEAR DISTANT RECURRENCE RISK (%) YEAR DISTANT RECURRENCE (DR) RATE RECURRENCE SCORE RISK GROUP N 5-YR RISK (95% CI) High ( 31) % (7.2% to 15.5%) Int (18 30) % (2.2% to 4.7%) Low (< 18) % (0.4% to 1.6%) LOG RANK P < YEARS ENLARGE RISK OF BC DEATH (%) YEAR BREAST CANCER-SPECIFIC MORTALITY (BCSM) RECURRENCE SCORE RISK GROUP N 5-YR RISK (95% CI) High ( 31) % (4.1% to 11.25%) Int (18 30) % (0.5% to 2.1%) Low (< 18) % (0.0% to 0.0%) LOG RANK P < YEARS Patients with low (RS < 18) and intermediate (RS 18-30) Recurrence Score results in this study did extremely well with appropriate hormonal treatment It is unlikely that chemotherapy would provide any incremental benefit ENLARGE These results from a real-world cohort of node-negative and pn1mi patients are consistent with previously reported results in the TAILORx Trial and the SEER Study. * Clalit Registry is the largest health provider in Israel and mandates physicians use the Recurrence Score result for treatment decisions.

13 HOME TAILORx TRIAL SEER STUDY CLALIT STUDY WSG PlanB TRIAL WSG* PlanB: PROSPECTIVE RANDOMIZED TRIAL SHOWS THAT PATIENTS WITH HIGH CLINICAL RISK DISEASE WITH LOW RECURRENCE SCORE RESULTS MAY BE SAFELY SPARED CHEMOTHERAPY 9 West German Study Group Phase 3 PlanB Trial Early-stage HER2 breast cancer; node-positive or high-risk node-negative HR T 75 C 600 x 6 HR+ pn0 = 1,554 pn1 = 1,088 N = 2,642 RS N0-3 and RS > 11 N0-3 and RS 11 N = 348 *West German Study Group. Node-positive (N+) patients had T1-4, grade 1-3, and HR+ or HR- disease. High-risk node-negative (N0) had T > 2 cm, grade 2-3, or HR- disease, had elevated upa/pai-1 levels, or were 35 years of age. Endocrine therapy and radiation therapy according to national guidelines. Distribution of Recurrence Score results 21% > 25 18% 11 60% year Disease-Free Survival Distribution of Recurrence Score results is similar to other studies such as the TAILORx Trial Only 21% of clinically highrisk patients had RS > 25 RS 11 94% No chemotherapy RS % + chemotherapy RS > 25 84% + chemotherapy R E 90 C 600 x 4 Doc 100 x 4 Endocrine therapy Study conclusions 5-year disease-free survival in node-positive and high-risk node-negative patients with RS 11 (94%) is similar to the TAILORx Trial result in node-negative patients with RS < 11 (93.8%), further confirming that patients with a low Recurrence Score result can be safely spared chemotherapy These low Recurrence Score result patients also have the same 5-year disease-free survival as patients with Recurrence Score results (94%), who were all treated with chemotherapy, which suggests that there was little benefit of chemotherapy in the Recurrence Score group

14 RECURRENCE SCORE RESULT PROVIDES AN IMPROVED ESTIMATE OF RISK OF RECURRENCE HOME NSABP B-14 Study 10-year rate of distant recurrence was significantly lower for patients with low Recurrence Score results compared to high results 13 PROGNOSTIC, NODE PREDICTIVE, NODE PROGNOSTIC, NODE + PREDICTIVE, NODE + RATE OF DISTANT RECURRENCE AT 10 YEARS (%) LOW RISK RECURRENCE SCORE RESULT <18 6.8% 95% CI: 4.0%-9.6% INTERMEDIATE RISK RECURRENCE SCORE RESULT % 95% CI: 8.3%-20.3% HIGH RISK RECURRENCE SCORE RESULT % 95% CI: 23.6%-37.4% LOW RECURRENCE SCORE RESULT= LOWER RATE OF DISTANT RECURRENCE 13 HIGH RECURRENCE SCORE RESULT= HIGHER RATE OF DISTANT RECURRENCE 13 PROGNOSTIC: Having the ability to predict the clinical outcome.

15 RECURRENCE SCORE RESULT PREDICTS THE MAGNITUDE OF CHEMOTHERAPY BENEFIT FOR NODE-NEGATIVE PATIENTS HOME PROGNOSTIC, NODE PREDICTIVE, NODE PROGNOSTIC, NODE + NSABP B-20 Study Low Recurrence Score result predicted little to no benefit from chemotherapy 10 LOW RECURRENCE SCORE RESULT (<18) LITTLE TO NO CHEMOTHERAPY BENEFIT 97% PROPORTION WITHOUT DISTANT RECURRENCE ENLARGE P =.61 N EVENTS TAM + CHEMO TAM % YEARS INTERMEDIATE RECURRENCE SCORE RESULT (18 30) NO SUBSTANTIAL CHEMOTHERAPY BENEFIT PROPORTION WITHOUT DISTANT RECURRENCE ENLARGE P =.39 N EVENTS TAM + CHEMO 89 9 TAM % 89% YEARS PREDICTIVE, NODE + NSABP B-20 Study High Recurrence Score result predicted large benefit from chemotherapy 10 HIGH RECURRENCE SCORE RESULT ( 31) LARGE CHEMOTHERAPY BENEFIT PROPORTION WITHOUT DISTANT RECURRENCE ENLARGE P <. 001 N EVENTS TAM + CHEMO TAM % 60% YEARS 28% ABSOLUTE BENEFIT FROM TAM + CHEMOTHERAPY Recurrence Score result is associated with the magnitude of chemotherapy benefit for node-negative patients. 10 PREDICTIVE: Having the ability to predict the response to a specific treatment (benefit).

16 RECURRENCE SCORE RESULT PROVIDES AN IMPROVED ESTIMATE OF RISK OF RECURRENCE HOME PROGNOSTIC, NODE PREDICTIVE, NODE PROGNOSTIC, NODE + PREDICTIVE, NODE + 9-YEAR RISK OF DISTANT RECURRENCE (%) TransATAC Study Rate of distant recurrence increases with the number of positive nodes for all Recurrence Score values RECURRENCE SCORE RESULT LOW RECURRENCE SCORE RESULT = LOW RECURRENCE SCORE RESULT= LOWER RATE OF DISTANT RECURRENCE POSITIVE NODES N=63 (31 EVENTS) 1 3 POSITIVE NODES N=243 (43 EVENTS) NODE NEGATIVE N=872 (72 EVENTS) Recurrence Score result provides important prognostic information about the estimated risk of distant recurrence for node-positive patients. 19 MEAN 95% CI PROGNOSTIC: Having the ability to predict the clinical outcome. THE 9-YEAR RISK OF DISTANT RECURRENCE INCREASED WITH THE NUMBER OF POSITIVE NODES AND THE RECURRENCE SCORE RESULT THE 9-YEAR RISK OF DISTANT RECURRENCE FOR NODE-NEGATIVE PATIENTS AND THOSE WITH 1 3 POSITIVE NODES WAS SIMILAR HIGH RECURRENCE SCORE RESULT= HIGHER RATE OF DISTANT RECURRENCE 19

17 RECURRENCE SCORE RESULT PREDICTS THE MAGNITUDE OF CHEMOTHERAPY BENEFIT FOR NODE-POSITIVE PATIENTS HOME SWOG 8814 Study LOW RECURRENCE SCORE RESULT (< 18) LITTLE TO NO CHEMOTHERAPY BENEFIT INTERMEDIATE RECURRENCE SCORE RESULT (18 30) NO SUBSTANTIAL CHEMOTHERAPY BENEFIT PROGNOSTIC, NODE PREDICTIVE, NODE PROGNOSTIC, NODE + Low Recurrence Score result predicted little to no benefit from chemotherapy 11 BREAST CANCER-SPECIFIC SURVIVAL P =.56 N EVENTS TAM ONLY 55 4 CAF-T % 87% YEARS ENLARGE BREAST CANCER-SPECIFIC SURVIVAL P =.89 N EVENTS TAM ONLY CAF-T % 70% YEARS ENLARGE PREDICTIVE, NODE + SWOG 8814 Study High Recurrence Score result predicted large benefit from chemotherapy 11 HIGH RECURRENCE SCORE RESULT ( 31) LARGE CHEMOTHERAPY BENEFIT BREAST CANCER-SPECIFIC SURVIVAL P =.033 N EVENTS TAM ONLY CAF-T % 54% YEARS 19% ABSOLUTE BENEFIT FROM CHEMOTHERAPY ENLARGE Recurrence Score result is associated with the magnitude of chemotherapy benefit for node-positive patients. 11 PREDICTIVE: Having the ability to predict the response to a specific treatment (benefit).

18 ONCOTYPE DX BREAST RECURRENCE SCORE PROVIDES INFORMATION HOME TUMOR SIZE PATIENT AGE TUMOR GRADE TUMOR SIZE PATIENT AGE TUMOR GRADE Traditional clinical and pathologic factors cannot predict the Recurrence Score result The Recurrence Score result reflects the individual biology of ER-positive patients; traditional factors (tumor size and grade, patient age) do not. This insight enables physicians to assess risk based on a patient s specific underlying disease. 10 The Recurrence Score result provides important prognostic information about the estimated risk of distant recurrence for node-negative patients 13 While tumor size, patient age, and tumor grade are modest prognosticators of distant recurrence, the Recurrence Score result provides strong and consistent information beyond traditional clinical and pathologic features in all patient subgroups. 13 PROGNOSTIC: Having the ability to predict the clinical outcome.

19 ONCOTYPE DX BREAST RECURRENCE SCORE PROVIDES INFORMATION HOME TUMOR SIZE PATIENT AGE TUMOR GRADE Tumor size does not reveal the whole picture of the tumor biology 10 Risk of distant recurrence across tumor size 13 TUMOR SIZE PATIENT AGE TUMOR GRADE RECURRENCE SCORE RESULT PATIENTS WITH SMALL TUMORS CAN HAVE HIGH RECURRENCE SCORE RESULTS 16% 20% 64% 1 (N=110) 25% 19% 56% 30% 23% 46% CLINICAL TUMOR SIZE SIZE (CM) (CM) PATIENTS WITH LARGE TUMORS CAN HAVE LOW RECURRENCE SCORE RESULTS 33% 21% 46% (N=318) (N=196) >4 (N=24) TUMOR SIZE (CM) All N= % DISTANT RECURRENCE FREE AT 10 YEARS ENLARGE RECURRENCE SCORE RESULT < ENLARGE ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31)

20 ONCOTYPE DX BREAST RECURRENCE SCORE PROVIDES INFORMATION HOME TUMOR SIZE PATIENT AGE TUMOR GRADE Patient age does not reveal the whole picture of the tumor biology 10 Risk of distant recurrence across patient age 13 TUMOR SIZE PATIENT AGE TUMOR GRADE RECURRENCE SCORE RESULT YOUNGER PATIENTS CAN HAVE LOW RECURRENCE SCORE RESULTS 41% 24% 28% 19% 14% 21% 22% 21 % 44% 55% 50% PATIENT ENT AGE AGE (YEARS) OLDER PATIENTS CAN HAVE HIGH RECURRENCE SCORE RESULTS 60% < 40 (N=63) (N=226) (N=166) 60 (N=196) PATIENT AGE All N=668 < > % DISTANT RECURRENCE FREE AT 10 YEARS ENLARGE RECURRENCE SCORE RESULT < ENLARGE ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31)

21 ONCOTYPE DX BREAST RECURRENCE SCORE PROVIDES INFORMATION HOME TUMOR SIZE PATIENT AGE TUMOR GRADE Tumor grade does not reveal the whole picture of the tumor biology 10 Risk of distant recurrence across tumor grade 13 TUMOR SIZE PATIENT AGE TUMOR GRADE GRADING BY PATHOLOGIST AT LOCAL HOSPITAL RECURRENCE SCORE RESULT RECURRENCE SCORE RESULT % 12% 16% 73% 16% 73% 22% 22% 56% 22% 56% WELL (N=77) MODERATE (N=339) POOR (N=163) TUMOR GRADE (SITE) TUMOR GRADE (SITE) 42% 42% 22% 22% 36% 36% WELL (N=77) MODERATE (N=339) POOR (N=163) PATIENTS WITH LOW-GRADE TUMORS CAN HAVE HIGH RECURRENCE SCORE RESULTS TUMOR GRADE (SITE) Recurrence Score result < PATIENTS WITH HIGH-GRADE TUMORS CAN HAVE LOW RECURRENCE SCORE RESULTS TUMOR GRADE ALL WELL MODERATE POOR N= GRADING BY PATHOLOGIST AT CENTRAL LAB RECURRENCE SCORE RESULT % 12% 83% 12% 24% 64% 61% 19% 19% WELL (N=119) MODERATE (N=340) POOR (N=190) TUMOR GRADE (CENTRAL) TUMOR GRADE (CENTRAL) ENLARGE % DISTANT % RECURRENCE FREE AT AT YEARS YEARS ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31) ENLARGE RECURRENCE SCORE RESULT <

22 IDENTIFIED THROUGH A RIGOROUS AND RATIONAL SELECTION PROCESS DESCRIBED BY THE NATIONAL CANCER INSTITUTE HOME Identified optimal gene panel through candidate gene approach 250 cancer-related genes were chosen based on scientific data Candidate genes were tested in 3 independent studies with 447 breast cancer patients cancer genes Linked to critical molecular pathways in cancer Selected genes strongly associated with risk of breast cancer recurrence (prognosis) Selected genes strongly associated with chemotherapy benefit (prediction) Accuracy for HER2 is improved by looking at the GRB7/HER2 group 5 reference genes Normalize gene expression Provide quality control regarding inter-sample variability PROLIFERATION KI-67 STK15 SURVIVIN CYCLIN B1 MYBL2 ESTROGEN ER2 PR BCL-2 SCUBE2 INVASION STROMELYSIN 3 CATHEPSIN L2 OTHER GSTM1 CD68 BAG1 HER2 GRB7 HER2 REFERENCE BETA-ACTIN GAPDH RPLPO GUS TFRC 21-GENE PANEL Recurrence Score result = x HER2 group score 0.34 x Estrogen group score x Proliferation group score x Invasion group score x CD x GSTM x BAG1 13 RT-PCR has a wide 65,000-fold dynamic range of expression for the 16 cancer-related genes, 38 which allows for quantitative measurements. Oncotype DX Breast Recurrence Score was optimized to minimize variability and ensure reproducibility.

23 THE COMPREHENSIVE ONCOTYPE DX BREAST RECURRENCE SCORE REPORT LEADS TO MORE INFORMED PATIENT DISCUSSIONS HOME NODE-NEGATIVE REPORT NODE-POSITIVE [1-3+] REPORT NODE-POSITIVE [ 4+] REPORT Your patient may be making the most important decision of her life and she is counting on your guidance. Only Oncotype DX Breast Recurrence Score provides information about her unique tumor biology to help guide her individual decision. The clear, easy-to-read format of the breast cancer report helps you share that information a critical tool that enhances the conversation as you determine her treatment plan together QUANTITATIVE RISK OF RECURRENCE, INDIVIDUALIZED TO YOUR PATIENT THE MAGNITUDE OF CHEMOTHERAPY BENEFIT INCREASES AS THE RECURRENCE SCORE RESULT INCREASES THE MAGNITUDE OF HORMONAL THERAPY BENEFIT CORRELATES TO THE ER SCORE

24 COMPREHENSIVE SUPPORT HELPS KEEP YOU FOCUSED ON YOUR PATIENTS HOME ONCOTYPE DX BREAST RECURRENCE SCORE IS: Covered by Medicare and by most private insurance companies GAP Our internal experts available through the Genomic Access Program (GAP) can help ease the reimbursement process for you and your patients INFO FOR MORE INFORMATION ONCOTYPEDX.COM +1 (866) ONCOTYPE ( )

25 HOME ONCOTYPE DX BREAST RECURRENCE SCORE : PREDICTIVE AND PROGNOSTIC RESULTS YOU CAN COUNT ON FOR EVERY ELIGIBLE ER(+), HER2(-) PATIENT. STANDARD OF CARE with prospective outcomes in over 50,000 patients 6-9 and incorporation into major clinical practice guidelines 1-5 PROVEN to be both predictive of chemotherapy benefit and prognostic 10,11,13,19 VALIDATED BENEFITED 600,000+ in multiple studies with consistent results (Level 1 evidence for risk of distant recurrence and prediction of chemotherapy benefit) 10,11,13,15,19 Oncotype DX tests for breast, colon, and prostate cancers have helped over half a million patients make more informed treatment choices 34

26 HOME 1. NCCN Clinical Practice Guidelines in Oncology. V Harris et al. J Clin Oncol Senkus et al. Ann Oncol Coates et al. Ann Oncol NICE diagnostics guidance Sparano et al. N Engl J Med Shak et al. SABCS Stemmer et al. SABCS Gluz et al. EBCC Paik et al. J Clin Oncol Albain et al. Lancet Oncol Kim et al. J Clin Oncol Paik et al. N Engl J Med Wolmark et al. ASCO Habel et al. Breast Cancer Res Bayt et al. EBCC Levine et al. ASCO Vacirca et al. ASCO Dowsett et al. J Clin Oncol Geffen et al. Ann Oncol Albanell et al. Ann Oncol Davidson et al. Eur J Cancer Gligorov et al. ASCO Eiermann et al. Ann Oncol de Boer et al. Med J Aust Holt et al. Br J Cancer Yamauchi et al. ESMO Bargallo et al. ESMO Oratz et al. J Oncol Pract Liang et al. SABCS Klang et al. Value Health Lo et al. J Clin Oncol Oratz et al. J Oncol Pract Data on file, Genomic Health, Inc. 35. Paik et al. SABCS Cobleigh et al. Clin Cancer Res Esteban et al. ASCO Cronin et al. Am J Pathol Genomic Health, Oncotype DX, Oncotype IQ, Oncotype DX Breast Recurrence Score, and Recurrence Score are trademarks or registered trademarks of Genomic Health, Inc. NCCN is a registered trademark of the National Comprehensive Cancer Network. ASCO is a registered trademark of the American Society of Clinical Oncology. NCCN, ASCO, ESMO, St. Gallen, and NICE do not endorse any product or therapy Genomic Health, Inc. All rights reserved. GHI10678_0416

27 SEER Study 5-YEAR BREAST CANCER SPECIFIC MORTALITY (BCSM) BY RECURRENCE SCORE GROUP PRIMARY ANALYSIS: NODE-NEGATIVE, HR-POSITIVE, HER2-NEGATIVE PATIENTS YEARS OLD (N = 38,568) 5-YEAR BREAST CANCER-SPECIFIC MORTALITY (%) RS GROUP N EVENTS 5-YR BCSM (95% CI) RS (< 18) (0.3% to 0.6%) RS (18 30) (1.1% to 1.7%) RS ( 31) (3.4% to 5.6%) LOG RANK P < MONTHS FROM PRIMARY CANCER DIAGNOSIS RETURN

28 Clalit Study 5-YEAR DISTANT RECURRENCE (DR) RATE 5-YEAR DISTANT RECURRENCE RISK (%) RECURRENCE SCORE RISK GROUP LOG RANK P <.001 N 5-YR RISK (95% CI) High ( 31) % (7.2% to 15.5%) Int (18 30) % (2.2% to 4.7%) Low (< 18) % (0.4% to 1.6%) YEARS RETURN

29 Clalit Study 5-YEAR BREAST CANCER-SPECIFIC MORTALITY (BCSM) 50 RISK OF BC DEATH (%) RECURRENCE SCORE RISK GROUP LOG RANK P <.001 N 5-YR RISK (95% CI) High ( 31) % (4.1% to 11.25%) Int (18 30) % (0.5% to 2.1%) Low (< 18) % (0.0% to 0.0%) YEARS RETURN

30 NSABP B-20 Study LOW RECURRENCE SCORE RESULT (< 18) LITTLE TO NO CHEMOTHERAPY BENEFIT 97% PROPORTION WITHOUT DISTANT RECURRENCE P =.61 N Events TAM + CHEMO TAM % YEARS RETURN

31 NSABP B-20 Study INTERMEDIATE RECURRENCE SCORE RESULT (18 30) NO SUBSTANTIAL CHEMOTHERAPY BENEFIT PROPORTION WITHOUT DISTANT RECURRENCE P =.39 N Events TAM + CHEMO 89 9 TAM % 89% YEARS RETURN

32 NSABP B-20 Study HIGH RECURRENCE SCORE RESULT ( 31) LARGE CHEMOTHERAPY BENEFIT PROPORTION WITHOUT DISTANT RECURRENCE P <.001 N Events TAM + CHEMO TAM % 60% 28% ABSOLUTE BENEFIT FROM TAM + CHEMOTHERAPY YEARS RETURN

33 SWOG 8814 Study LOW RECURRENCE SCORE RESULT (< 18) LITTLE TO NO CHEMOTHERAPY BENEFIT % BREAST CANCER SPECIFIC SURVIVAL P =.56 N Events TAM ONLY % CAF-T YEARS RETURN

34 SWOG 8814 Study INTERMEDIATE RECURRENCE SCORE RESULT (18 30) NO SUBSTANTIAL CHEMOTHERAPY BENEFIT 1.00 BREAST CANCER SPECIFIC SURVIVAL P =.89 N Events TAM ONLY % 70% CAF-T YEARS RETURN

35 SWOG 8814 Study HIGH RECURRENCE SCORE RESULT ( 31) LARGE CHEMOTHERAPY BENEFIT 1.00 BREAST CANCER SPECIFIC SURVIVAL P =.033 N Events TAM ONLY % 54% 19% ABSOLUTE BENEFIT FROM CHEMOTHERAPY CAF-T YEARS RETURN

36 Tumor size does not reveal the whole picture of the tumor biology 10 PATIENTS WITH SMALL TUMORS CAN HAVE HIGH RECURRENCE SCORE RESULTS PATIENTS WITH LARGE TUMORS CAN HAVE LOW RECURRENCE SCORE RESULTS RECURRENCE SCORE RESULT % 20% 64% 25% 19% 56% 30% 23% 46% 33% 21% 46% 1 (N=110) (N=318) (N=196) >4 (N=24) CLINICAL TUMOR SIZE (CM) RECURRENCE SCORE RESULT < RETURN

37 Risk of distant recurrence across tumor size 13 All N=668 TUMOR SIZE (CM) % DISTANT RECURRENCE FREE AT 10 YEARS ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31) RETURN

38 Patient age does not reveal the whole picture of the tumor biology 10 YOUNGER PATIENTS CAN HAVE LOW RECURRENCE SCORE RESULTS OLDER PATIENTS CAN HAVE HIGH RECURRENCE SCORE RESULTS RECURRENCE SCORE RESULT % 24% 28% 19% 14% 44% 21% 55% 22% 50% 21 % 60% < 40 (N=63) (N=226) (N=166) 60 (N=196) PATI ENT AGE (YEARS) RECURRENCE SCORE RESULT < RETURN

39 Risk of distant recurrence across patient age 13 All N=668 PATIENT AGE < > % DISTANT RECURRENCE FREE AT 10 YEARS ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31) RETURN

40 RECURRENCE SCORE SCORE RESULT RESULT % 12% 16% 73% 16% 73% 22% 22% 56% 22% 56% WELL (N=77) MODERATE (N=339) POOR (N=163) TUMOR GRADE (SITE) TUMOR GRADE (SITE) 42% 42% 22% 22% 36% 36% WELL (N=77) MODERATE (N=339) POOR (N=163) Recurrence Score result < Tumor grade does not reveal the whole picture of the tumor biology 10 GRADING BY PATHOLOGIST AT LOCAL HOSPITAL PATIENTS WITH LOW-GRADE TUMORS CAN HAVE HIGH RECURRENCE SCORE RESULTS PATIENTS WITH HIGH-GRADE TUMORS CAN HAVE LOW RECURRENCE SCORE RESULTS RECURRENCE SCORE RESULT % 12% 83% RECURRENCE SCORE RESULT < % 24% 64% WELL (N=119) MODERATE (N=340) POOR (N=190) TUMOR GRADE (CENTRAL) 61% 19% 19% GRADING BY PATHOLOGIST AT CENTRAL LAB RETURN

41 Risk of distant recurrence across tumor grade 13 ALL N=668 TUMOR GRADE WELL MODERATE POOR % DISTANT RECURRENCE FREE AT 10 YEARS ALL PATIENTS LOW RISK (RECURRENCE SCORE RESULT < 18) INTERMEDIATE RISK (RECURRENCE SCORE RESULT 18 30) HIGH RISK (RECURRENCE SCORE RESULT 31) RETURN

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