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Oncotype DX a Genomic Approach to Breast Cancer

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Presentation on theme: "Oncotype DX a Genomic Approach to Breast Cancer"— Presentation transcript:

1 Oncotype DX a Genomic Approach to Breast Cancer
GHI10006_1211

2 Pathology: 20th and 21st Century
As morphologists, pathologists are expert at examining fixed paraffin sections which have been stained with hematoxylin and eosin. By identifying mitotic figures the pathologist is able to assess the proliferative activity of a cell. Immunohistochemical stains for the Ki-67 protein allow for direct monitoring of the growth fraction of normal and neoplastic cells. Size Age Phenotype Nodal status Protein/Gene “Genomic Profiling”

3 Role of Traditional Markers in ER+ EBC
Markers are used to determine diagnosis, estimate prognosis and to inform treatment decisions Some markers (tumour grade, nodal status and genomic tests) are prognostic; some are predictive of treatment benefit. Some are both predictive and prognostic (ER, PR, HER2 and Oncotype DX® assay) Standardisation and / or reproducibility of a test may present a challenge Variability in interpretation of results Despite the use of many markers, a large proportion of patients are classified as intermediate risk and there is a population in whom treatment decisions are not clear Cianfrocca and Goldstein. Oncologist. 2004;9(6): ; Lonning PE. Ann Oncol. 2007;18(suppl 8):viii3-viii7

4 What are Genetics and Genomics?
Genes (units of heredity) carry the instructions for making proteins, which direct the activities of cells and functions of the body Study of a single gene, its roles in inheritance and its effects Examples of genetic disorders include cystic fibrosis, Huntington's disease, and in oncology; BRCA Genomics Study of all of a person's genes (the genome), interactions of the genes with each other and with the environment Study of complex diseases such as heart disease, asthma, diabetes, and cancer because these diseases are typically caused more by a combination of genetic and environmental factors than by individual genes

5 Oncotype DX® Breast Test
It is a genomic test of the expression of 21 genes (16 tumor genes and 5 housekeeping genes) Utilizes RT-PCR technology on FFPE tissue Quantitatively predicts the likelihood of breast cancer recurrence in women with newly diagnosed, early stage invasive breast cancer Assesses the likely benefit from both hormonal therapy and chemotherapy Is the only multi-parameter gene expression assay to show clinical utility in breast cancer Is recommended by clinical practice guidelines (St Gallen, ESMO, ASCO, NCCN) and NICE The Oncotype DX assay quantitatively predicts the likelihood of recurrence in women with newly diagnosed, early stage invasive breast cancer. Oncotype DX assesses the likely benefit from both hormonal therapy and chemotherapy It is the only multi-parameter gene expression assay to show clinical utility in breast cancer, meaning that it has been shown to alter treatment decisions in a significant number of cases. It is the only multivariate genomic classifier recommended in both ASCO and NCCN clinical practice guidelines. Harris L, et al. J Clin Oncol. 2007;33(25): NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version Available at: Accessed December 8, 2008. 5

6 Oncotype DX® Breast Test Genes
16 CANCER RELATED GENES Estrogen Proliferation HER2 Invasion Others ER PR Bcl2 SCUBE2 Ki-67 STK15 Survivin Cyclin B1 MYBL2 GRB7 HER2 Stromelysin 3 Cathepsin L2 CD68 GSTM1 BAG1 The final gene set used for the Oncotype DX™ assay includes the 16 cancer genes identified in the clinical trials: 5 genes are in the proliferation group, 2 in the HER2 group, 4 in the estrogen receptor group, 2 in the invasion group, and 3 are unaligned. Some of the genes are well known in the breast cancer literature; others are relatively new. The 5 reference genes are used for normalizing the expression of the cancer-related genes. As was previously stated, it is important to note that there are other genes linked to breast cancer (e.g., the 250 candidate genes from which the 16 genes were selected). The 16 genes presented in this slide were selected for the Oncotype DX assay based on the three clinical trials, which demonstrated a consistent statistical link between these genes and distant breast cancer recurrence and the most robust predictive power across the three studies. Additional information on some of the 16 cancer related genes: MYBL2: The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses both activator and repressor activities. It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. Transcript variants may exist for this gene, but their full-length natures have not been determined. STK15: The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. Scube2 can modulate the long-range action of Bmp-dependent Hedgehog signaling in the neural tube and somites. STMY3 (MMP11): Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix CL2: The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that may play an important role in corneal physiology. This gene is expressed in colorectal and breast carcinomas but not in normal colon, mammary gland, or peritumoral tissues, suggesting a possible role for this gene in tumor processes. GSTM1: Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. BAG1: The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. At least three protein isoforms are encoded by this mRNA through the use of alternative translation initiation sites, including a non-AUG sit 5 Reference Genes Beta-actin GAPDH RPLPO GUS TFRC Paik et al. N Engl J Med. 2004;351: 6

7 The GHI lab has processed >400,000 tests from >70 countries
The centralisation of the Oncotype DX testing allows >97% reliability The GHI lab has processed >400,000 tests from >70 countries ORDER ENTRY INTAKE PATHOLOGY ANALYTICAL LABORATORY REPORT FULFILLMENT MATERIAL RETURN Order Entry Benefits Investigation Patient Information Retrieval Specimen Retrieval Accessioning Pathology Review Histopath Extraction Quantitation gDNA Detection Reverse Transcription Results Generation Billing Report Delivery Materials Return Online QPCR Online or Fax Phone Fax Request FedEX FedEx Success rate published: 98% for ODX / 80% for MP Test run in triplicate /samples reviewed by pathologist gene expression describes the transcription of information encoded within DNA sequences into messenger RNA (mRNA) – RTPCR quantitatively measure RNA expression levels of genes / cancer gene expression is normalised against expression level of reference gene 10-14 working days *Anderson JM et al, 2009.

8 Automation is Central to Laboratory Processes
8

9 The Oncotype DX® Breast Test Results
Quantifies expression of a panel of genes which is expressed as a Recurrence Score® The Recurrencence Score® is a continuous value ranging from 0 to 100; and classifies patients into 3 risk categories: Low (<18) – minimal benefit from adjuvant chemotherapy1,2 Intermediate (18-30) - ?1,2 High (≥31) - significant benefit from adjuvant chemotherapy1,2 Paik et al. J Clin Oncol. 2006;, Albain et al. Lancet Oncol 2010

10 The Precision of the Oncotype DX® Recurrence Score® Defines Individual Biology for ER Positive Breast Cancer Continuous Biology Distant Recurrence at 10 Years RS 30 = 20% risk of distant recurrence at 10 years Recurrence Score LOW RECURRENCE SCORE DISEASE Indolent Hormone Therapy Sensitive Minimal, If Any, Chemotherapy Benefit HIGH RECURRENCE SCORE DISEASE Aggressive Hormone Therapy Insensitive Large Chemotherapy Benefit Paik S, et al. N Engl J Med. 2004;351:2817; Paik S, et al. J Clin Oncol. 2006;24:3726; Habel LA, et al. Breast Cancer Res. 2006;8:R25.

11 Oncotype DX® Clinical Validation: NSABP B-14
Objective: Prospectively validate the Recurrence Score® result as a predictor of distant recurrence in node-negative, ER+ patients Multicenter study with prespecified 21-gene assay, algorithm, endpoints, analysis plan Placebo—not eligible Randomized Tamoxifen—eligible Registered Tamoxifen—eligible Main point: A study was performed to clinically validate the prespecified 21-gene RT-PCR assay and Recurrence Score® algorithm as a predictor of the prospectively defined primary endpoint of distant recurrence-free survival in node-negative, estrogen receptor–positive patients treated with tamoxifen from the large multicenter NSABP Study B-14.1 The study protocol also defined the prespecified endpoints and analysis plan. The laboratory was blinded to the clinical outcomes. NSABP B-14 trial (original): 2800 N–, ER+ women were randomized 1:1 to tamoxifen or placebo in double-blind fashion between 1982 and An additional 1235 patients were registered to tamoxifen in the 10-month period following closure of the trial in 1988, making 2617 tamoxifen-treated women available.1 Paik S, Shak S, Tang G, et al. Use of an RT-PCR assay to predict the likelihood of breast cancer recurrence in node-negative, estrogen receptor–positive, tamoxifen-treated patients. In preparation. Paik S, et al. N Engl J Med. 2004;351:

12 Oncotype DX® Clinical Validation: NSABP B-14, Distant Recurrence
Distant recurrence over time 100% 10-Year rate of recurrence = 6.8%* 95% CI: 4.0%, 9.6% 90% 80% 10-Year rate of recurrence = 14.3% 95% CI: 8.3%, 20.3% 70% 60% 10-Year rate of recurrence = 30.5%* 95% CI: 23.6%, 37.4% Proportion without distant recurrence 50% 40% All Patients, n = 668 RS < 18, n = 338 30% 20% RS 18-30, n = 149 Main point: The Oncotype DX® assay is clinically validated to predict the risk of distant recurrence at 10 years in patients with ER+, node-negative breast cancer treated with tamoxifen. The Recurrence Score® result was calculated for each patient: 51% of the patient population fell into the low-risk group (n = 338), 22% fell into the intermediate-risk group (n = 149), and 27% fell into the high-risk group (n = 181).1 This graph demonstrates the difference in distant relapse-free survival (DRFS) over time for the different risk categories. The DRFS for the high- and low-risk groups were statistically significantly different; the 10-year distant relapse-free survival for the low-risk category was 93% compared to 69% for the high-risk category.1 Paik S, Shak S, Tang G, et al. Use of an RT-PCR assay to predict the likelihood of breast cancer recurrence in node-negative, estrogen receptor–positive, tamoxifen-treated patients. In preparation. 10% RS ≥ 31, n = 181 P < 0.001 0% 2 4 6 8 10 12 14 16 RS, Recurrence Score® result Years *10-Year distant recurrence comparison between low- and high-risk groups: P < 0.001 Paik S, et al. N Engl J Med. 2004;351:

13 Oncotype DX® Clinical Validation: NSABP B-20
Objective: Prospectively determine the relationship between Recurrence Score® result and chemotherapy benefit in node-negative, ER+ patients Multicenter study with prespecified 21-gene assay, algorithm, endpoints, analysis plan Tam + MF Randomized Tam + CMF Tam Main point: The objective of this additional study of the NSABP B-20 patients was to determine the magnitude of the chemotherapy benefit with MF (methotrexate, and fluorouracil) or CMF (cyclophosphamide, methotrexate, and fluorouracil) as a function of the 21-gene Oncotype DX® assay. Patients who were randomized in NSABP B-20 to tamoxifen or to tamoxifen plus either CMF or MF chemotherapy were eligible. The primary analysis was prespecified to compare the tamoxifen-treated patients with both chemotherapy arms combined. In secondary prespecified analyses, similar results were seen when the patients treated with CMF (insert) or with MF were examined separately. The analysis by NSABP shows the B-20 study subjects included in this study were similar to all B-20 patients in the cohort and the loss of cases was principally due to blocks never being collected. Fisher B, Dignam J, Wolmark N, et al. J Natl Cancer Inst.1997;89: Paik S, Shak S, Tang G. Expression of the 21 genes in the Oncotype DX® assay and prediction of clinical benefit from tamoxifen in NSABP study B-14 and chemotherapy in NSABP study B- 20. SABCS Abstract #24. 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: Paik S, et al. J Clin Oncol. 2006;24:

14 High Recurrence Score® Result Correlates with Greater Benefit from Chemotherapy (NSABP B-20)
1.0 0.9 Patients with high RS 28% absolute benefit from tamoxifen + chemotherapy 0.8 0.7 0.6 Proportion without distant recurrence 0.5 N Events N Events All patients Tamoxifen + chemotherapy Tamoxifen 424 227 33 31 P = 0.02 4.4% absolute benefit from tamoxifen + chemotherapy 0.4 0.3 RS < 18 Tamoxifen + chemotherapy Tamoxifen 218 135 8 4 P = 0.61 0.2 RS 18-30 Tamoxifen + chemotherapy Tamoxifen 89 45 9 4 P = 0.39 0.1 RS ≥ 31 Tamoxifen + chemotherapy Tamoxifen 117 47 13 18 P < 0.001 2 4 6 8 10 12 Years RS, Recurrence Score result Paik S, et al. J Clin Oncol. 2006;24:

15 Clinical Experience Supports Findings from NSABP B-14 and NSABP B-20
RS Groups by Patient Age <50 yrs (n=367) RS Groups by Tumor Grade Grade 1 (n=277) ≥50 yrs (n=1497) Grade 2 (n=964) RS Groups by Tumor Size ≤2 cm (n=1447) Grade 3 (n=289) Main point: Real world experience with 1,864 node negative patients from the Clallit and Maccabi healthcare systems in Israel supports previous findings from the NSABP B-14 and B-20 studies. Mainly, across age, tumor size and tumor grade, one finds a wide distribution of Recurrence Score results. >2 cm (n=402) Not all grade 1 tumors have low RS values. Only 31% of grade 3 tumors have high RS values. Small tumors have proportionately fewer high RS values. However, there is a range of RS values across both categories of tumor size. Liebermann N, et al. ASCO Abstract 632 (poster presentation).

16 The Oncotype DX® Assay The Only Multi-gene Assay Incorporated into all Major Guidelines to Predict Adjuvant Chemotherapy Benefit in ER+, HER2- EBC NCCN Guidelines® > 0.5 cm, node negative, N1mi Quantifies risk of recurrence as a continuous variable and predicts responsiveness to both tamoxifen and chemotherapy1 Predicts the risk of recurrence and may be used to identify patients likely to benefit from tamoxifen or chemotherapy2 ASCO® Guidelines Node negative Provides additional prognostic and/or predictive information to complement pathology assessment and to predict response to adjuvant chemotherapy4 ESMO Node negative Provides not only prognostic but also predictive information regarding the utility of cytotoxic therapy in addition to endocrine therapy3 St Gallen Consensus Node negative, node positive GHI10087_1013 Recommended as an option for guidance of chemotherapy decisions in patients at intermediate risk* of distant recurrence4 NICE Node negative 1 NCCN Practice Guidelines in Oncology. V 2 Harris L, et al. J Clin Oncol 3 Goldhirsch A, et al. Ann Oncol 4 NICE Diagnostics Guidance ASCO is a trademark of the American Society of Clinical Oncology. NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network. The guidelines do not endorse products or therapies. *Intermediate risk of distant recurrence is defined as NPI score ≥ 3.4 or at intermediate risk by other decision making tools or protocols 4 NICE Diagnostics Guidance 3 Goldhirsch A, et al. Ann Oncol 2 Harris L, et al. J Clin Oncol 1 NCCN Practice Guidelines in Oncology. V

17 Oncotype DX test funding in England
Recommended by NICE Oncotype DX is recommended as an option for guiding adjuvant chemotherapy decisions for people with oestrogen receptor positive (ER+), lymph node negative (LN−) and human epidermal growth factor receptor 2 negative (HER2−) early breast cancer if: The person is assessed as being at intermediate risk and Information on the biological features of the cancer provided by Oncotype DX is likely to help in predicting the course of the disease and would therefore help when making the decision about prescribing chemotherapy Progressing through NHS England, policy document out for comment by 14 March Intermediate risk defined as an OS benefit of >3% with Predict tool Registration of patients and collection of information required by NHS England

18 Which Patients may Benefit from the Oncotype DX® Test?
Clinical indication NICE guidance Use of the Oncotype DX® breast cancer assay in the N+ setting validated for post-menopausal patients ER: Oestrogen receptor HER2: Human Epidermal Growth Factor Receptor 2 NICE guidance DG10. Accessed 14 Jan 2014

19 Treatment decision changed in 26.8% of patients after Oncotype DX®
Holt study (n=142), N0,1 ER+, EBC patients 14.1% Chemo + Hormonal Therapies 85.9% Hormonal Therapy 54.4% Chemo + 45.6% Hormonal Treatment Recommendation with Recurrence Score Report Pre-Recurrence Score® Recommendation 40.1% Chemo + Hormonal Therapies 59.9% Hormonal Therapy Only Chemotherapy No Chemotherapy Analysis based on 142 ER+ N- and N+ (micrometastatic) invasive breast cancer patients Holt S et al. BJC 2013

20 Retrospective Budget Impact Analysis on the use of the Oncotype DX test in Ireland
Estimation of real life budget impact associated with use of the Oncotype DX test in Irish clinical practice during the first year of reimbursement (October Sept 2012) Number of pts tested and no pts receiving CT 75% pts tested were not given CT All pts with a low RS and 57% pts with an intermediate RS avoided CT In first year of reimbursement, ODX test was associated with savings of €856,440 to the chemotherapy budget No of pts Hospitals Falahee M et al St Gallen Breast Cancer Congress 2013

21 Conclusions Oncotype DX® is a consistent and effective test that compliments current decision making tools Recommended in all major international treatment guidelines The Recurrence Score® cannot be predicted by standard clinico-pathological data 31.9% change in treatment recommendations Oncotype DX® was shown to be consistently cost effective across different countries and is expected to generate cost savings

22 Conclusions Despite the use of traditional markers, a proportion of patients are classified as intermediate risk and in whom treatment decisions are not clear Recurrence Score® results reflects individual tumor biology The risk of distant recurrence or chemotherapy benefit can't be accurately predicted by relying on conventional tools alone Oncotype DX the only assay that has been demonstrated to be predictive of likelihood of benefit from chemotherapy allowing chemotherapy to be given to those most likely to benefit2,3 (Level I Evidence) Only assay incorporated into ASCO®, NCCN® , ESMO, St Gallen and NICE guidelines Oncotype DX® was shown to be consistently cost effective across and is expected to generate cost savings Main point: The Oncotype DX® assay quantitatively predicts the likelihood of recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy in women with newly diagnosed, early stage invasive breast cancer. It is the only multi-parameter gene expression assay to show clinical utility in breast cancer, meaning that it has been shown to alter treatment decisions in a significant number of cases. It is the only multivariate genomic classifier recommended in both ASCO, NCCN and St Gallen’s clinical practice guidelines. Harris L, et al. J Clin Oncol. 2007;33(25): NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. v ASCO is a trademark of the American Society of Clinical Oncology and NCCN is a trademark of the National Comprehensive Cancer Network. ASCO and NCCN do not endorse any therapy or product. 1. Harris L, et al. J Clin Oncol. 2007;33(25): Paik S, et al. J Clin Oncol. 2006;24: ;, 3. Albain et al. Lancet Oncol 2010; 11: NCCN Practice Guidelines in Oncology. V Goldhirsch A, et al. Ann Oncol NICE Diagnostics Guidance DG

23 Patient Cases

24 Can You Guess the Recurrence Score®?
68 & 69 year-old patients, small node-negative tumors, grade 2 & 3 PATIENT A 68-year-old patient with 1.1-cm tumor Menopausal Status: Postmenopausal Tumor Type: Infiltrating Ductal Carcinoma (IDC) Tumor Size: 1.1 cm ER Status (IHC): Positive PR Status (IHC): Positive HER2/neu Status: Negative Histologic Grade: 2 Lymph Node Status: Negative General Health: Fair ______________________________________ CASE SUBMITTED BY: Victor G. Vogel, MD PATIENT B 69-year-old patient with 1.3-cm tumor Menopausal Status: Postmenopausal Tumor Type: Infiltrating Ductal Carcinoma (IDC) Tumor Size: 1.3 cm ER Status (IHC): Positive (2) PR Status (IHC): Positive (2) HER2/neu Status: Negative (IHC) Histologic Grade: 3 Lymph Node Status: Negative General Health: PS 0 ______________________________________ CASE SUBMITTED BY: Ella Tepper, MD

25 Can You Guess the Recurrence Score®?
68 & 69 year-old patients, small node-negative tumors, grade 2 & 3 PATIENT A RESULTS Clinical Experience Patients with a Recurrence Score of in the clinical validation study had an Average Rate of Distant Recurrence at 10 years of 23% (95% CI: 18%-28%). PATIENT B RESULTS Clinical Experience Patients with a Recurrence Score of in the clinical validation study had an Average Rate of Distant Recurrence at 10 years of 7% (95% CI: 5%-10%).

26 Can You Guess the Recurrence Score®?
45 & 46 year-old patients, small node-negative tumors, grade 2 & 3 PATIENT A 45-year-old patient with 0.9-cm tumor Menopausal Status: Premenopausal Tumor Type: Infiltrating Ductal Carcinoma (IDC) Tumor Size: 0.9 cm ER Status (IHC): Positive (99%) PR Status (IHC): Positive (13%) HER2/neu Status: Negative (1.7 by FISH) Ki-67: 38% Histologic Grade: 2 Lymph Node Status: Negative (0/2 SLNs) ______________________________________ CASE SUBMITTED BY: Barbara Schwartzberg, MD PATIENT B 46-year-old patient with 0.7-cm tumor Menopausal Status: Premenopausal Tumor Type: Infiltrating Ductal Carcinoma (IDC) Tumor Size: 0.7 cm ER Status (IHC): Positive (91%) PR Status (IHC): Positive (99%) HER2/neu Status: Negative (0.7 by FISH) Ki-67: 35% Histologic Grade: 3 Lymph Node Status: Negative ______________________________________ CASE SUBMITTED BY: Barbara Schwartzberg, MD

27 Can You Guess the Recurrence Score®?
45 & 46 year-old patients, small node-negative tumors, grade 2 & 3 PATIENT A RESULTS Clinical Experience Patients with a Recurrence Score of in the clinical validation study had an Average Rate of Distant Recurrence at 10 years of 10% (95% CI: 7%-12%). PATIENT B RESULTS Clinical Experience Patients with a Recurrence Score of in the clinical validation study had an Average Rate of Distant Recurrence at 10 years of 24% (95% CI: 18%-30%).

28 Questions

29 The Oncotype DX® Report Provides Valuable Information Along a Continuum of ER+ Breast Cancer
The Oncotype DX report provides valuable information on: Node-negative prognosis Node-negative predicted chemotherapy benefit Quantitative data on ER/PR/HER2 Node-positive report contains an additional page with prognosis and predicted chemo benefit information specific to node-positive patients As such the report has a separate page for node-positive disease based on the SWOG 8814 study. This page allows you to combine the burden of nodal disease with the Recurrence Score® result and see the potential benefit of adjuvant chemotherapy. Main point: The Oncotype DX® report provides valuable information along a continuum of ER+ breast cancer. Genomic Health, Inc, has pursued an extensive process to develop the Oncotype DX assay and demonstrate its prognostic and predictive value in determining optimal therapy for women along a continuum of ER+ breast cancer, from node- negative to newly diagnosed node-positive disease. The Oncotype DX assay is helpful in predicting which patients will benefit most and least from chemotherapy. Shown in this slide is a sample report illustrating the types of valuable information that is provided by the Oncotype DX assay. Page 1 contains prognostic information for node-negative patients; the Recurrence Score result as a measure of risk of 10-year distant recurrence, validated in the B-14 study. Page 2 contains predictive information concerning chemotherapy benefit for node-negative patients, validated in the B-20 study. Page 3 contains both predictive and prognostic information for newly diagnosed node-positive patients, as validated in the SWOG 8814 study. Page 4 contains quantitative ER, PR, and HER2 single-gene results.

30 The Oncotype DX® Breast Cancer Assay
Quantitatively predicts the likelihood of breast cancer recurrence and assesses the benefit from both hormonal therapy and chemotherapy (Level I Evidence) High and low Recurrence Score® results reflect different intrinsic tumor biology You cannot predict the risk of distant recurrence or chemotherapy benefit by relying on clinical and pathological variables Changes treatment decisions based on traditional measures 37% of time, sparing patients the negative health and QOL impact of unnecessary chemotherapy and resulting in cost savings Only assay incorporated into ASCO®, NCCN® and St Gallen’s clinical practice guidelines Longest history of commercial genomic assays with over 200,000 patients tested worldwide Main point: The Oncotype DX® assay quantitatively predicts the likelihood of recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy in women with newly diagnosed, early stage invasive breast cancer. It is the only multi-parameter gene expression assay to show clinical utility in breast cancer, meaning that it has been shown to alter treatment decisions in a significant number of cases. It is the only multivariate genomic classifier recommended in both ASCO, NCCN and St Gallen’s clinical practice guidelines. Harris L, et al. J Clin Oncol. 2007;33(25): NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. v ASCO is a trademark of the American Society of Clinical Oncology and NCCN is a trademark of the National Comprehensive Cancer Network. ASCO and NCCN do not endorse any therapy or product.


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