This is a poster that I presented at the 2010 San Antonio Breast Cancer Symposium in San Antonio. The content examines the risk-benefit profile of gene-expression profile strategies to inform adjuvant chemotherapy decisions in early-stage breast cancer relative to a standard clinical guideline strategy.

1. Risk-Benefit Framework to Evaluate Gene-Expression Profiling in Early-Stage Breast Cancer:
A Decision Model Developed in Collaboration with Stakeholders
Joshua A. Roth and David L. Veenstra
University of Washington, Pharmaceutical Outcomes Research and Policy Program
INTRODUCTION
MODEL
STRUCTURE
&
INPUTS
RESULTS
• The clinical utility of genetic tests is often unknown at time of Proportion
market entry Receiving Adjuvant
Distant
Recurrences
Life Expectancy
Quality-Adjusted
Life Years (QALYs)
Chemotherapy
• There is a lack of standard methods to evaluate the clinical utility MammaPrint® 50.0% 0.117 32.93 29.34
of genetic tests Oncotype Dx® 46.0% 0.110 33.10 29.50
NCCN 92.1% 0.111 33.09 29.41
• Risk-benefit analysis (RBA) methods can be used to inform Base Case Model Results: These results are for a patient with 10-year distant recurrence risk of
decisions, given the limitations noted above1 15% and with a chemotherapy relative risk reduction of 25%.
0.080 0.100
• We applied this approach to evaluate the health outcomes of
different risk stratification strategies to inform adjuvant 0.040
Incremental QALYs
Incremental QALYs
0.096
chemotherapy decisions in early-stage breast cancer 0.000
0.092
Adjuvant Chemotherapy Decision Structure: Patients enter the model after local-regional treatment
-0.040
and choose either a GEP or NCCN guideline strategy to inform their adjuvant chemotherapy decision.
• Clinical Guidelines: Risk stratification based on node status, -0.080
0.088
tumor histology & size 0.084
-0.120
-National Comprehensive Cancer Network (NCCN)
-0.160 0.080
0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.05 0.10 0.15 0.20 0.25 0.30 0.35
• Gene-Expression Profiling (GEP): Risk stratification based on Chemotherapy Relative Risk Reduction Chemotherapy Relative Risk Reduction
genomic signature from a sample of tumor tissue MammaPrint vs NCCN Oncotype Dx vs NCCN
-Oncotype Dx® (21-Gene Signature; 3 Risk Strata: Low, Intermediate, High)
-MammaPrint® (70-Gene Signature; 2 Risk Strata: Low, High) Incremental QALYs by Chemotherapy Relative Risk Reduction Level: Results are for a patient
with an average 10-year distant recurrence rate of 15% if untreated.
METHODS
DISCUSSION
• Interactive RBA model structured to evaluate the comparative
• The base case results show differences between GEP
health outcomes of adjuvant chemotherapy decision strategies
strategies:
based on GEP (Oncotype Dx® or MammaPrint®) and NCCN -Oncotype Dx® is expected to slightly reduce recurrences and
guidelines slightly increase life expectancy and QALYs relative to NCCN
Markov Model Structure: Patients enter the Markov model after they make their adjuvant
chemotherapy decision and are tracked for their lifetime. -MammaPrint® is expected to slightly increase recurrences and
• Users can vary: Chemotherapy relative risk reduction, 10-year slightly decrease life expectancy and QALYs relative to NCCN
distant recurrence rate, age, cohort size, chemotherapy uptake, MammaPrint®
and health state utility values • Differences in recurrences, life expectancy, and QALYs
Low Risk High Risk Reference
vary moderately with changes in chemotherapy
Proportion of Patients in Risk
• Patients: Stage I or II disease, estrogen receptor positive, lymph Stratum
50% 50% 3
relative risk reduction (see figures above)
node negative Proportion with Distant
4.7% 25.3% Imputed
Recurrence by 10 Years
• Overall, the GEP strategies are expected to lead to
• Base case assumes: Oncotype Dx®
very small changes in recurrences, survival, and
-Patients are age 44 at model entry Low Risk
Intermediate
Risk
High Risk Reference QALYs relative to NCCN guidelines
-All patients receive hormone therapy
-No low risk patients receive adjuvant chemotherapy Proportion of Patients in Risk
REFERENCES
54% 21% 25% 2
Stratum
-All intermediate and high risk patients receive adjuvant chemotherapy
Proportion with Distant
3.2% 9.1% 39.5% 2 1Veenstra DL, Roth JA, Garrison LP, Ramsey SD, Burke W. A Formal Risk-Benefit Framework for
Recurrence by 10 Years
• Patients are followed for distant recurrence until death Genomic Tests: Facilitating the Appropriate Translation of Genomics Into Clinical Practice. Genetics in
Medicine. 2010; DOI: 10.1097/GIM.0b013e3181eff533.
NCCN Guidelines
2Paik S. et al. Gene Expression and Benefit of Chemotherapy in Women With Node-
Low Risk High Risk Reference
• Model parameters were derived from GEP validation trials2,3,4 Negative, Estrogen Receptor–Positive Breast Cancer. Journal of Clinical Oncology. 2006; 24
(23): 1-12.
Proportion of Patients in Risk
7.9% 92.1% 4
Stratum 3Buyse M et al. Validation and Clinical Utility of a 70-Gene Prognostic Signature
• Model development was informed by GEP stakeholder Proportion with Distant
for Women With Node-Negative Breast Cancer. Journal of the National Cancer
Institute. 2006; 98(17): 1183-1192.
1.1% 16.2% Imputed
workshops involving: physicians, patients, payers, test Recurrence by 10 Years 4Fisher B et al. Treatment of Lymph-Node-Negative, Oestrogen-Receptor-
developers, and researchers Selected Base Case Model Parameters: Risk stratification and 10-year distant recurrence rate
Positive Breast Cancer: Long-Term Findings from National Surgical
Adjuvant Breast and Bowel Project Randomised Clinical Trials. Lancet.
2004; 364: 858-868.
Supported by Cooperative Agreement No. 1U18GD000005 from the Centers for Disease Control and Prevention. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.