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The American Journal of Managed Care December 2017
Chronic Disease Outcomes From Primary Care Population Health Program Implementation
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Real-World Economic Value of a 21-Gene Assay in Early-Stage Breast Cancer
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Real-World Economic Value of a 21-Gene Assay in Early-Stage Breast Cancer

Stanley E. Waintraub, MD; Donna McNamara, MD; Deena Mary Atieh Graham, MD; Andrew L. Pecora, MD; John Min, BS; Tommy Wu, BA; Hyun Gi Noh, MSC; Jacqueline Connors, RN, OCN; Ruth Pe Benito, MPH, BS; Kelly Choi, MD; Eric Schultz, BS; & Stuart L. Goldberg, MD
Universal gene expression profiling of patients with stage II breast cancer resulted in outpatient savings of $11,000 (inclusive of testing costs) within 6 months of initiation of medical therapy.
This single-institution retrospective review found that GEP using a 21-gene assay resulted in observed outpatient cost savings during the first 6 months of therapy for women with lymph node–negative, HR-positive, HER2/neu oncogene–negative breast cancer who had stage II cancer or grade 2/3 tumors, inclusive of the cost of the testing (savings of $11,494 and $2394, respectively). By contrast, observed outpatient health expenditures rose for women with stage I or grade 1 disease (by $4505 and $6047, respectively) who underwent GEP testing. Because chemotherapy-treated patients also utilized hospital-based services more frequently, inclusion of hospital costs would have further magnified these findings.

The recurrence risk scores in our series were skewed toward lower risks (52% low, 43% intermediate, and 5% high) and strongly correlated with adjuvant chemotherapy use. This finding was similar to those of a US review in which the proportions of Oncotype Dx-tested women with low, intermediate, and high RS were 51%, 39%, and 10%, which was also associated with adjuvant chemotherapy usage in 11%, 47%, and 88% of patients, respectively.15 The influence of GEP testing on subsequent adjuvant chemotherapy decisions was further supported by the findings of a Canadian study in which 38% of oncologists changed their recommendation from chemotherapy use based on GEP results and only 15% increased chemotherapy use.16 Findings of additional meta-analyses have revealed similar trends in treatment changes.17,18 

Importantly, none of the 236 patients in the Canadian study with grade 1 tumors had a high RS. In our study, none of the women with combined stage I and grade 1 tumors had a high RS determined by Oncotype Dx (0/33), thus negating any clinical benefit of GEP testing and defining a cohort where GEP testing unnecessarily raises costs.16 A survey of oncologists in Ireland found that, in the absence of GEP testing, tumor grade drives decisions, with patients with grade 1 tumors not receiving adjuvant chemotherapy but those with grade 2/3 tumors receiving it. The availability of GEP testing resulted in a reduction of adjuvant chemotherapy usage by 57% in a cohort of 592 patients, resulting in a net savings of almost €800,000 ($2.1 million).19 In a Pennsylvania Cancer Registry review, younger patients (<50 years) accrued cost savings whereas older patients (>65 years) incurred higher healthcare expenditures with GEP testing, potentially indicating clinicians' perceptions of the value of adjuvant chemotherapy according to age.14 

Another GEP assay, the 70-gene signature test (MammaPrint; Agendia Inc, Irvine, California), may also identify women with early-stage HR-positive breast cancer who could have excellent outcomes with hormonal therapy.20 Cost-effectiveness models have found potential cost savings and improved QALY gains with this test, but to our knowledge, real-world data confirmation, such as the current study, is not available.21-23


GEP testing using the Oncotype Dx 21-gene assay resulted in a reduction of observed outpatient costs during the initial 6 months of treatment for patients with stage II or grade 2/3 tumors among those with lymph node–negative, HR-positive, HER2/neu oncogene–negative breast cancer treated at a single institution, but increased costs for patients with stage I or grade 1 tumors. 

Author Affiliations: John Theurer Cancer Center at Hackensack University Medical Center (SEW, DM, DMAG, ALP, SLG), Hackensack, NJ; Cota Inc (ALP, JM, TW, HGN, JC, RPB, KC, ES, SLG), New York, NY.

Source of Funding: This manuscript was funded by Cota Inc. Cota Inc is responsible for the contents of the analysis but has no financial interests in the assay or the study outcome.

Author Disclosures: Dr Waintraub has received lecture fees from Amgen, Bristol-Myers Squibb (BMS), Celgene, and Pfizer, and owns stock in Genomic Health, Allergan, Curis, Exelixis, BMS, Celgene, and Pfizer. Dr Pecora has received a patent from Cota and is a board member and stock owner of Cota and Caladrius. Mr Schultz is a board member and employee of Cota. Dr Goldberg is an employee and stock owner of Cota, has been a consultant and provided expert testimony for Novartis, has received honoraria from Pfizer, and has received lecture fees from Novartis and BMS. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article. 

Authorship Information: Concept and design (SEW, DM, DMAG, ALP, KC, ES, SLG); acquisition of data (JC, RPB, KC, SLG); analysis and interpretation of data (ALP, JM, TW, HGN, KC, SLG); drafting of the manuscript (SEW, DM, DMAG, ALP, JM, TW, HGN, KC, ES, SLG); critical revision of the manuscript for important intellectual content (SEW, DM, DMAG, ALP, TW, HGN, KC, ES, SLG); statistical analysis (JM, TW, HGN, SLG); and provision of patients or study materials (SEW, DM, DMAG, ALP).

Address Correspondence to: Stuart L. Goldberg, MD, John Theurer Cancer Center at Hackensack University Medical Center, 92 Second St, Hackensack, NJ 07601. E-mail:
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