Download 150428_Oncotype_prom..

The Oncotype DX® Breast Cancer Assay
21-gene assay individualising treatment options
1
Agenda
2
Genomic Health
•
•
•
•
Founded in 2000
Based in Redwood City, California, USA
European headquarters in Geneva, Switzerland
Oncotype DX® assays
•
•
•
•
Breast (invasive)
DCIS
Prostate
Colon
The world-leading provider of genomic-based
diagnostic assays
3
Oncotype DX® Breast Cancer Assay
• Intended for newly diagnosed patients with early-stage ER+, HER2-, invasive
breast cancer, helping to make the best possible treatment decision for
every patient.
• The ONLY multi-gene assay that quantifies risk of disease recurrence and
likelihood of benefit from chemotherapy.
• The ONLY assay consistently incorporated into the 5 internationally
recognized clinical guidelines (ASCO,NCCN, St. Gallen, ESMO, and NICE ) based
on strong clinical evidence, a high level of standardisation and cost
effectiveness.
• A proven 10 year track record with over
tested worldwide.
4
450,000 patients with breast cancer
Two Important Questions Asked by Patients
Will my cancer come back?
Do I need chemotherapy?
5
Traditional Parameters Used to Inform Treatment
Decisions
Current markers are prognostic,
not predictive, of chemotherapy benefit
• Tumour size
• Grade
• Patient age
• Lymph node status
• ER / PR, HER2, Ki-671
6
1Viale
G et al. JNCI 2008;100:207-212
Population-Based Tools Used to Estimate
Treatment Benefit
Current tools are prognostic,
not predictive, of chemotherapy benefit
• Adjuvant! Online1,2
• Nottingham Prognostic Index1,3
• Predict4
7
1NICE
Diagnostics Guidance 10, 2013; 2Balakrishnan A et al Ann Oncol 2011;22:1461-2; 3Haybittle JL et al
Br J Cancer 1982;45:361-366; 4Wishart GC et al Breast Cancer Res 2010;12:R1
Less than 10% of ER+, HER2-, Invasive Breast
Cancer Patients Benefit from Adjuvant Chemotherapy1
Copyright © American Society of Clinical Oncology
8
1EBCTCG
Lancet 2012;379:432-44
Walgren RA et al. J Clin Oncol 2005;23:7342-49
The Oncotype DX® Breast Cancer Assay
• Determines the expression of
21 specific genes from an individual
patient's tumour
• Prognostic: provides information about
the individual risk of recurrence at 10
years
• Predictive: predicts the likelihood of
benefit of chemotherapy in patients who
will receive endocrine therapy
10
The Recurrence Score® Result Uses Key Genes
Linked to Molecular Pathways
• 16 breast cancer-related genes and 5 reference genes
Proliferation
HER2
Others
Ki67
GRB7
GSTM1
STK15
HER2
CD68
BAG1
Survivin
CCNB1 (cyclin B1)
MYBL2
Invasion
MMP11 (stromelysin 3)
CTSL2 (cathepsin L2)
Oestrogen
Reference
ER
ACTB (β-actin)
PGR
GAPDH
BCL2
RPLPO
SCUBE2
GUS
TFRC
11
Paik S et al. NEJM 2004;351:2817-26
The Recurrence Score® Result Provides a Continuous Score Based
on the Expression Level of Different Genes and Gene Groups
Recurrence
Score®
result
=
+ 0.47 x HER2 group score
– 0.34 x ER group score
+ 1.04 x proliferation group score
+ 0.10 x invasion group score
+ 0.05 x CD68
– 0.08 x GSTM1
– 0.07 x BAG1
Recurrence Score® result (0–100) categories
Low risk
<18
Intermediate risk
≥18 and <31
High risk
≥31
The score captures the continuous biology
12
Paik S et al. NEJM 2004;351:2817-26
The Oncotype DX® Breast Cancer Assay Provides
Individualised Risk of Recurrence
Rate of distant recurrence
at 10 years (%)
Intermediate risk
Low risk
40
High Recurrence Score® result
• Aggressive
• Less sensitive to hormone therapy
• Large chemotherapy benefit
35
Low Recurrence Score®
result
• 50–60% of patients are
classified as low risk1,2
• Indolent
• Hormone therapy sensitive
• Minimal, if any,
chemotherapy benefit
30
25
20
15
10
High risk
Rate
95% confidence interval
5
0
0
5
10
15
20
25
30
Recurrence Score®
13
1Paik
S et al. NEJM 2004;351:2817-26; 2Paik S et al. J Clin Oncol 2006;24:3726-34
35
40
45
50
Oncotype DX® Breast Cancer Assay is Developed
For a Select Group of Patients
Which patients may benefit from the
Oncotype DX® invasive breast cancer assay?
Newly diagnosed early-stage invasive breast cancer
Metastatic or locallyadvanced breast cancer
with 4+ positive nodes
Node-negative, or with
*1 to 3 positive nodes
ER-positive,
HER2-negative
14
*Use of the Oncotype DX® Breast Cancer Assay in N+ setting validated for
post-menopausal patients
HER2-positive
Triple-negative
Which Patients may Benefit from the
Oncotype DX® Assay?
Clinical indication
NICE guidance
Newly diagnosed early-stage invasive breast cancer
Newly diagnosed early-stage invasive breast cancer
Metastatic or locallyadvanced breast
cancer with
4+ positive nodes
Node-negative, or with
*1 to 3 positive nodes
ER-positive,
HER2-negative
15
HER2positive
Triplenegative
*Use of the Oncotype DX® Breast Cancer Assay in N+ setting validated for post-menopausal patients
NICE Diagnostics Guidance 10;2013
Node-negative, ER-positive, HER2-negative
The patient is assessed as being at intermediate risk;
the decision to prescribe chemotherapy remains
unclear, so that information on the biological
features of the cancer provided by the
Oncotype DX assay is likely to help in
predicting the course of the disease
Oncotype DX® Assay is the Only Assay Incorporated in all
5 Major Guidelines Used Internationally
St Gallen
ESMO®
ASCO®
Provides not only
prognostic, but also
predictive, information
regarding the utility of
cytotoxic therapy in
addition to endocrine
therapy1
May be used to gain
additional prognostic
and / or predictive
information to complement
pathology assessment
and to predict response to
adjuvant chemotherapy2
Predicts the risk of
recurrence and may be
used to identify patients
likely to benefit from
tamoxifen or
chemotherapy3
American Society of Clinical
Oncology (ASCO), National
Comprehensive Cancer
Network (NCCN) and ESMO
are trademarks of the
American Society of Clinical
Oncology, National
Comprehensive Cancer
Network and European Society
for Medical Oncology,
respectively.
16
NCCN®
NICE
Quantifies the risk of
recurrence and may be
used to identify patients
likely to benefit
from tamoxifen or
chemotherapy4
Recommended as an
option for guidance of
chemotherapy decisions
in patients at intermediate
risk* of distant recurrence5
*Intermediate risk of distant recurrence defined as Nottingham Prognostic Index score above 3.4,
or being at intermediate risk by other decision-making tools or protocols.
1Goldhirsch A et al. Ann Oncol 2013;24:2206-23; 2Senkus E et al. Ann Oncol 2013;24(suppl6):vi7-23;
3Harris L et al. Clin J Oncol 2007;25:5287-312; 4NCCN Guidelines in Oncology – Breast Cancer
v.3 2014; 5NICE Diagnostics Guidance 10, 2013
National Institute for Health and
Care Excellence (NICE), ASCO,
NCCN, ESMO, and St Gallen
International Consensus panel
do not endorse any product or
therapy.
The Oncotype DX® Breast Cancer Assay is
Extensively Studied With Consistent Results
Prognostication in endocrine-treated node-negative:
•
•
•
•
NSABP B-141 (n=668) – tamoxifen
Kaiser Permanente2 (n=790) – tamoxifen
JBCRG study3 (n=200) – tamoxifen
transATAC4 (n=872) – tamoxifen and anastrozole
Prognostication in endocrine-treated node-positive:
•
•
transATAC4 (n=306) – tamoxifen and anastrozole
SWOG-88145 (n=148) – tamoxifen
Prediction of chemotherapy benefit:
•
•
NSABP B-206 (n=651) – CMF / MF in N0 patients
SWOG-88145 (n=219) – CAF in node positive patients
Supportive studies in taxane versus anthracycline-treated patients:
•
•
•
1Paik
17
ECOG E21977 (n=465) – N0–3 patients
NSABP B-288 (n=1065) – node positive patients
PACS019 (n=530) – node positive patients
S et al. NEJM 2004;351:2817-26; 2Habel LA et al. Breast Cancer Res 2006;8:R25; 3Toi M et al.
Cancer 2010;116:3112-8; 4Dowsett M et al. J Clin Oncol 2010;28:1829-34; 5Albain KS et al. Lancet
Oncol 2010;11:55-65; 6Paik S et al. J Clin Oncol 2006;24:3726-34; 7Goldstein LJ et al. J Clin Oncol 2008;
26:4063-71; 8Mamounas EP et al. ASCO 2012;abstr 1; 9Penault-Llorca F et al. ASCO 2014;poster 11052
The Oncotype DX® Breast Cancer Assay is
Extensively Studied With Consistent Results
Prediction of late recurrences:
•
NSABP B-28 (n=1065) and B-14 (n=668)13
Neoadjuvant chemotherapy studies:
•
•
•
•
Gianni et al1 (n=89)
Chang et al2 (n=72)
Yardley et al3 (n=168)
Pivot et al4 (n=81)
Neoadjuvant endocrine studies:
•
•
Akashi-Tanaka et al5 (n=43)
Masuda et al6 (n=77)
ER / PR / HER2 concordance RT-PCR / IHC / FISH:
•
•
ER / PR7-8
HER29-11
Prediction of tamoxifen benefit:
•
1Gianni
18
Kim et al12 (n=645)
L et al. J Clin Oncol 2005;23:7265-77; 2Chang JC et al. Breast Cancer Res Treat 2008;108:233-40; 3Yardley DA et al.
SABCS 2011;abstr P5-13-09; 4Pivot Xet al EBCC 2014;poster 47; 5Akashi-Tanaka S et al. Breast 2009;18:171-4; 6Masuda
N et al. ASCO 2011;poster 558; 7Baehner FL et al. SABCS 2007;poster P1-07-11; 8Badve SS et al. J Clin Oncol 2008;26:
2473-81; 9Baehner FL et al. J Clin Oncol 2010;28:4300-06; 10Sparano JL et al. ASCO 2008;abstr 13; 11Perez EA
et al. ASCO 2013;abstr 520 ;12Kim C et al. J Clin Oncol 2011;29:4160-7; 13Wolmark N et al. ASCO 2014;poster 11024.
Oncotype DX® Clinical Validation of 10-Year Risk
of Recurrence (NSABP B-14)
1.0
10-year rate of recurrence = 6.8%
Proportion without distant recurrence
0.9
0.8
10-year rate of recurrence = 14.3%
0.7
10-year rate of recurrence = 30.5%
0.6
0.5
0.4
All
patients
N
Events
0.3
RS <18
338
28
RS 18–30
149
25
RS ≥31
181
56
0.2
Will my cancer come back?
0.1
0.0
0
20
Patients with high
Recurrence Score® results:
24% increased risk of distant
recurrence (p<0.001)
2
Paik S et al. NEJM 2004;351:2817-26
4
6
8
Years
10
12
14
16
High Recurrence Score® Result Correlates With Greater
Benefit From Chemotherapy (NSABP B-20)
1.0
Proportion without distant recurrence
0.9
Patients with high
Recurrence Score® results:
28% absolute benefit from
tamoxifen + chemotherapy
0.8
0.7
0.6
0.5
N
Events
All patients
Tamoxifen + chemotherapy
Tamoxifen
424
227
33
31
p=0.02
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
0.4
0.3
<10% absolute
benefit from
tamoxifen +
chemotherapy
p<0.001
0.0
0
21
2
Paik S, et al. J Clin Oncol 2006;24:3726-34
4
6
Years
8
10
12
Do I need chemotherapy?
Individualised Recurrence Score® Result Cannot be
Predicted by Traditional Clinical Parameters
By patient age (years)
NSABP B-20 trial (n=651)1
Recurrence Score® value
100
80
60
40
20
0
41%
24%
28%
19%
14%
21%
22%
21%
44%
55%
50%
60%
<40
(n=63)
Recurrence Score® result:
23
1Paik
While, overall, younger
patients have a higher
risk of recurrence,
there are still patients
with low Recurrence
Score® tumours
S et al. J Clin Oncol 2006;24:3726-3734
40–49
(n=226)
<18
50–59
(n=166)
18–30
>60
(n=196)
>31
Individualised Recurrence Score® Result Cannot be
Predicted by Traditional Clinical Parameters
By clinical tumour size (cm)
NSABP B-20 trial (n-651)1
Recurrence Score® value
100
80
60
40
20
0
16%
25%
30%
33%
20%
19%
23%
21%
64%
56%
46%
<1
(n=110)
1.1–2
(n=318)
Recurrence Score® result:
24
1Paik
Similarly, patients with
larger tumours have a
higher risk of recurrence,
but some patients have
low Recurrence Score®
tumours
S et al. J Clin Oncol 2006;24:3726-3734
<18
46%
2.1–4
(n=196)
18–30
>4
(n=24)
>31
Individualised Recurrence Score® Result Cannot be
Predicted by Traditional Clinical Parameters
By central grade
planB trial (n=1062)1
Recurrence Score® value
100
80
40
20
0
5%
30%
37%
39%
39%
63%
56%
31%
1
Recurrence Score® result:
25
1Gluz
Some patients have low
Recurrence Score®
results but higher tumour
grades…
60
O et al. SABCS 2011;abstr S4-3
2
Central grade
<18
3
18–30
>31
Individualised Recurrence Score® Result Cannot be
Predicted by Traditional Clinical Parameters
By Ki-67
planB trial (n=1062)1
Recurrence Score® value
100
80
40
20
0
3%
26%
38%
44%
59%
30%
Ki-67 20
Ki-67 <20
Recurrence Score® result:
26
1Gluz
…and there is wide
distribution of Recurrence
Score® results across
levels of Ki-67 expression
60
O et al. SABCS 2011;abstr S4-3
<18
18–30
>31
The Recurrence Score® Result Provides Actionable
Information That Impact Clinical Practice in the UK
Treatment recommendation
after receiving Recurrence Score® report
Pre-Recurrence Score®
recommendation
86%
82%
Hormonal
therapy
only
40%
Hormonal
therapy only
60%
ordered
Chemotherapy
and hormonal
therapies
46%
Hormonal
therapy only
27
14%
Chemotherapy and
hormonal therapies
Holt S et al BJC 2013;108:2250-8
54%
Chemotherapy and
hormonal therapies
The Recurrence Score® Result Provides Actionable
Information That Impact Clinical Practice
Pooled analysis of 4 European studies (n=527)
Treatment recommendation
after receiving Recurrence Score® report
Pre-Recurrence Score®
recommendation
82%
82%
Hormonal
therapy
only
18%
Chemotherapy and
hormonal therapies
Hormonal
therapy only
55%
ordered
45%
Chemotherapy
and hormonal
therapies
48%
Hormonal
therapy only
28
Albanell J et al. St. Gallen 2013;poster 138
52%
Chemotherapy and
hormonal therapies
Oncotype DX® Breast Cancer Assay
• Intended for newly diagnosed patients with early-stage ER+, HER2-, invasive
breast cancer, helping to make the best possible treatment decision for
every patient.
• The ONLY multi-gene assay that quantifies risk of disease recurrence and
likelihood of benefit from chemotherapy.
• The ONLY assay consistently incorporated into the 5 internationally
recognized clinical guidelines (ASCO,NCCN, St. Gallen, ESMO, and NICE ) based
on strong clinical evidence, a high level of standardisation and cost
effectiveness.
• A proven 10 year track record with over
tested worldwide.
30
450,000 patients with breast cancer
The Oncotype DX® Assay in Clinical Practice
Logistics of the Oncotype DX® Assay
Patient’s tumour,
FFPE block
or slide
32
Sample sent to
the Genomic
Health® lab
for analysis
The Oncotype DX®
test report is
typically available
7–10 days
after the sample
is received
Shared
decision-making
with the patient
Central State-of-the-Art Laboratory
Central state-of-the-art
laboratory with highly
standardised quality
control processes
Consistent
accuracy and high
reproducibility1 of
test results over time2
33
1Cronin
M et al. Clin Chem 2007;53:1084-91; 2 Baehner FL et al. San Antonio Breast Cancer
Symposium 2011 P1-07-11
The Oncotype DX® Patient Report I
• Example of patient report
for ER+, HER2-, N0,
invasive breast
cancer patient
• The patient report includes
prognostic information:
average rate of distant
recurrence at 10 years
34
The Oncotype DX® Patient Report II
• Example of patient report
for ER+, HER2-, N0,
invasive breast
cancer patient
• The patient report includes
predictive information:
the likelihood of benefit
from additional
chemotherapy
35
The Oncotype DX® Patient Report III
• Example of patient report
for ER+, HER2-, N0,
invasive breast
cancer patient
• The patient report includes
a continuous, quantitative,
single gene report of ER,
PR and HER2
36
Patient Cases
Heterogeneity in Treatment Recommendation Among Breast
Cancer Specialists (n>900) From Over 50 Countries
51–70-year-old patients, tumour size 1–2 cm, high ER expression,
low PR expression, 14–20% Ki67 positive
Node-negative (N0) grade 2 tumour
28%
Node-positive (N1-3) grade 2 tumour
21%
24%
13%
66%
48%
Node-negative (N0) grade 3 tumour
Node-positive (N1-3) grade 3 tumour
3%
12%
21%
19%
60%
85%
Chemotherapy
38
Endocrine treatment alone
*Cancer specialists are likely to request more information in 10–15% of cases before making a
treatment decision (based on 896 simulated patient profiles)
Aapro M et al. EBCC9 2014;poster 24
Request for more information*
39
Summary of the Oncotype DX® Assay for ER+,
HER2-, Early Stage Invasive Breast Cancer Patients
• The only multigene assay with demonstrated information
regarding:
•
•
Prognostication (average rate of distant recurrence at 10-year risk)1
Prediction of chemotherapy benefit2
• Oncotype DX® Breast Cancer Assay can reliably classify
~50% of patients at ‘low risk’ who are unlikely to benefit from
adjuvant chemotherapy1,2
• Oncotype DX® Breast Cancer Assay has been extensively
assessed in 14 studies with over 6000 invasive breast cancer
patients with consistent results (Level I, Category B
evidence)3,4
• The only multigene assay incorporated into 5 major clinical
guidelines (St Gallen, ESMO®, ASCO®, NCCN® and NICE)5-9
1Paik
40
S et al. NEJM 2004;351:2817-26; 2Paik S et al J Clin Oncol 2006;24:3726-34; 3Hornberger J et al. JNCI
2012;104:1068-79; 4Burke E et al. EBCC9 2014;poster 525; 5Goldhirsch A et al. Ann Oncol 2013;24:220623; 6Senkus E et al. Ann Oncol 2013;24(suppl6):vi7-23; 7Harris L et al. Clin J Oncol 2007;25:5287-312;
8NCCN Guidelines in Oncology – Breast Cancer v.3 2014; 9NICE Diagnostics Guidance 10, 2013
Thanks for your attention
Appendix: The Oncotype DX® Patient Report I
• Example of patient report for
ER-+, HER2-, N1-3
invasive breast
cancer patient
• The patient report includes:
•
•
42
Prognostic: average rate of
distant recurrence at 10 years
Predictive: likelihood of
benefit from additional
chemotherapy
Appendix: The Oncotype DX® Patient Report II
• Example of patient report for
ER-+, HER2-, N1-3
invasive breast
cancer patient
• The patient report includes
a continuous, quantitative
single gene report of ER,
PR and HER2
43
Appendix: Endocrine Therapy is Effective for ER+,
HER2- Patients, but is not Sufficient for all Patients
• Substantial benefit of adjuvant tamoxifen therapy in
ER-positive patients (16% gain on the 10-year probability
of distant recurrence compared with no treatment)1
• However, there are still 19% of ER+, HER2-, lymph nodenegative patients treated with surgery and endocrine therapy
who will recur1
44
1EBCTCG.
Lancet 2011;378:771-84
Appendix: Only a Modest Proportion of ER+
Patients Will Benefit From Chemotherapy1
• Most patients remain disease-free following surgery and
hormonal treatment alone2
• Some patients do not receive chemotherapy although they
may benefit3
Breast cancer mortality (%)
40
Control
32.0%
30
20
10
Anthracycline
25.6%
16.7%
12.2%
0
Death rates (% per year: total rate-rate in women
without recurrence) and log-rank analyses1
45
1EBCTCG.
Lancet 2012;379:432-44; 2EBCTCG Lancet 2011;378:771-84; 3 Dignam JJ et al Breast
Cancer Res Treat 2009;116:595-602
5433 women, ER + (86% N+)
RR 0.77 (95% CI 0.69–0.86)
Log-rank 2p<0.00001
10-year gain 6.4% (SE 1.4)
Appendix: The Oncotype DX® Breast Cancer Assay
is Extensively Validated
•
The only test assessed in 14 clinical trials with over 6000 invasive
breast cancer patients (Level I, Category B evidence)1,2
•
Consistency of results across studies has been validated in a
meta-analysis3
Study
Design
Nodal
status
Prognostic
Predictive
References
NSABP B-14
(n=668)
Prospective (tam only)
N0
YES
-
Paik S et al.
NEJM 2004
NSABP B-20
(n=651)
Prospective
(tam ± chemo)
N0
-
YES
RS predicts chemotherapy benefit
Paik S et al.
J Clin Oncol 2006
Kaiser
Permanente
(n=790)
Prospective (case-control)
N0
YES
-
Habel LA et al.
Breast Cancer Res 2006
ECOG 2197
(n=465)
Prospective (AC vs AT)
N0–3
YES
-
Goldstein LJ et al.
J Clin Oncol 2008
SWOG 8814
(n=367)
Prospective
(tam ± chemo)
N>0
YES
YES
RS predicts chemotherapy benefit
Albain KS et al.
Lancet Oncol 2010
TransATAC
(n=1231)
Prospective (tam vs AI)
N0 and
N>0
YES
-
Dowsett M et al.
J Clin Oncol 2010
NSABP B-28
(n=1065)
Prospective
(tam + AC vs AC-P)
N>0
YES
-
Mamounas EP et al.
ASCO 2012
1Hornberger
46
J et al. JNCI 2012;104:1068-79; 2Burke E et al. EBCC9 2014;poster 525;
JJ & Roth JA. Breast Cancer Res Treat 2013;141:13-22.
Tam, tamoxifen; chemo, chemotherapy; AC, cyclophosphamide;
AT, cyclophosphamide + taxane; AI, aromatase inhibitor; AC-P, ayclophosphamide + paclitaxe
3Carlson
Appendix: Comparison of Oncotype DX® Breast
Cancer Assay With Other Genomic Tests1
Oncotype DX® /
Recurrence Score
PAM50 / Prosigna
/ Risk of Recurrence
Mammaprint
EndoPredict®
IHC4
Breast Cancer
IndexSM
Continuous score
0–100 (RS): L/IM/H risk
(<18/18–30/≥31)
Continuous score
0–100 (RoR ± tumour
size): L/IM/H risk
(<40/41-60/>60 in N0
and <15/16-40/>40
in N1)
Classification
Two groups:
L/H risk
Continuous
score reported
as L/H risk
Three groups:
L/IM/H risk
Continuous score
0–10: L/IM/H risk
Prognosis
YES
YES
YES
YES
YES
YES
Prediction of
endocrine therapy
benefit
YES
NO
NO
NO
NO
YES
Prediction of
chemotherapy
benefit
YES
NO
NO
NO
NO
NO
Guidelines
recommendation
St Gallen2, NCCN3,
NICE4, ASCO5, ESMO6
St Gallen2
(prognostic)a
St Gallen2
(prognostic)b
St Gallen2
(prognostic)c
NO
NO
Level of evidence7
Prognosis: IB
Prediction: IB
Prognosis: IIB
Prognosis: IIC
Prognosis: IB
Prognosis: IIB
• Oncotype DX® assay is both prognostic of disease recurrence and predictive of
hormonal therapy and chemotherapy benefit
• Oncotype DX® assay is endorsed by 5 clinical guidelines
• Oncotype DX® assay provides a continuous score reflecting the individual’s tumour
biology
1Adapted
from Gluz O et al. Breast Care 2013;8:414-22; 2Goldhirsch A et al. Ann Oncol 2011;22:1736-47;
Guidelines in Oncology – Breast Cancer v.3 2014; 4NICE Diagnostics Guidance 10;2013; 5Harris L
et al. J Clin Oncol 2007;25:5287-312; 6Senkus E et al. Ann Oncol 2013;24(suppl6):vi7-23; 7Simon RM et al.
JNCI 2009;101:1446-52;
aagreed by 29% of voting Panel; bagreed by 40% of voting Panel; cagreed by 22% of voting Panel
3NCCN
47
Appendix: The Recurrence Score® Result is
Predictive of Risk of Late Recurrence
5–10 years
Distant recurrence risk (%)
30
Risk group
Low
Intermediate
High
5–15 years
N Events Risk % (CI)
289
13
4.7 (2.8, 8.0)
111
4
4.1 (1.6, 10.6)
97
12 12.6 (7.4, 21.2)
Risk group
Low
Intermediate
High
Log-rank p=0.01
20
N Events
Risk % (CI)
289
18
6.8 (4.4, 10.6)
111
10
11.2 (6.2, 19.9)
97
15
16.4 (10.2, 25.7)
Log-rank p=0.01
16.4
11.2
10
6.8
0
0
•
•
48
6
7
8
9
10
Years
11
12
13
14
15
The Recurrence Score ® result showed a strong, significant association with DR after 5 years in
patients with higher ER expression (ER ≥9.1) (log rank p=0.01)
The association of the Recurrence Score® result with DR after 5 years in patients with higher ER
was significant after adjustment for age, grade and tumour size
Wolmark N et al. ASCO 2014;poster 11024
Appendix: Distribution of Recurrence Score®
Results by Tumour Size and Grade
Tumour size and grade
≤2 cm,
Grade 1
67%
32%
2%
53%
39%
8%
(n=775)
≤2 cm,
Grade 3
48%
25%
21%
79%
(n=29)
>2 cm,
Grade 2
50%
35%
15%
(n=183)
19%
0
41%
20
Recurrence Score® result:
Liebermann N et al. ASCO 2011;poster 632
28%
(n=194)
>2 cm,
Grade 1
>2 cm,
Grade 3
49
(n=247)
≤2 cm,
Grade 2
39%
40
Recurrence Score
<18
18–30
60
80
>31
Appendix: Distribution of Recurrence Score®
Results by Ki67 (IHC) and Nodal Status
Ki67 <10%, N0
63%
34%
3%
44%
53%
3%
65%
35%
38%
46%
16%
50%
42%
8%
41%
47%
13%
Ki67 and nodal status
Ki67 <10%, N mic
Ki67 <10%, N1–3
Ki67 >=10%, N0
Ki67 >=10%, N mic
Ki67 >=10%, N1-3
0
20
Recurrence Score® result:
50
Liebermann N et al. ASCO 2011;poster 632
Liebermann et al. ESMO 2011
40
Recurrence Score
<18
18–30
60
80
>31
50
Appendix: The Oncotype DX® Breast Cancer Assay
Positively Impacts Quality of Life and is Cost Saving
• Long-term clinical and costs evaluation estimates that use of
the Oncotype DX® results in an increased mean life
expectancy of 0.16 years and an increased quality-adjusted
life expectancy of 0.14 years per patient, compared with
current clinical practice1
• Routine use of the Oncotype DX® assay is cost-effective and
cost-saving versus conventional approaches2
• Benefits driven by optimising chemotherapy treatment and
reducing supportive care3,4
• Initial upfront costs offset by reduced hospitalisation due to
chemotherapy toxicity and costs of treatment following
distant recurrence4
51
1Holt
SDH et al SABCS 2011;poster PD06-02; 2Rouzier R et al Breast cancer Res Treat 2013;
139:621-37; 3Lamond NWC et al Expert Rev Pharmacoecon Outcomes Res 2013;13:243-50;
4Paulden M et al Value Health 2013;16:729-39