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
Scientific breakthroughs making personalized medicine in cancer a reality
2
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
Strongly
prognostic?
Accurate
and
reliable?
Predictive of
chemotherapy
benefit?
Fit for
purpose
Incorporated
in treatment
guidelines?
Hayes DF. Am Soc Clin Oncol Ed Book. 2008:30-34.
Simon R. J Clin Oncol. 2005;23:7332-7341.
What is the
level of
evidence?
4
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
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%)
Study site
From these studies, 21 genes were selected
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.
5
The Recurrence Score® Result Uses Key Genes
Linked to Critical Molecular Pathways
16 BREAST 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
5 REFERENCE GENES
Beta-actin
GAPDH
RPLPO
GUS
TFRC
6
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
The Recurrence Score® Result Assesses
Individual Tumor Biology for ER+ Breast Cancer
Distant recurrence at 10 years
CONTINUOUS BIOLOGY
40%
35%
30%
25%
20%
15%
10%
5%
0%
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score value
LOW RECURRENCE SCORE DISEASE
Indolent
Hormone therapy-sensitive
Minimal, if any, chemotherapy benefit
HIGH RECURRENCE SCORE DISEASE
Aggressive
Less sensitive to hormone therapy
Large chemotherapy benefit
7
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.
Continuous Biology: ER and HER2
Expression as Measured by RT-PCR
N = 10,618
15
HER2+
HER2 Expression (relative to ref genes; log2)
14
13
12
11
Triple-negative*
10
9
8
7
ER+ HER2–
6
2
3
4
5
6
7
8
9
10
11
12
13
14
ER Expression (relative to ref genes; log2)
*> 94% of these cases are PR–; rarely strongly PR+
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 nodenegative, ER+ patients
Placebo—not eligible
Randomized
Registered
Tamoxifen—eligible
Tamoxifen—eligible
• Multicenter study with prespecified 21-gene assay,
algorithm, endpoints, analysis plan
10
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
Oncotype DX® Clinical Validation:
Proportion without distant recurrence
NSABP B-14, Distant Recurrence
Distant recurrence over time
100%
10-Year rate of recurrence = 6.8%*
90%
95% CI: 4.0%, 9.6%
80%
10-Year rate of recurrence = 14.3%
70%
95% CI: 8.3%, 20.3%
60%
10-Year rate of recurrence = 30.5%*
95% CI: 23.6%, 37.4%
50%
40%
All Patients, n = 668
30%
RS < 18, n = 338
20%
RS 18-30, n = 149
10%
RS ≥ 31, n = 181
P < 0.001
0%
0
2
RS, Recurrence Score® result
4
6
8
10
14
16
Years
*10-Year distant recurrence comparison between low- and high-risk groups: P < 0.001
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
12
11
Oncotype DX® Clinical Validation:
NSABP B-14, Subgroup Analysis by Tumor Grade
All patients N=668
Well
Moderate
Poor
All Patients
Low Risk (RS <18)
Int Risk (RS 18-30)
High Risk (RS ≥31)
224
166
41
17
296
139
80
77
148
33
28
87
RS, Recurrence Score
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
20
40
60
80
100
% Distant Recurrence-free at 10 Years
12
Oncotype DX® Clinical Validation:
NSABP B-14, Subgroup Analysis by Tumor Size
All patients (N=668)
Size ≤1 cm
109
65
27
17
Size 1-2 cm
305
149
72
84
Size 2-4 cm
220
110
44
66
Size >4 cm
34
14
6
14
RS, Recurrence Score
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
All Patients
Low Risk (RS <18)
Int Risk (RS 18-30)
High Risk (RS ≥31)
20
40
60
80
100
% Distant Recurrence-free at 10 Years
13
Oncotype DX® Clinical Validation:
NSABP B-14, Subgroup Analysis by Age
All patients (N=668)
Age <40
59
16
10
33
Age 40-50
135
66
29
40
Age 50-60
173
81
48
44
Age >60
301
175
62
64
All Patients
Low Risk (RS <18)
Int Risk (RS 18-30)
High Risk (RS ≥31)
40
RS, Recurrence Score
Paik S, et al. N Engl J Med. 2004;351:2817-2826.
60
80
100
% Distant Recurrence-free at 10 Years
14
Oncotype DX® Clinical Validation:
NSABP B-20
•
Objective: Prospectively determine the relationship between
Recurrence Score® result and chemotherapy benefit in node-negative,
ER+ patients
Tam + MF
Randomized
Tam + CMF
Tam
•
Multicenter study with prespecified 21-gene assay, algorithm,
endpoints, analysis plan
15
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
Proportion without distant recurrence
High Recurrence Score® Result Correlates with
Greater Benefit from Chemotherapy (NSABP B-20)
1.0
0.9
0.8
PATIENTS WITH HIGH RS
28% absolute benefit from
tamoxifen + chemotherapy
0.7
0.6
0.5
N
Events
0.4
All patients
Tamoxifen + chemotherapy
Tamoxifen
424
227
33
31
P = 0.02
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
RS ≥ 31
Tamoxifen + chemotherapy
Tamoxifen
117
47
13
18
P < 0.001
0.1
0
2
4
6
8
10
4.4% absolute benefit
from tamoxifen +
chemotherapy
12
Years
RS, Recurrence Score result
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 Years
Tam vs Tam + CMF/MF
50%
Rate: Tam
95% Cl: Tam
Rate: Tam + CMF/MF
95% Cl: Tam + CMF/MF
45%
40%
35%
Tam
30%
25%
20%
15%
Tam +
CMF/MF
10%
5%
0%
0
5
10
15
20
25
30
35
40
Breast Cancer Recurrence Score
45
50
% Decrease in Distant Recurrence at 10 Years (mean ± SE)
Average Rate of Distant Recurrence at 10 Years
Node Negative, ER-Positive Breast Cancer Chemotherapy Benefit
Absolute Benefit of Chemotherapy (CMF/MF) at 10 Years
by Recurrence Score Group
50%
40%
30%
20%
10%
0%
-10%
Recurrence Score
Recurrence Score
Recurrence Score
< 18
(n = 353)
18 - 30
(n = 134)
≥ 31
(n = 164)
17
NSABP B-20: Many Small Tumors Have
Intermediate to High Recurrence Score® Disease
P=0.001
Recurrence Score
100
80
60
40
20
16%
25%
30%
33%
20%
19%
23%
21%
64%
56%
46%
46%
0
N = 110
N = 318
N = 196
N = 24
≤1 cm
1.1-2 cm
2.1-4 cm
>4 cm
Clinical tumor size
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
18
NSABP B-20: Many Younger Patients
Have Low Recurrence Score® Disease
Recurrence Score
P=0.018
41%
24%
28%
19%
14%
21%
22%
21%
44%
55%
50%
60%
N = 63
N = 226
N = 166
N = 196
19
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
NSABP B-20: Significant Proportion of
High-Grade Tumors Have
Low Recurrence Score® Disease
P<0.001
12%
22%
42%
16%
22%
22%
73%
56%
36%
N = 77
N = 339
N = 163
Recurrence Score
Recurrence Score
P < 0.001
5%
12%
61%
12%
24%
19%
83%
64%
19%
N = 119
N = 340
N = 190
20
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
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 site
Poor
Moderate
0.27
0.60
0.02
0.06
3.01
6.42
.284
.672
Grade, pathologist A
Poor
Moderate
0.73
1.04
0.19
0.23
2.89
4.58
.657
.963
Grade, pathologist B
Poor
Moderate
0.32
0.36
0.06
0.06
1.77
2.03
.192
.244
Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
21
Oncotype DX® Node-Negative
Clinical Experience
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
Grade 3
(n=289)
≤2 cm
(n=1447)
>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 2011. Abstract 632 (poster presentation).
23
Does the Recurrence Score®
Impact Treatment Decisions?
Is the Oncotype DX® Assay
Cost-Savings and CostEffective?
Meta-Analysis: The Recurrence Score® Result
Changes Decisions Across 7 Independent
Decision Impact Studies
Asad et al.
CT + HT
Before RS
HT
After RS CT + HT
24
36
HT
CT + HT
HT
8
13
Total
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
RS, Recurrence Score® result; CT, chemotherapy; HT, hormone therapy
N = 912 patients
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.
25
Meta-Analysis: Overall Impact of
Recurrence Score® on Treatment Decisions
Treatment
plan after RS
Treatment plan prior
to Oncotype DX®
12%
88%
4% change
CT + HT
HT
Treatment
plan after RS
48%
52%
33%
change
Overall, the RS led to a 37% change in treatment decisions
• 33% from CT + HT  HT
• 4% from HT  CT + HT
RS, Recurrence Score result
Hornberger J, et al. SABCS 2010. Poster P2-09-06.
26
Most Patients Were Positively Influenced
by the Recurrence Score® Result
Immediately Post-RS
12 Months Later
N= 89 patients
I am glad I took the RS assay
*
RS results were easy to
understand
I think the RS helped support
treatment decision
I would have made the same
treatment decision without RS
I feel the RS influenced my
treatment decision
0
20
40
60
80
100
* 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.
In addition, the Recurrence Score result helped reduce patients’ anxiety and decisional conflict
27
Lo SS, et al. SABCS 2008. Abstract 3113. [poster presentation]
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® Testing
in Node-Positive Disease
Validity of the Oncotype DX® Assay
Consistently Demonstrated in Node-Positive
Patients
Study
Type
Nodal status
No. of patients
TransATAC1
Prospective
Tam vs
anastrozole
Node positive
Node negative
1231
SWOG 88142
Prospective
Tam vs
CAF → Tam
Node positive
367
ECOG 21973
Prospective
AC vs AT
Node positive
Node negative
465
Total N+ patients in all three studies =905
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.
30
Trans ATAC Study Overview
ATAC study population (N = 9366)
Tamoxifen
Anastrozole
Tamoxifen + Anastrozole
(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
• 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
31
Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.
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
0.270
1.70 (0.75, 3.86)
2.06 (0.82, 5.17)
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
Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.
Trans ATAC: Recurrence Score® Value Is
Prognostic in Node-Positive Patients
Node+ (n = 306; both treatment arms)
1.0
Proportion distant
recurrence-free
0.9
0.8
83%
Log-rank P < 0.001
0.7
72%
0.6
51%
0.5
0.4
0.3
N (%)
Low 160 (52%)
Int
94 (31%)
High 52 (17%)
0.2
0.1
0.0
0
1
2
Events
25
25
24
3
4
5
6
7
8
9
Years
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)
33
Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.
90 100
Mean
≥ 4 Positive nodes
n = 63
50
60
70
80
95% CI
30
40
1-3 Positive nodes
n = 243
10
20
Node negative
n = 872
0
9-Year risk of distant recurrence (%)
Trans ATAC: Rate of Distant Recurrence
Increases with Number of Positive Nodes
for All Recurrence Score® Values
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
Low Recurrence Score suggests a low risk of recurrence for patients with 1-3 positive nodes.
34
Dowsett M, et al. J Clin Oncol. 2010;28(11):1829-1834.
SWOG 8814:Oncotype DX® Clinical
Validation in Node-Positive Patients
SWOG 8814
SUB ANALYSIS
Postmenopausal, node-positive,
ER-positive breast cancer
N = 1477
Tamoxifen
× 5 yrs
n = 361
CAF × 6
+ tamoxifen
n = 550
CAF × 6
 tamoxifen
n = 566
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)
Superior disease-free survival
and overall survival over 10 years
35
Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.
SWOG 8814: Recurrence Score® Result Is
Prognostic for Node-Positive Patients
(Tamoxifen Arm)
OS by risk group
(tamoxifen-alone arm)
DFS by risk group
(tamoxifen-alone arm)
1.00
1.00
0.75
0.75
0.50
0.50
Stratified log-rank P = 0.017 at 10 years
0.25
Stratified log-rank P = 0.003 at 10 years
0.25
RS < 18 (n = 55)
RS 18-30 (n = 46)
RS ≥ 31 (n = 47)
0.00
RS < 18 (n = 55)
RS 18-30 (n = 46)
RS ≥ 31 (n = 47)
0.00
0
2
4
6
8
10
0
2
4
6
8
10
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
RS ≥ 31
RS 18-30
RS < 18
100
100
100
75
75
75
50
50
50
Stratified log-rank
P = 0.56 at 10 years
25
Stratified log-rank
P = 0.89 at 10 years
25
CAF  T (n = 91, 10 events)
Tamoxifen (n = 55, 4 events)
25
CAF  T (n = 46, 10 events)
Tamoxifen (n = 57, 11 events)
0
CAF  T (n = 47, 18 events)
Tamoxifen (n = 71, 20 events)
0
0
2
4
6
8
Years since registration
10-yr BCSS
T: 92% vs CAFT: 87%
• No benefit to CAF over time
for low Recurrence Score
RS, Recurrence Score result
Albain KS, et al. Lancet Oncol. 2010;11(1):55-65.
Stratified log-rank
P = 0.033 at 10 years
10
0
0
2
4
6
8
Years since registration
10-yr BCSS
T: 70% vs CAFT: 81%
Interaction P = 0.021
10
0
2
4
6
10
8
Years since registration
10-yr BCSS
T: 54% vs CAFT: 73%
• Strong benefit to CAF over time
for high Recurrence Score
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
NCCN GuidelinesTM
Consider use in > 0.5 cm, HR+, HER2– disease
pT1, pT2, or pT3; pN0 and pN1mi
(≤ 2 mm axillary node metastasis)
ASCO Guidelines
Newly diagnosed patients with node-negative,
ER+ breast cancer who will receive tamoxifen
St. Gallen Consensus
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
-
YES
YES
Quantitative ER predicts
tamoxifen benefit
NSABP
B-143
Prospective; placebo
vs tam
NSABP
B-204
Prospective;
tam ± chemo
651
Neg
-
YES
RS predicts
chemotherapy benefit
ECOG 21975
Prospective;
AC vs AT
465
Neg/Pos
YES
-
88146
Prospective;
tam ± chemo
367
Pos
YES
YES
RS predicts
chemotherapy benefit
Prospective;
tam vs AI
1231
Neg/Pos
YES
-
SWOG
TransATAC7
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.
3. Paik S, et al. J Clin Oncol. 2005;23(16S): abstract 510.
4. Paik S, et al. J Clin Oncol. 2006;24:3726-3734.
645
Neg
5. Goldstein LJ, et al. J Clin Oncol. 2008;26:4063-4071.
6. Albain KS, et al. Lancet Oncol. 2010;11:55-65.
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
A
Prospective
None required
B
Prospective using
archived samples
One or more with consistent
results
B
Prospective using
archived samples
None, or inconsistent results
C
Prospective /
observational
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*
I
II
*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
Simon RM, et al. J Natl Cancer Inst. 2009;101:1446-1452.
Patient Cases
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
PATIENT B
69-year-old patient with 1.3-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
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:
CASE SUBMITTED BY:
Victor G. Vogel, MD
Ella Tepper, MD
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Can You Guess the Recurrence Score®?
68 & 69 year-old patients, small node-negative tumors, grade 2 & 3
PATIENT A RESULTS
Clinical Experience
PATIENT B RESULTS
Clinical Experience
Patients with a Recurrence Score of 34 in the clinical
Patients with a Recurrence Score of 11 in the clinical
validation study had an Average Rate of Distant Recurrence
validation study had an Average Rate of Distant Recurrence
at 10 years of 23% (95% CI: 18%-28%).
at 10 years of 7% (95% CI: 5%-10%).
44
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
PATIENT B
46-year-old patient with 0.7-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)
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:
CASE SUBMITTED BY:
Barbara Schwartzberg, MD
Barbara Schwartzberg, MD
45
Can You Guess the Recurrence Score®?
45 & 46 year-old patients, small node-negative tumors, grade 2 & 3
PATIENT A RESULTS
Clinical Experience
PATIENT B RESULTS
Clinical Experience
Patients with a Recurrence Score of 15 in the clinical
Patients with a Recurrence Score of 35 in the clinical
validation study had an Average Rate of Distant Recurrence
validation study had an Average Rate of Distant Recurrence
at 10 years of 10% (95% CI: 7%-12%).
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
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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