1

The Value of an Intermediate Recurrence Score® Result in

the Oncotype DX® Assay

2

Does an Oncotype DX® Recurrence Score® result in the

intermediate range (18-30) provide value in treatment decision-making?

3

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

4

Intermediate test results are part of the continuous nature of biology

Treatment Decision Test Result Information Type of Test Result

Evaluation of hypertension Level of systolic and diastolic blood pressure

Continuous scale

Evaluation for prostate cancer Level of serum PSA Continuous scale

Evaluation of cholesterol level Level of serum LDL cholesterol Continuous scale

PSA, prostate-specific antigen; LDL, low-density lipoprotein

5

Many factors contribute to treatment decisions for patients of “intermediate” risk

< 100 mg/dL 100-160 mg/dL100-160 mg/dL > 160 mg/dL> 160 mg/dL

LDL cholesterol (measured on a continuous scale)

Low IntermediateIntermediate HighHigh

Risk of cardiovascular event (continuum of risk)

No statintherapy

Statintherapy

Other risk factors for cardiovascular eventOther risk factors for cardiovascular event

• Blood pressureBlood pressure• • Family historyFamily history• • Smoking historySmoking history• • DiabetesDiabetes

6

Many factors weigh into the adjuvant treatment decision in breast cancer

Hormonal therapy only

• Small tumor size• Low tumor grade• Patient old age• Patient co-morbidities• Patient preference• Oncotype DX® Recurrence Score value• Degree of ER expression

• Small tumor size• Low tumor grade• Patient old age• Patient co-morbidities• Patient preference• Oncotype DX® Recurrence Score value• Degree of ER expression

• Large tumor size• High tumor grade• Patient young age• Patient good health• Patient preference• Oncotype DX Recurrence Score value• Degree of ER expression

• Large tumor size• High tumor grade• Patient young age• Patient good health• Patient preference• Oncotype DX Recurrence Score value• Degree of ER expression

Recurrence Score® value 18-30

Chemotherapy + hormonal therapy

Paik S, et al. ASCO. 2005; Abstract 510.

7

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

8

Distribution of Recurrence Score® results in US clinical practice shows that 52% of patients are low-risk

Palmer G, et al. ECCO-ESMO 2009; abstract 194. Data collected between January 2004 and April 2009.

9

Oncotype DX® Recurrence Score® result has prognostic and predictive clinical value

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.

The lower the Recurrence Score value:The lower the Recurrence Score value:• The lower the risk of distant recurrenceThe lower the risk of distant recurrence• The lower the benefit of chemotherapyThe lower the benefit of chemotherapy• The greater the benefit of tamoxifenThe greater the benefit of tamoxifen

The higher the Recurrence Score value:The higher the Recurrence Score value:• The greater the risk of distant recurrenceThe greater the risk of distant recurrence• The greater the benefit of chemotherapy The greater the benefit of chemotherapy

Dis

tant

Rec

urre

nce

at 1

0 Ye

ars

Recurrence Score

10

Clinical validation of the Oncotype DX® assay: Risk groups defined for distant recurrence

16

P < 0.001

Paik S, et al. N Engl J Med. 2004;351:2817.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 2 4 6 8 10 12 14Years

Prop

ortio

n W

ithou

t Dis

tant

Rec

urre

nce

Risk Group n (%)10-Year Rate of Recurrence 95% CI

Low (RS < 18) 338 (51) 6.8% 4.0%, 9.6%

Intermediate (RS 18-30) 149 (22) 14.3% 8.3%, 20.3%

High (RS ≥ 31) 181 (27) 30.5% 23.6%, 37.4%

NSABP B-14

RS, Recurrence Score® result

11

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

12

Myth vs Fact: The Intermediate Recurrence Score® Group

Intermediate Oncotype DX® Recurrence Score value

doesn’t provide any information regarding

a treatment recommendation.

MythMyth

Intermediate Oncotype DX Recurrence Score value does provide information about the likely response

of patients to adjuvant hormonal therapy and

adjuvant chemotherapy.

FactFact

13The Oncotype DX® assay identifies patients for whom

tamoxifen alone may be appropriate therapy (NSABP B-14)

TAMOXIFENTAMOXIFEN

NO SYSTEMIC NO SYSTEMIC TREATMENTTREATMENT

10-Year Absolute Risk BC Death (%) (95% CI)

Tamoxifen benefitTamoxifen benefit

< 18 18-30 ≥ 31

0 5 10 15 20 25 30 35 40

Paik S, et al. ASCO. 2005; Abstract 510.

Tamoxifenbenefit

Recurrence Score® value

14

The Oncotype DX® assay can predict benefit from chemotherapy and tamoxifen (NSABP B-20)

TAMOXIFEN TAMOXIFEN + CHEMO+ CHEMO

TAMOXIFENTAMOXIFEN

10-Year Absolute Risk BC Death (%) (95% CI)

0 5 10 15 20 25 30 35 40

Chemotherapy benefitChemotherapy benefit

< 18 18-30 ≥ 31

Adapted from Paik S, et al. J Clin Oncol. 2006;24:3726.

Recurrence Score® value

15

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

16

Case 1: Should this patient receive adjuvant chemotherapy?

Patient MP (65 years old)Medical History• Compensated congestive heart failure• “Silent” myocardial infarction

4 years ago• Type 2 diabetes well controlled

with oral therapyPhysical Exam• No symptoms climbing 1 flight

of stairs• Healing well from recent lumpectomy

and sentinel node biopsy• Patient anxious and fearful of

breast cancer, wants “strongest chemotherapy”

Characteristic Result

Tumor size 1.8 cm

Tumor grade 1

Lymph nodes 2 sentinel nodes negative

ER/PR status ER+/PR+

HER2 status Negative

Oncotype DX® Recurrence Score® 25

• Patient MP wants to have adjuvant chemotherapy, but her co-morbidities could make chemotherapy a difficult course.

• Could the potential risks of chemotherapy outweigh the benefits?

• Can the Oncotype DX Recurrence Score result be used to inform adjuvant treatment decisions?

17

Case 1: What does the Oncotype DX® Recurrence Score® tell us about this patient?

CLINICAL EXPERIENCECLINICAL EXPERIENCE

RESULTSRESULTS

25Recurrence Score =

Patients with a Recurrence Score of 25 in clinical validation study had an Average Rate of Distant Recurrence at 10 years of 16.2% (95% CI: 12.6%, 19.8%)

18

Case 1: Single-gene results suggest high likelihood of benefit from tamoxifen

QUANTITATIVE HORMONE RECEPTOR ANALYSISQUANTITATIVE HORMONE RECEPTOR ANALYSISThe Oncotype DX assay uses RT-PCR to determine the RNA expression of the hormone receptor genes below. These results may differ from ERor PR results reported using other methods or reported by other laboratories.1

The ER Score and the PR Score are also included in the calculation of the Recurrence Score.

The ER Score positive/negative cut-off of 6.5 units was validated from a study of 761 samples using the 1D5 antibody (immunohistochemistry)and 607 samples using the SP1 antibody (immunohistochemistry). The standard deviation for the ER Score is less than 0.5 units. 2

Clinical Experience:For ER positive breast cancer, the magnitude of tamoxifen benefit increases as the ER Score increases from 6.5 to ≥ 12.5. 3

Please note: The Average Rate of Distant Recurrence reported on Page 1 based on the Recurrence Score was determined in patients whoreceived 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER Score.

11.0

9.1

The PR Score positive/negative cut-off of 5.5 units was validated from a study of 761 samples using the PR636 antibody (immunohistochemistry)and another study of 607 samples using the PR636 antibody (immunohistochemistry). The standard deviation for the PR Score is less than 0.5 units.2

References:1. ER Score based on quantitative ESR1 expression (estrogen receptor); PR Score based on quantitative PGR expression (progesterone receptor).2. ASCO Breast Cancer Symposium 2007 Abstracts #87 by S.S. Badve et al., and #88 by F.L. Baehner et al.3. ASCO Annual Meeting 2005 Abstract #510 by S. Paik et al.

PR Score = Positive

ER Score = Positive

PATIENT REPORTPATIENT REPORTPatient: MPSex: FemaleDOB: 06/17/1944

Requisition: A0000BOrder Received: 02/01/2009Date Reported: 02/13/2008

19

Case 1: Multiple factors to consider in the adjuvant treatment decision

< 18 ≥≥ 31 31

Oncotype DX® Recurrence Score® value (measured on a continuous scale)

Low HighHigh

Distant recurrence (continuum of risk)

Hormonaltherapy

only

Hormonaltherapy

pluschemotherapy

18-3018-30

IntermediateIntermediate

20

Case 1: Low risk of recurrence reduces patient fears

• Upon hearing the results of the Oncotype DX® assay and the predicted 10-year risk of distant recurrence of 16%, Patient MP is reassured and feels more comfortable with hormonal therapy without chemotherapy.

• After discussing the risks and benefits of chemotherapy, she opts for adjuvant hormonal therapy alone.

21

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

22

Both clinicians and patients find the Oncotype DX® assay helped with adjuvant treatment decisions

Parameter % of Respondents

Medical oncologists (N = 16) who:•Reported increased confidence in treatment recommendation•Felt the Recurrence Score® result provided additional information•Felt the Recurrence Score result influenced treatment recommendation

93.893.887.6

Patients (N = 67) who:•Were glad (at 12 months) that they used the Oncotype DX assay•Found assay results easy to understand•Felt the assay influenced treatment decision•Were satisfied with their adjuvant treatment decision

92.589.680.695.5

Lo SS, et al. J Clin Oncol. 2010; 28:1671-1676. Lo SS et al. SABCS 2008: Abstract 3113.

23

The Intermediate Oncotype DX® Recurrence Score® Result

Factors in Medical Decision-making

The Prognostic Value of the Oncotype DX Assay Across All Risk Groups

The Predictive Value of the Oncotype DX Assay Across All Risk Groups

Case 1: Components of a Complex Treatment Decision

The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision

Case 2: Treatment Decision Based on Many Factors

TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

24

Case 2: Is adjuvant chemotherapy the right treatment option for this patient?

Patient JD (54 years old)• Referred to you for adjuvant

treatmentMedical History• Unremarkable• Menopause 4 years agoPhysical Exam• Underwent a lumpectomy for

adenocarcinoma and sentinel node sampling 2 weeks prior

• Healing left breast and axillary wounds

• Otherwise unremarkable• Patient JD is concerned about

recurrence risk but is also fearful of the potentially disruptive effect chemotherapy may have on her life.

Characteristic Result

Tumor size 1.1 cm

Tumor grade 2

Lymph nodes 3 sentinel nodes negative

ER/PR status ER+/PR+

HER2 status Negative

Oncotype DX® Ordered, but results not yet returned

• Does Patient JD need chemotherapy?• What can the Oncotype DX Recurrence Score®

result reveal about her recurrence risk?

25

Case 2: A Recurrence Score® result of 30 is on the high end of the intermediate range

CLINICAL EXPERIENCE

RESULTS

30Recurrence Score =

Patients with a Recurrence Score of 30 in clinical validation study had an Average Rate of Distant Recurrence at 10 years of 20.0% (95% CI: 15.4%, 24.4%)

26

Case 2: Single-gene results suggest low likelihood of benefit from tamoxifen

QUANTITATIVE HORMONE RECEPTOR ANALYSISQUANTITATIVE HORMONE RECEPTOR ANALYSISThe Oncotype DX assay uses RT-PCR to determine the RNA expression of the hormone receptor genes below. These results may differ from ERor PR results reported using other methods or reported by other laboratories.1

The ER Score and the PR Score are also included in the calculation of the Recurrence Score.

The ER Score positive/negative cut-off of 6.5 units was validated from a study of 761 samples using the 1D5 antibody (immunohistochemistry)and 607 samples using the SP1 antibody (immunohistochemistry). The standard deviation for the ER Score is less than 0.5 units. 2

Clinical Experience:For ER positive breast cancer, the magnitude of tamoxifen benefit increases as the ER Score increases from 6.5 to ≥ 12.5. 3

Please note: The Average Rate of Distant Recurrence reported on Page 1 based on the Recurrence Score was determined in patients whoreceived 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER Score.

7.0

6.0

The PR Score positive/negative cut-off of 5.5 units was validated from a study of 761 samples using the PR636 antibody (immunohistochemistry)and another study of 607 samples using the PR636 antibody (immunohistochemistry). The standard deviation for the PR Score is less than 0.5 units.2

References:1. ER Score based on quantitative ESR1 expression (estrogen receptor); PR Score based on quantitative PGR expression (progesterone receptor).2. ASCO Breast Cancer Symposium 2007 Abstracts #87 by S.S. Badve et al., and #88 by F.L. Baehner et al.3. ASCO Annual Meeting 2005 Abstract #510 by S. Paik et al.

PR Score = Positive

ER Score = Positive

PATIENT REPORTPATIENT REPORTPatient: JDSex: FemaleDOB: 05/17/1955

Requisition: A1111BOrder Received: 03/01/2009Date Reported: 03/13/2008

27

Case 2: Multiple factors to consider in the adjuvant treatment decision

< 18 18-30 ≥ 31

Oncotype DX® Recurrence Score® value (measured on a continuous scale)

Low Intermediate High

Distant recurrence (continuum of risk)

Hormonaltherapy

only

Hormonaltherapy

pluschemotherapy

28

Case 2: Recurrence risk and patient characteristics factor into adjuvant chemotherapy decision

• Patient JD understands her Recurrence Score® result of 30 means she has a substantial chance of recurrence of breast cancer in 10 years.

• Because of the tumor grade, her relatively young age, and her good health, Patient JD decides to have adjuvant chemotherapy followed by hormonal therapy.

29

The full range of Oncotype DX® results provides useful information to guide treatment decisions

• The Oncotype DX Recurrence Score® value provides a scientifically validated continuous measure of risk of distant recurrence and magnitude of chemotherapy benefit.

• Even when the Oncotype DX Recurrence Score® value is in the intermediate zone, the assay results provide information that, together with other clinical information, can help guide treatment decisions.

• The Oncotype DX Recurrence Score result allows an individualized assessment of risk and response to therapy, which contributes to making more informed treatment decisions for individual patients.