the oncotype dx ® assay in the contemporary management of invasive early-stage breast cancer

The Oncotype DX® Assay in the Contemporary Management of

Invasive Early-stage Breast Cancer

Cancer – The Biology Century

• Understanding and treating the underlying tumor biology– Cancer genetic studies demonstrate the transition of basic

research to clinical application (i.e. BRCA testing)

– Targeted cancer therapies developed based on the unique tumor genetic characteristics (i.e. tamoxifen and trastuzumab)

– Sequencing of the human genome

– Gene expression profiling shown to predict clinical outcome

2

Scientific breakthroughs making personalized medicine in cancer a reality

Evaluating Biomarkers for Clinical Use Key Principles

• Does the test deliver what patients, physicians, regulators, and payers need?– Most importantly, tests must be “Fit for Purpose” with evidence

relevant to that specific purpose

– Consistent results across multiple well-designed studies are required to provide evidence for analytic performance, clinical validity, and clinical utility (see Roadmap to Establish Clinical Utility)

– Test must be shown to have value beyond traditional measures

• Has the test been brought to a standardized implementation? And has the evidence which supports its use been obtained in that standardized implementation?

Hayes DF. Am Soc Clin Oncol Ed Book. 2008:30-34. Simon R. J Clin Oncol. 2005;23:7332-7341.

3

Key Questions When Evaluating Genomic Classifiers

4Hayes DF. Am Soc Clin Oncol Ed Book. 2008:30-34. Simon R. J Clin Oncol. 2005;23:7332-7341.

The Oncotype DX® Gene Panel Was Developed from Clinical Trial Evidence

• 250 cancer-related genes were selected based on extensive literature review (candidate-gene approach)

• Genes were analyzed for expression and relapse-free interval correlations across 3 independent studies of 447 breast cancer patients

Study site N Node status ER status Treatment

NSABP B-20, Pittsburgh, PA 233 N– ER+ Tamoxifen (100%)

Rush University, Chicago, IL 78≥ 10 positive

nodes ER+/–Tamoxifen (54%)

Chemotherapy (80%)

Providence St. Joseph’s Hospital, Burbank, CA 136 N+/– ER+/–

Tamoxifen (41%)Chemotherapy (39%)

Paik S, et al. SABCS 2003. Abstract 16. Cobleigh MA, et al. Clin Cancer Res. 2005;11:8623-8631.Esteban J, et al. Proc Am Soc Clin Oncol. 2003;22: abstract 3416.

From these studies, 21 genes were selected

5

The Recurrence Score® Result Uses Key Genes Linked to Critical Molecular Pathways

16 BREAST CANCER RELATED GENES

Paik S, et al. N Engl J Med. 2004;351:2817-2826.

ERPR

Bcl2SCUBE2

GRB7HER2

Ki-67STK15

SurvivinCyclin B1

MYBL2

Stromelysin 3Cathepsin L2

GSTM1

CD68

BAG1

Beta-actin GAPDH RPLPO GUS TFRC

5 REFERENCE GENES

Estrogen Proliferation HER2 Invasion Others

6

The Recurrence Score® Result Assesses Individual Tumor Biology for ER+ Breast Cancer

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-R39.

Dis

tant

recu

rren

ce a

t 10

year

s

Recurrence Score value

40%

35%

30%

25%

20%

15%

10%

5%

0%0 5 10 15 20 25 30 35 40 45 50

LOW RECURRENCE SCORE DISEASEIndolent

Hormone therapy-sensitiveMinimal, if any, chemotherapy benefit

HIGH RECURRENCE SCORE DISEASEAggressive

Less sensitive to hormone therapyLarge chemotherapy benefit

7

Continuous Biology: ER and HER2 Expression as Measured by RT-PCR

HER2+

Triple-negative*

ER+ HER2–

15

14

13

12

11

10

9

8

7

6

2 3 4 5 6 7 8 9 10 11 12 13 14

HER

2 Ex

pres

sion

(rel

ative

to re

f gen

es; l

og2)

ER Expression (relative to ref genes; log2)

*> 94% of these cases are PR–; rarely strongly PR+

N = 10,618

Shak S, et al. Breast Cancer Res Treat. 2006;100(suppl 1): abstract 6118.8

Clinical Validation of the Oncotype DX® Breast Cancer

Assay in Node-Negative Disease

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

Randomized

Registered

Placebo—not eligible

Tamoxifen—eligible

Tamoxifen—eligible

Paik S, et al. N Engl J Med. 2004;351:2817-2826.10

Oncotype DX® Clinical Validation: NSABP B-14, Distant Recurrence

Distant recurrence over time

10-Year rate of recurrence = 6.8%*95% CI: 4.0%, 9.6%

0 2 4 6 8 10 12 14 16Years


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pro

po

rtio

n w

ith

ou

t d

ista

nt

recu

rren

ce

RS < 18, n = 338

RS 18-30, n = 149

RS ≥ 31, n = 181

All Patients, n = 668

P < 0.001

10-Year rate of recurrence = 14.3%95% CI: 8.3%, 20.3%

10-Year rate of recurrence = 30.5%*95% CI: 23.6%, 37.4%

*10-Year distant recurrence comparison between low- and high-risk groups: P < 0.001

RS, Recurrence Score® result

11

All PatientsLow Risk (RS <18)Int Risk (RS 18-30)High Risk (RS ≥31)


Oncotype DX® Clinical Validation: NSABP B-14, Subgroup Analysis by Tumor Grade

224166

4117

296139

8077

148332887

All patients N=668

Well

Moderate

Poor

% Distant Recurrence-free at 10 Years20 40 60 80 100

RS, Recurrence Score 12

Oncotype DX® Clinical Validation: NSABP B-14, Subgroup Analysis by Tumor Size

Size ≤1 cm

Size 1-2 cm

Size 2-4 cm

Size >4 cm

% Distant Recurrence-free at 10 Years

All patients (N=668)All PatientsLow Risk (RS <18)Int Risk (RS 18-30)High Risk (RS ≥31)

20 40 60 80 100

109652717

305149

7284

3414

614

220110

4466

RS, Recurrence Score


13

Oncotype DX® Clinical Validation: NSABP B-14, Subgroup Analysis by Age

Age >60

Age 50-60

Age 40-50

Age <40

All patients (N=668)

% Distant Recurrence-free at 10 Years40 60 80 100

135662940

59161033

301175

6264

173814844

All PatientsLow Risk (RS <18)Int Risk (RS 18-30)High Risk (RS ≥31)

RS, Recurrence Score


14

• 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

Oncotype DX® Clinical Validation: NSABP B-20

Randomized

Tam + MF

Tam + CMF

Paik S, et al. J Clin Oncol. 2006;24:3726-3734.15

High Recurrence Score® Result Correlates with Greater Benefit from Chemotherapy (NSABP B-20)

RS, Recurrence Score result

Pro

po

rtio

n w

ith

ou

t d

ista

nt

recu

rren

ce

Years

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

2 4 6 8 10 120

4.4% absolute benefit from tamoxifen +

chemotherapy

N Events

All patientsTamoxifen + chemotherapyTamoxifen

424227

3331

P = 0.02

RS 18-30Tamoxifen + chemotherapyTamoxifen

8945

94

P = 0.39

RS < 18Tamoxifen + chemotherapyTamoxifen

218135

84

P = 0.61

N Events

RS ≥ 31Tamoxifen + chemotherapyTamoxifen

11747

1318 P < 0.001

PATIENTS WITH HIGH RS28% absolute benefit from tamoxifen + chemotherapy

Paik S, et al. J Clin Oncol. 2006;24:3726-3734.16

High Recurrence Score® Disease Is Chemo-sensitive Whereas Low Recurrence

Score Disease is Not (NSABP B-20)

Recurrence Score vs Distant Recurrence at 10 YearsTam vs Tam + CMF/MF

50%

45%

40%

30%

25%

20%

35%

10%

5%

0%

15%

0 5 10 15 20 25 30 35 40 45 50

Breast Cancer Recurrence Score

Rate: Tam95% Cl: TamRate: Tam + CMF/MF95% Cl: Tam + CMF/MF

Tam

Tam +CMF/MF

Ave

rage

Rat

e of

Dis

tant

Rec

urre

nce

at 1

0 Y

ears

Absolute Benefit of Chemotherapy (CMF/MF) at 10 Yearsby Recurrence Score Group

% D

ecre

ase

in D

ista

nt R

ecur

renc

e at

10

Yea

rs (

mea

n ±

SE

)

50%

40%

30%

20%

10%

0%

-10%

Recurrence Score

< 18(n = 353)

Recurrence Score

18 - 30(n = 134)

Recurrence Score

≥ 31(n = 164)

Node Negative, ER-Positive Breast Cancer Chemotherapy Benefit

17

NSABP B-20: Many Small Tumors Have Intermediate to High Recurrence Score® Disease

Paik S, et al. J Clin Oncol. 2006;24:3726-3734.

33%

20% 19% 23% 21%

46%

N = 110 N = 318 N = 196 N = 24

Rec

urr

ence

Sco

re

≤1 cm 1.1-2 cm 2.1-4 cm >4 cm

Clinical tumor size

0

20

40

60

80

100P=0.001

64% 56% 46%

16% 25% 30%

18

NSABP B-20: Many Younger Patients Have Low Recurrence Score® Disease

P=0.018

41% 24% 28% 19%

14% 21% 22% 21%

44% 55% 50% 60%

N = 63 N = 226 N = 166 N = 196

Rec

urr

ence

Sco

re


19

NSABP B-20: Significant Proportion of High-Grade Tumors Have

Low Recurrence Score® Disease

12% 22% 42%

16% 22% 22%

73% 56% 36%

N = 77 N = 339 N = 163

P < 0.001 P<0.001

5% 12% 61%

12% 24% 19%

83% 64% 19%

N = 119 N = 340 N = 190

Re

cu

rre

nc

e S

co

re

Re

cu

rre

nc

e S

co

re


20

NSABP B-20: The Recurrence Score® Result Is the Strongest Predictor of

Chemotherapy Benefit

Assessable B20 Patients (n = 651)

Variable HR Lower 95% Upper 95% P

Recurrence Score 0.32 0.11 0.94 .038

Age ≥50 yrs 2.02 0.75 5.47 .162

Tumor size >2 cm 1.34 0.49 3.68 .569

Quantitative ER ≥50 1.96 0.73 5.30 .183

Quantitative PR ≥50 1.87 0.70 4.97 .214

Grade sitePoorModerate

0.270.60

0.020.06

3.016.42

.284

.672

Grade, pathologist APoorModerate

0.731.04

0.190.23

2.894.58

.657

.963

Grade, pathologist BPoorModerate

0.320.36

0.060.06

1.772.03

.192

.244


21

Oncotype DX® Node-Negative Clinical Experience

Clinical Experience Supports Findings from NSABP B-14 and NSABP B-20

RS Groups by Patient Age

RS Groups by Tumor Size

RS Groups by Tumor Grade

Liebermann N, et al. ASCO 2011. Abstract 632 (poster presentation).

<50 yrs (n=367)

≥50 yrs (n=1497)

≤2 cm(n=1447)

>2 cm(n=402)

• Small tumors have proportionately fewer high RS values.

• However, there is a range of RS values across both categories of tumor size.

• Not all grade 1 tumors have low RS values.• Only 31% of grade 3 tumors have high RS

values.

Grade 1(n=277)

Grade 2(n=964)

Grade 3(n=289)

23

Does the Recurrence Score® Impact Treatment Decisions?

Is the Oncotype DX® Assay Cost-Savings and Cost-

Effective?

Meta-Analysis: The Recurrence Score® Result Changes Decisions Across 7 Independent

Decision Impact Studies

Before RS CT + HT HTTotal

After RS CT + HT HT CT + HT HT

Asad et al. 24 36 8 13 81

Henry et al. 6 7 2 14 29

Klang et al. 69 105 20 119 313

Liang et al. 125 85 3 47 260

Lo et al. 20 20 3 40 83

Oratz et al. 19 14 3 32 68

Thanasoulis et al. 8 30 2 38 78

Consistent, large impact of RS on treatment decisions in both directions: •Half of patients initially recommended CT+HT are changed to HT only•Some patients initially recommended HT alone have CT added upon being informed of “High RS Disease”

Asad J, et al. Am J Surg. 2008;196:527-529; Henry LR, et al. J Surg Oncol. 2009;99:319-323; Klang SH, et al. Value Health. 2010;13:381-387; Liang H, et al. SABCS 2007: Abstract 2061; Lo SS, et al. J Clin Oncol. 2010;28:1671-1676; Oratz R, et al. J Oncol Pract. 2007;3:182-186; Thanasoulis T, et al. Am Soc Br Surg Annual Meeting 2008. Hornberger J, et al. SABCS 2010. Poster P2-09-06.

RS, Recurrence Score® result; CT, chemotherapy; HT, hormone therapy N = 912 patients

25

Meta-Analysis: Overall Impact of Recurrence Score® on Treatment Decisions

Treatment plan prior to Oncotype DX®

Treatment plan after RS

Treatment plan after RS

CT + HT

HT

Overall, the RS led to a 37% change in treatment decisions•33% from CT + HT HT•4% from HT CT + HT

4% change 33% change

Hornberger J, et al. SABCS 2010. Poster P2-09-06.

RS, Recurrence Score result26

Most Patients Were Positively Influenced by the Recurrence Score® Result

* Those not satisfied noted a negative impact on QOL, treatment side effects including aches, hot flashes, pain, mood alteration, and negative impact on self image.

*

Lo SS, et al. SABCS 2008. Abstract 3113. [poster presentation]27

N= 89 patients

In addition, the Recurrence Score result helped reduce patients’ anxiety and decisional conflict

The Oncotype DX® Assay Reduces Unnecessary Treatment and is Cost Saving

• Studies show net savings up to $2,000 per patient tested with Oncotype DX1,2

• Saves patients the negative health and QOL impact of unnecessary chemotherapy3

• A reduction in chemotherapy use of approximately 30%, as observed in the Hornberger meta-analysis4, results in $195,000 savings per 100 patients tested annually5

1. Hornberger J, et al. Am J Manag Care. 2005;11:313-324.2. Horberger J, et al. J Oncol Pract 2011; 7: e38S-e45S.

3. Lo SS, et al. J Clin Oncol. 2010;28:1671-1676. 4. Hornberger J, et al. SABCS 2010. Poster P2-09-06.

5. Data on file.28

Oncotype DX® Testingin Node-Positive Disease

Validity of the Oncotype DX® Assay Consistently Demonstrated in Node-Positive

Patients

1. Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834. 2. Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.3. Goldstein LJ, et al. J Clin Oncol. 2008;26:4063-4071.

Study Type Nodal status No. of patients

TransATAC1

Prospective Tam vs

anastrozole

Node positiveNode negative

1231

SWOG 88142

Prospective Tam vs

CAF → TamNode positive 367

ECOG 21973 Prospective AC vs AT

Node positiveNode negative

465

30

Total N+ patients in all three studies =905

Trans ATAC Study Overview

• Secondary analyses:– Determine whether the relationship between continuous Recurrence Score® result and

time to distant recurrence differs by nodal status or treatment arm– Determine the relationship of predefined Recurrence Score groups with time to distant

recurrence by nodal status and treatment arm– Evaluate whether Recurrence Score result adds to the Adjuvant! Online estimate of risk

Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.

Tamoxifen

Anastrozole

Tamoxifen + Anastrozole

ATAC study population (N = 9366)

(combination arm not examined)

Primary Analysis: To determine whether Oncotype DX® assay significantly adds to a proportional hazards model for time to distant recurrence (age, tumor size, grade, treatment) in node-negative, HR+, patients with no adjuvant chemotherapy

31

Trans ATAC: The Recurrence Score® Value Is a Significant Predictors of Distant Recurrence

(node-negative patients, both treatment arms)

Variable HR (95% CI)* P value

Recurrence Score / 50* 5.25 (2.84, 9.73) < 0.001

Tumor Size: > 2 vs ≤ 2 cm 2.78 (1.70, 4.57) < 0.001

Central grade

Moderate vs Well

Poor vs Well

1.70 (0.75, 3.86)

2.06 (0.82, 5.17)

0.270


Multivariate analysis adjusted for treatment arm and patient age*Hazard Ratio for a 50-point increment in Recurrence Score value

Multivariate analysis confirms that the Oncotype DX® Recurrence Score result as a continuous variable is a highly

significant predictor of time to distant recurrence

32

Trans ATAC: Recurrence Score® Value Is Prognostic in Node-Positive Patients


Recurrence Score

group

Hazard ratio* (95% CI)

High vs Low 2.7 (1.5-5.1)

Int vs Low 1.8 (1.0-3.2)

Node+ (n = 306; both treatment arms)

83%

72%

51%

Years0 1 2 3 4 5 6 7 8 9

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Prop

ortio

n di

stan

t re

curr

ence

-fre

e

N (%) EventsLow 160 (52%) 25Int 94 (31%) 25High 52 (17%) 24

Log-rank P < 0.001

33

Trans ATAC: Rate of Distant Recurrence Increases with Number of Positive Nodes

for All Recurrence Score® Values10

0

9-Ye

ar ri

sk o

f dis

tant

recu

rren

ce (%

)

Recurrence Score

Node negativen = 872

1-3 Positive nodesn = 243

≥ 4 Positive nodesn = 63

010

2030

4050

6070

8090

0 5 10 15 20 25 30 35 40 45 50

95% CI

Mean

Low Recurrence Score suggests a low risk of recurrence for patients with 1-3 positive nodes.

Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.34

Superior disease-free survival and overall survival over 10 years

Tamoxifen × 5 yrs

n = 361

CAF × 6 tamoxifen

n = 566

CAF × 6 + tamoxifenn = 550

SWOG 8814

Patients with samples (n = 666)

RT-PCR obtained (n = 601)•Tamoxifen alone (n = 148)•CAF + T (n = 243)•CAF T (n = 219)

Sample for primary analysis•148 + 219 = 367 (40% of parent trial)

SUB ANALYSIS

SWOG 8814:Oncotype DX® Clinical Validation in Node-Positive Patients

Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.35

SWOG 8814: Recurrence Score® Result Is Prognostic for Node-Positive Patients

(Tamoxifen Arm)

0 2 4 6 8 10 0 2 4 6 8 10

1.00

0.75

0.50

0.25

0.00

1.00

0.75

0.50

0.25

0.00

RS < 18 (n = 55)RS 18-30 (n = 46)

RS ≥ 31 (n = 47)

Stratified log-rank P = 0.017 at 10 years

RS < 18 (n = 55)RS 18-30 (n = 46)

RS ≥ 31 (n = 47)


DFS by risk group (tamoxifen-alone arm)

OS by risk group (tamoxifen-alone arm)

Years since registration Years since registration

10-Year DFS: 60%, 49%, 43% 10-Year OS: 77%, 68%, 51%

RS, Recurrence Score result

Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.36

SWOG 8814: Breast Cancer-Specific Survival of Node-Positive Patients by Treatment and

Recurrence Score® Group

BREAST CANCER-SPECIFIC SURVIVAL BY TREATMENT

10-yr BCSS T: 92% vs CAFT: 87%

RS < 18

0

25

50

75

100

0 2 4 6 8 10

Years since registration

CAF T (n = 91, 10 events)Tamoxifen (n = 55, 4 events)



RS 18-30

0

25

50

75

100

0 2 4 6 8 10





RS ≥ 31

0

25

50

75

100

0 2 4 6 8 10




• No benefit to CAF over time for low Recurrence Score

• Strong benefit to CAF over time for high Recurrence ScoreInteraction P = 0.021

Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.

RS, Recurrence Score result 37

Is the Oncotype DX® Assay Included in Treatment

Guidelines?

Oncotype DX® Is the Only Multigene Expression Assay Incorporated into NCCN®,

ASCO®, and St. Gallen’s Guidelines

Newly diagnosed patients with node-negative, ER+ breast cancer who will receive tamoxifenASCO Guidelines ASCO Guidelines

NCCN GuidelinesNCCN GuidelinesTM TM

St. Gallen ConsensusSt. Gallen Consensus

Consider use in > 0.5 cm, HR+, HER2– diseasepT1, pT2, or pT3; pN0 and pN1mi (≤ 2 mm axillary node metastasis)

Oncotype DX has been shown to predict chemotherapy benefit among patients with

HR+ disease

Harris L, et al. J Clin Oncol. 2007;33(25):5287-5312.Adapted from NCCN Practice Guidelines in Oncology – v.2.2011.Goldhirsch A, et al. Ann Oncol. 2011;22:1736-1747.

ASCO is a trademark of the American Society of Clinical Oncology. NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network. ASCO and NCCN do not endorse any therapy or product.

39

The Oncotype DX® Assay Provides Consistent Results in Over 4,000 Breast Cancer

Patients Studied

Study Design N Nodal status Prognostic Predictive

NSABP B-141 Prospective; tam only 668 Neg YES -

Kaiser Permanente2

Prospective; case-control

790 cases/controls

Neg YES -

NSABP B-143 Prospective; placebo vs tam

645 Neg YESYES

Quantitative ER predicts tamoxifen benefit

NSABP B-204 Prospective; tam ± chemo

651 Neg -YES

RS predicts chemotherapy benefit

ECOG 21975 Prospective; AC vs AT

465 Neg/Pos YES -

SWOG 88146 Prospective; tam ± chemo

367 Pos YESYES

RS predicts chemotherapy benefit

TransATAC7 Prospective;tam vs AI

1231 Neg/Pos YES -

1. Paik S, et al. N Engl J Med. 2004;351:2817-2826.2. Habel LA, et al. Breast Cancer Res. 2006;6:R25-R39. 5. Goldstein LJ, et al. J Clin Oncol. 2008;26:4063-4071. 3. Paik S, et al. J Clin Oncol. 2005;23(16S): abstract 510. 6. Albain KS, et al. Lancet Oncol. 2010;11:55-65. 4. Paik S, et al. J Clin Oncol. 2006;24:3726-3734. 7. Dowsett M, et al. J Clin Oncol. 2010;28:1829-1834.

40

The Oncotype DX® Assay Fulfills Criteria for Level I Evidence

Level of evidence

Category Study design Validation studies available

IA

B

Prospective

Prospective using archived samples

None required

One or more with consistent results

IIB

C

Prospective using archived samples

Prospective / observational

None, or inconsistent results

Two or more with consistent results

III C Prospective / observational

None, or one with consistent results, or inconsistent results

IV-V D Retrospective / observational

Not applicable*

Simon RM, et al. J Natl Cancer Inst. 2009;101:1446-1452.

*Level of evidence IV and V studies will never be satisfactory for determination of medical utility

Proper study design determines strength of results and level of evidence

41

Patient Cases

PATIENT A68-year-old patient with 1.1-cm tumorMenopausal Status: PostmenopausalTumor Type: Infiltrating Ductal Carcinoma (IDC) Tumor Size: 1.1 cmER Status (IHC): PositivePR Status (IHC): PositiveHER2/neu Status: NegativeHistologic Grade: 2Lymph Node Status: NegativeGeneral Health: Fair

______________________________________CASE SUBMITTED BY:

Victor G. Vogel, MD

PATIENT B69-year-old patient with 1.3-cm tumorMenopausal Status: PostmenopausalTumor Type: Infiltrating Ductal Carcinoma (IDC)Tumor Size: 1.3 cmER Status (IHC): Positive (2)PR Status (IHC): Positive (2)HER2/neu Status: Negative (IHC)Histologic Grade: 3Lymph Node Status: NegativeGeneral Health: PS 0


Ella Tepper, MD

Can You Guess the Recurrence Score®?68 & 69 year-old patients, small node-negative tumors, grade 2 & 3

43

PATIENT B RESULTSClinical ExperiencePatients with a Recurrence Score of 11 in the clinical

validation study had an Average Rate of Distant Recurrence

at 10 years of 7% (95% CI: 5%-10%).

PATIENT A RESULTSClinical ExperiencePatients with a Recurrence Score of 34 in the clinical


at 10 years of 23% (95% CI: 18%-28%).


44

PATIENT A45-year-old patient with 0.9-cm tumorMenopausal Status: PremenopausalTumor Type: Infiltrating Ductal Carcinoma (IDC)Tumor Size: 0.9 cmER Status (IHC): Positive (99%)PR Status (IHC): Positive (13%)HER2/neu Status: Negative (1.7 by FISH)Ki-67: 38%Histologic Grade: 2Lymph Node Status: Negative (0/2 SLNs)


Barbara Schwartzberg, MD

PATIENT B46-year-old patient with 0.7-cm tumorMenopausal Status: PremenopausalTumor Type: Infiltrating Ductal Carcinoma (IDC)Tumor Size: 0.7 cmER Status (IHC): Positive (91%)PR Status (IHC): Positive (99%)HER2/neu Status: Negative (0.7 by FISH)Ki-67: 35%Histologic Grade: 3Lymph Node Status: Negative


Barbara Schwartzberg, MD


45

PATIENT A RESULTSClinical ExperiencePatients with a Recurrence Score of 15 in the clinical


at 10 years of 10% (95% CI: 7%-12%).

PATIENT B RESULTSClinical ExperiencePatients with a Recurrence Score of 35 in the clinical


at 10 years of 24% (95% CI: 18%-30%).


46

Conclusions

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

48

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

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.

49

the oncotype dx ® assay in the contemporary management of invasive early-stage breast cancer

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