chemo? no chemo?

Transcription

chemo? no chemo?

CHEMO? NO CHEMO?
The Oncotype DX Breast Cancer Assay
helps you find an answer
®
Oncotype DX helps clarify one of the most difficult treatment questions
by providing an individualized Recurrence Score® result that assesses the
benefit of chemotherapy and the likelihood of breast cancer recurrence.1,2
Do all patients have the same magnitude
of benefit from chemotherapy?
CHEMO?
Landmark NSABP B-20 trial of 651 estrogen receptor–positive
(ER-positive), node-negative breast cancer patients found1:
• The addition of chemotherapy provided only a 4% absolute
benefit, measured as the proportion of patients free of distant
recurrence at 10 years
Proportion of all patients free of distant recurrence at 10 years1
92%
Proportion without distant recurrence
1.0
0.9
0.8
88%
0.7
0.6
0.5
0.4
P =.02
0.3
n
Tam + chemo 424
Tam
227
0.2
0.1
Events
30
26
0.0
0
2
4
6
8
10
12
Years
The Oncotype DX® Breast Cancer Assay is the only test that provides
patients with an individual score validated to predict chemotherapy
benefit and the likelihood of distant recurrence.1-3
2
ABSOLUTE
BENEFIT
% FROM
TAM + CHEMO
4
Providing predictive and prognostic
information for a broad range of patients
NO CHEMO?
The Oncotype DX® Breast Cancer Assay1,2:
• Analyzes the expression of 21 genes
• Predicts chemotherapy benefit
• Indicates the 10-year risk of distant recurrence
Eligible ER-positive breast cancer patients extend along a biologic continuum1,2,4-7
ER-positive, tamoxifen-treated, or AI-treated4
stage i
pT1, N0
included in asco and
nccn guidelines5,6
®
®
pT2-3, N0
stage ii
pT1-3, N1mi* included in nccn guidelines6
pT0-2, N1
stage iii†
pT3, N1
certain node-positive patients4,7
AI=aromatase inhibitor; ASCO=American Society of Clinical Oncology; NCCN=National Comprehensive Cancer Network.
Cancer Network. ASCO and NCCN do not endorse any product or therapy.
*T1b moderate/poorly differentiated or unfavorable features/1c/2/3, N1mi, M0; HER2-negative.
†
Consider patients from a subset of stage IIIa as indicated; not all stage III patients.
The Oncotype DX Breast Cancer Assay is the only multigene expression
assay incorporated in both the ASCO® and NCCN® guidelines.5,6
3
Accurate, precise, and reproducible
CHEMO?
Why RT-PCR was chosen for the Oncotype DX®
Breast Cancer Assay3:
• Precise, accurate, and highly reproducible over a wide dynamic range
• Minimizes variability that may result from:
—Tissue preparation method, type of fixative, and fixation time
—Tumor block age, storage, and variability in preparation
—Sample heterogeneity
• Can be assayed using fixed tissue from core biopsy or surgical
excision samples
Fixed paraffin-embedded tumor sample.
Genomic Health’s® surgical pathologists take additional steps to
ensure accuracy3
• Perform manual microdissection
• Clear sample contaminants
• Enrich for invasive tumor tissue
With a success rate >97% in generating an accurate result,
you can feel confident in the Oncotype DX Breast Cancer Assay.8
4
Helping you find an individualized
answer with genomics
NO CHEMO?
21 genes identified through a rigorous selection process2
• 447 patients with ER-positive and ER-negative, and node-positive and node-negative breast cancer were examined
• 250 breast cancer–associated genes were analyzed
21-gene panel used to develop the Recurrence Score® algorithm2
PROLIFERATION
Ki-67
STK15
Survivin
Cyclin B1
MYBL2
INVASION
Stromelysin 3
Cathepsin L2
ESTROGEN
OTHER
ER
PR
Bcl-2
SCUBE2
GSTM1
CD68
BAG1
HER2
REFERENCE
GRB7
HER2
Beta-actin
GAPDH
RPLPO
GUS
TFRC
16 cancer genes
• Several identified with a consistent and strong statistical
association to breast cancer recurrence
• Others with robust predictive power for chemotherapy benefit
5 reference genes
• Normalize gene expression
• Provide quality control
Gene expression levels determine the Recurrence Score (RS) result2
RS
=
+0.47 ×
–0.34 ×
+1.04 ×
+0.10 ×
+0.05 ×
–0.08 ×
–0.07 ×
HER2 group score
Estrogen group score
Proliferation group score
Invasion group score
CD68
GSTM1
BAG1
5
The proven prognostic utility of the
Oncotype DX Breast Cancer Assay
®
CHEMO?
Validated in
NSABP
B-14
• Prospective analysis on archived tissue2
• 668 patients treated with tamoxifen2
• ER-positive, node-negative2
Rate of distant recurrence at 10 years (%)
10-year rate of distant recurrence was significantly lower
for patients with low Recurrence Score® values2
30.5 %
35
30
95% Cl
23.6%-37.4%
25
14.3 %
20
15
6.8 %
10
ALL
PATIENTS
%= IN STUDY
(n=668)
15
95% Cl
8.3%-20.3%
95% Cl
4%-9.6%
5
0
RECURRENCE
SCORE VALUE <18
LOW
RISK
RECURRENCE
SCORE VALUE 18-30
INTERMEDIATE
RISK
RECURRENCE
SCORE VALUE ≥31
HIGH
RISK
CI=confidence interval.
The majority of patients had low Recurrence Score values2
51%
RS <18
27%
RS ≥31
22%
RS 18-30
Prognostic: any measurement available at the time of diagnosis or surgery
associated with clinical outcome in the absence of systemic adjuvant therapy
or following the standard of care treatment.3
6
Adding critical information to your
treatment decision
NO CHEMO?
Provides significant information about recurrence risk, independent
of age and tumor size (P<.001)2
Multivariate COX analysis2
VARIABLE
HAZARD RATIO
95% CI
P-VALUE
Age at surgery
0.71
(0.48, 1.05)
.08
Clinical tumor size
1.26
(0.86, 1.86)
.23
Recurrence Score®
3.21*
(2.23, 4.61)
<.001
*The hazard ratio for the Recurrence Score is calculated relative to an increment of 50 units.
May predict the magnitude of tamoxifen benefit, as shown in a follow-up
study to NSABP B-14 (n=645)9†
INTERMEDIATE RECURRENCE SCORE VALUE (18-30)
93%
1.0
0.8
LOW RECURRENCE SCORE VALUE (<18)
86%
0.6
0.4
P =.039
Placebo
Tam
0.2
0.0
n
0
2
4
171
142
6
8
Years
10
12
16
14
1.0
80%
0.8
0.6
0.4
n
Placebo
Tam
0.2
0.0
62%
P =.02
0
2
4
85
69
6
HIGH RECURRENCE SCORE VALUE (≥31)
8
10
12
14
16
Years
1.0
70%
69%
0.8
0.6
0.4
P =.82
Placebo
Tam
0.2
0.0
n
0
2
4
99
79
6
8
10
12
14
16
Years
Results should not be used to indicate that tamoxifen should not be given to the high-risk group.3
†
• Patients with high ER scores (and low Recurrence Score values)
saw the largest benefit from treatment with tamoxifen9
7
The proven predictive utility of the
Oncotype DX Breast Cancer Assay
®
CHEMO?
Validated in
NSABP
B-20
• 651 patients treated with tamoxifen or tamoxifen
plus CMF/MF1
• ER-positive, node-negative1
Low Recurrence Score® value (<18); little to no chemotherapy benefit1
97%
96%
1.0
0.9
0.8
0.7
0.6
0.5
0.4
P =.61
0.3
n
Tam + chemo 218
Tam
135
0.2
0.1
Events
8
4
0.0
0
2
4
6
Years
8
10
12
Intermediate Recurrence Score value (18-30); no substantial chemotherapy benefit1*
91%
1.0
0.9
0.8
89%
0.7
0.6
0.5
0.4
P =.39
0.3
Tam + chemo
Tam
0.2
0.1
Events
89
45
9
4
0.0
0
8
n
2
4
6
Years
8
10
12
*Clinically important benefit cannot be excluded.
Helping you predict the benefit of
chemotherapy in node-negative patients
NO CHEMO?
High Recurrence Score® value (≥31); large chemotherapy benefit1
1.0
88%
0.9
ABSOLUTE
BENEFIT
% FROM
TAM + CHEMO
28
0.8
0.7
0.6
60%
0.5
0.4
P<.001
0.3
n
Tam + chemo 117
Tam
47
0.2
0.1
Events
13
18
0.0
0
2
4
6
Years
8
10
12
Absolute increase in proportion free
of distant recurrence (mean ± SE)
Large reduction in 10-year distant recurrence for high-risk patients treated with chemotherapy1
40%
30%
20%
10%
0
-10%
RECURRENCE
SCORE VALUE <18
RECURRENCE
SCORE VALUE 18-30
RECURRENCE
SCORE VALUE ≥31
(n=353)
(n=134)
(n=164)
Predictive: any measurement associated with benefit or lack of
benefit from a particular therapy.3
9
Additional insight may help guide your
treatment decision
CHEMO?
NSABP B-20 trial (n=651)1
Recurrence Score value
100
Recurrence
Score® value
<18
18-30
≥31
80
60
40
41%
24%
28%
19%
20
14%
21%
22%
21%
44%
55%
50%
60%
0
<40
(n=63)
40-49
50-59
(n=226)
(n=166)
≥60
(n=196)
Patient age
P=.018
• Younger patients can have low Recurrence Score values1 • Older patients can have high Recurrence Score values1
100
80
60
40
16%
25%
30%
33%
20
20%
19%
23%
21%
64%
56%
46%
46%
0
≤1 cm
(n=110)
1.1-2 cm
(n=318)
2.1-4 cm
(n=196)
Clinical tumor size
>4 cm
(n=24)
P=.001
• Patients with larger tumors can have low Recurrence Score values1
• Patients with smaller tumors can have high Recurrence Score values1
10
Providing independent, significant data
beyond traditional measures
NO CHEMO?
100
grading by pathologist at local hospital
80
60
40
20
0
12%
16%
22%
22%
42%
22%
73%
56%
36%
WELL
(n=77)
MODERATE
(n=339)
POOR
(n=163)
Tumor grade (site)
100
Recurrence
Score® value
<18
18-30
≥31
P<.001
grading by pathologist at central lab
80
60
40
20
0
5%
12%
12%
24%
61%
19%
83%
64%
19%
WELL
(n=119)
MODERATE
(n=340)
POOR
(n=190)
Tumor grade (central)
P<.001
• Significant proportions of high-grade tumors have low Recurrence Score values1
• Even low-grade tumors can have high Recurrence Score values1
Nearly 1 in 3 adjuvant treatment recommendations
were changed based on the Recurrence Score results
in a decision impact study.10
11
Providing independent recurrence risk
information across a biologic continuum
CHEMO?
Validated in
Trans
ATAC
• 1,231 postmenopausal patients treated with
tamoxifen or Al4
• 1,178 ER-positive, node-positive, and node-negative4
Comparative risks were seen in node-negative patients and patients
with 1 to 3 nodes who had low Recurrence Score® values3,4
100
Mean
95% Cl
9-year risk of distant recurrence (%)
90
4+ POSITIVE
NODES
n=63
(31 EVENTS)
80
70
60
1-3 POSITIVE
NODES
50
n=243
(43 EVENTS)
40
NODENEGATIVE
30
n=872
(72 EVENTS)
20
10
0
0
5
10
15
20
25
30
35
40
45
50
Oncotype DX® is the only multigene expression assay incorporated in the
NCCN® guidelines to help guide chemotherapy treatment decisions
in patients with micrometastases.6
12
Helping you predict the benefit of
chemotherapy in node-positive patients
NO CHEMO?
• 367 postmenopausal patients treated with tamoxifen
or tamoxifen plus CAF7
• HR-positive, node-positive7
Validated in
SWOG
8814
Strong chemotherapy benefit seen only in the high Recurrence Score® value group7
• No substantial benefit in Breast Cancer Specific Survival from anthracycline based
chemotherapy for node-positive patients with lower Recurrence Score values
INTERMEDIATE RECURRENCE SCORE VALUE (18-30)
92%
1.00
Breast cancer−specific survival
LOW RECURRENCE SCORE VALUE (<18)
87%
0.75
0.50
P =.56
0.25
0.0
Tam only
CAF-T
0
2
4
n
Events
55
91
4
10
Years
6
8
10
1.00
81%
0.75
70%
0.50
P =.89
0.25
0.0
Tam only
CAF-T
0
2
4
n
Events
46
57
11
10
Years
6
8
10
HIGH RECURRENCE SCORE VALUE (≥31)
1.00
73%
0.75
0.50
P =.033
0.25
0.0
Tam only
CAF-T
0
2
4
n
Events
47
71
20
18
Years
6
54%
8
10
Half of adjuvant treatment recommendations for node-positive patients were changed
based on the Recurrence Score result in a decision impact survey11
• For 33.3% of patients tested with Oncotype DX®, their treatment was changed from chemotherapy plus hormonal therapy to hormonal therapy alone
• For 9.4% of patients tested with Oncotype DX, their treatment was changed from hormonal therapy alone to chemotherapy plus hormonal therapy
13
The Oncotype DX Breast Cancer report
®
CHEMO?
Page 1 of 3
Genomic Health, Inc.
301 Penobscot Drive
Redwood City, CA 94063 USA
Toll Free Tel 866-ONCOTYPE (866-662-6897)
Worldwide Tel +1 650-569-2080
www.oncotypeDX.com
PATIENT REPORT
Patient/ID: Doe, Jane
Sex: Female
DOB: 01/01/1950
Medical Record/Patient #: 556677771
Date of Surgery: 9/25/2008
Specimen Type/ID: Breast/SURG-0001
BREAST CANCER ASSAY DESCRIPTION
Requisition: R00003G
Order Received: 10/15/2008
Date Reported: 10/23/2008
Client: Community Medical Center
Ordering Physician: Dr. Harry D Smith
Submitting Pathologist: Dr. John P Williams
Submitting Pathologist: Dr. Sally M Jones
Oncotype DX Breast Cancer Assay uses RT-PCR to determine the expression of a panel of 21 genes in tumor tissue.
The Recurrence Score® is calculated from the gene expression results. The Recurrence Score range is from 0-100.
The first page of
the report contains
the individualized
Recurrence Score®
result between 0
and 100.
RESULTS
Breast Cancer
=
Recurrence Score
6
The findings summarized in the Clinical Experience sections of this report are
applicable to the patient populations defined in each section. It is unknown
whether the findings apply to patients outside these criteria.
CLINICAL EXPERIENCE: PROGNOSIS FOR NODE NEGATIVE, ER-POSITIVE PATIENTS
The Clinical Validation study included female patients with Stage I or II, Node Negative, ER-Positive
breast cancer treated with 5 years of tamoxifen. Those patients who had a Recurrence Score of 6
had an Average Rate of Distant Recurrence of
5% (95% CI: 3%-7%)
The following results are from a clinical validation study of 668 patients from the NSABP B-14 study. N Engl J Med 2004; 351: 2817-26.
Recurrence Score vs Distant Recurrence in Node Negative, ER-Positive Breast Cancer Prognosis
Estimate of the
likelihood of
distant recurrence
at 10 years.
Laboratory Director: Patrick Joseph, MD
CLIA Number 05D1018272
This test was developed and its performance characteristics determined by Genomic Health, Inc. The laboratory is regulated under the Clinical Laboratory Improvement
Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing. This test is used for clinical purposes. It should not be regarded as investigational or for
research. These results are adjunctive to the ordering physician's workup.
Online Ordering and Reports Available — Please contact Customer Service at [email protected]
© 2004-2010 Genomic Health, Inc. All rights reserved. Oncotype DX and Recurrence Score are registered trademarks of Genomic Health, Inc.
GHI004 Rev017
• The report also contains predictive information about chemotherapy
benefit, validated in the NSABP B-20 study1
• For node-positive patients, the report also includes both predictive
and prognostic information, as validated in the SWOG 8814 study7
14
Helping to make a more informed decision
with quantitative data
NO CHEMO?
Page 3 of 3
Genomic Health, Inc.
301 Penobscot Drive
Redwood City, CA 94063 USA
Toll Free Tel 866-ONCOTYPE (866-662-6897)
Worldwide Tel +1 650-569-2080
www.oncotypeDX.com
PATIENT REPORT
Patient/ID: Doe, Jane
Sex: Female
DOB: 01/01/1950
Requisition: R00003G
Order Received: 10/15/2008
Date Reported: 10/23/2008
QUANTITATIVE SINGLE GENE REPORT
The Oncotype DX assay uses RT-PCR to determine the RNA expression of the genes below. These results may differ from ER, PR, or HER2
results reported using other methods or reported by other laboratories.1
The ER, PR, and HER2 Scores are also included in the calculation of the Recurrence Score.
ER Score =
Positive
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 to12.5.3
Please note: The Average Rate of Distant Recurrence reported on Page 1 based on the Recurrence Score was determined in patients who
received 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER Score.
PR Score =
Positive
Quantitative ER, PR,
and HER2 scores,
which are highly
concordant with
IHC and FISH3,12,13
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
HER2 Score =
Negative
The HER2 positive cut-off of 11.5 units, equivocal range from 10.7 to 11.4 units, and negative cut-off of < 10.7 units were validated from
concordance studies of 755 samples using the HercepTest™ assay (immunohistochemistry) and another study of 568 samples using the
PathVysion® assay (FISH). The standard deviation for the HER2 score is less than 0.5 units.4
Genomic Health®
accepts all early-stage
breast cancer samples
to help confirm
or clarify ER status
References:
1. ER Score based on quantitative ESR1 expression (estrogen receptor); PR Score based on quantitative PGR expression (progesterone receptor); HER2 Score
based on quantitative ERBB2 expression.
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.
4. ASCO Breast Cancer Symposium 2008 Abstracts #13 by F.L. Baehner et al., and #41 by F.L. Baehner et al.
Laboratory Director: Patrick Joseph, MD
CLIA Number 05D1018272
This test was developed and its performance characteristics determined by Genomic Health, Inc. The laboratory is regulated under the Clinical Laboratory Improvement
Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing. This test is used for clinical purposes. It should not be regarded as investigational or for
research. These results are adjunctive to the ordering physician's workup.
Online Ordering and Reports Available — Please contact Customer Service at [email protected]
© 2004-2010 Genomic Health, Inc. All rights reserved. Oncotype DX and Recurrence Score are registered trademarks of Genomic Health, Inc.
GHI004 Rev017
Sign up now for the Customer Portal at https://online.genomichealth.com:
• Online ordering
• Online results
• Important customer information postings
Call Customer Service at 866-ONCOTYPE to open an account.
15
The Oncotype DX
Breast Cancer Assay
helps you find an answer
®
CHEMO? NO CHEMO?
A personalized approach to breast cancer treatment
• V
alidated through an extensive suite of studies, across a continuum of more than
4,000 ER-positive patients in 13 clinical studies1,2,4,7
• O
nly test incorporated in both the ASCO® and NCCN® guidelines to help guide chemotherapy treatment decisions5,6
• C
linical utility in node-negative and certain node-positive, ER-positive breast
cancer patients1,2,4-7 • C
hanged adjuvant treatment recommendations for a significant proportion of both
node-negative and node-positive patients10,11
• Genomic Health® is committed to making Oncotype DX available to your patients3
—Extensively reimbursed, with more than 95% of privately insured lives and
Medicare beneficiaries covered for the test, as well as expanding coverage in node-positive patients
—Provides numerous services to ease the reimbursement process for you, your staff, and your patients through the Genomic Access Program (GAP)
• Genomic Health is a CLIA-certified, CAP-accredited reference laboratory
Oncotype DX is now available for patients with stage II colon cancer,
expanding Genomic Health’s technology to other cancer types.
For Customer Service, please contact 866-ONCOTYPE (866-662-6897) or e-mail
[email protected] within the United States, and +1-650-569-2028
or e-mail [email protected] outside the United States.
www.oncotypeDX.com
References: 1. Paik S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol. 2006;24(23):3726-3734. 2. Paik S, et al. A multigene assay to predict recurrence
of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-2826. 3. Data on file. Genomic Health, Redwood City, CA. 4. Dowsett M, et al. Risk of distant recurrence using Oncotype DX in postmenopausal primary
breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study. Abstract presented at: 31st Annual San Antonio Breast Cancer Symposium; December 10-14, 2008; San Antonio, TX. Abstract 53. 5. Harris L, et al. American
Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287-5312. 6. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology™:
breast cancer: V.1.2009. http://www.nccn.org. Published December 2, 2008. Accessed December 22, 2009. 7. Albain KS, et al; for The Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene Recurrence
Score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55-65. 8. Anderson JM, et al. Molecular
characterization of breast cancer core biopsy specimens by gene expression analysis using standardized quantitative RT-PCR. Poster presented at: 32nd Annual San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio,
TX. Poster 6021. 9. Paik S, et al. Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. J Clin Oncol. 2005;23(16S)(suppl).
Abstract 510. 10. Lo SS, et al. Prospective multicenter study of the impact of the 21-gene Recurrence Score assay on medical oncologist and patient adjuvant breast cancer treatment selection [published online ahead of print January 11, 2010].
J Clin Oncol. doi:10.1200/JCO.2008.20.2119. 11. Oratz R, et al. Effect of a 21-gene reverse-transcriptase polymerase chain reaction assay on treatment recommendations for patients with lymph node–positive and estrogen receptor–positive
breast cancer. Poster presented at: 32nd Annual San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, TX. Poster 2031. 12. Badve SS, et al. Estrogen- and progesterone-receptor status in ECOG 2197: comparison of
immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol. 2008;26(15):2473-2481. 13. Baehner FL, et al. A Kaiser-Permanente populationbased study of ER and PR expression by the standard method, immunohistochemistry (IHC), compared to a new method, quantitative reverse transcription polymerase chain reaction (RT-PCR). Presented at: 2007 American Society of Clinical
Oncology Breast Cancer Symposium; September 7-8, 2007; San Francisco, CA. Abstract 88.
American Society of Clinical Oncology (ASCO) and ASCO are registered trademarks of ASCO;
National Comprehensive Cancer Network (NCCN) and NCCN are registered trademarks of NCCN. ASCO and NCCN do not endorse any product or therapy.
Genomic Health, Oncotype DX, and Recurrence Score® are registered trademarks of Genomic Health, Inc.
© 2010 Genomic Health, Inc.
All rights reserved.
GHI201
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chemo? no chemo?

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