Incorporating Tumor Characteristics to Maximize 21-Gene Assay Utility: A Cost-Effectiveness Analysis

Wang, Shiyi; Chen, Tiange; Dang, Weixiong; Mougalian, Sarah Schellhorn; Evans, Suzanne B.; Gross, Cary P.

doi:10.6004/jnccn.2018.7077

Cited by 27 publications

(28 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Literature reported that only a quarter to a third of the eligible patients in the United States had this assay performed [7,12], and in developing countries, certain controversy remained regarding the applicability of this testing [13]. On another hand, cost-effectiveness analysis demonstrated that the 21-gene RS testing was only associated with lower cost in patients with clinical high-risk [14,15]. Thus, a surrogate for the 21-gene RS testing is needed for those who have no access to this assay, as well as to relieve the heavy financial burden of patients for whom the testing is not cost-efficient [16].…”

Section: Discussionmentioning

confidence: 99%

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

Huang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

Background The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS. Methods We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models. Results A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772–0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781–0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685–0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804–0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. Conclusions We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.

show abstract

Section: Discussionmentioning

confidence: 99%

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

Huang

et al. 2021

J Transl Med

View full text Add to dashboard Cite

show abstract

“…Actually, Oncotype DX® is based, among others, on the expression of 5 genes related to proliferation (namely MKI67, STK15, Survivin, CCNB1 and MYBL2), and the association between both RS and single gene expression with the Ki67 IHC levels has previously been addressed. [20][21][22][23] Since use of Oncotype DX® in routine practice requires important financial resources and its cost-effectiveness has been questioned in the literature, 24,25 especially for low-risk BC patients, Ki67-PS can possibly provide additional information with an inferior burden on National Health System budget.…”

Section: Discussionmentioning

confidence: 99%

Integration of Ki-67 index into AJCC 2018 staging provides additional prognostic information in breast tumours candidate for genomic profiling

et al. 2019

View full text Add to dashboard Cite

BACKGROUND: The Eighth edition of the American Joint Committee on Cancer (AJCC) staging system (2018) for breast cancer (BC) introduced the prognostic stage. Moreover, multigene assessment has been indicated to tailor staging in T1/T2/N0, ER-positive/ HER2-negative BC. However, many National Health Systems do not provide reimbursement for routine testing. The aim of this study was to assess whether Ki67 proliferation index is prognostically relevant for patients' candidacy for molecular testing. METHODS: A retrospective series of 686 ER+/HER2− BC were reclassified using AJCC 2018, and in the group of 521 patients for which AJCC 2018 recommends molecular evaluation, we assessed the prognostic efficacy of a prognostic stage enriched by Ki67 (Ki67-PS), considering Ki67 <20% an alternative to recurrence score <11 provided by Oncotype DX. RESULTS: We found that a group of BCs (35.6%, 58/163) assigned to IB stage by prognostic score were down classified to IA with Ki67-PS. The outcome of these 58 cases overlapped with that of lesions classified as stage IA using prognostic stage, showing a significantly better prognosis compared to IB tumours (HR = 2.79, p = 0.003). CONCLUSIONS: These data suggest that Ki67 may be a reliable marker to enrich the 2018 AJCC prognostic score in BC patients' candidacy for genomic profiling.

show abstract

“…1), we simulated a hypothetical cohort of 60-year-old women, stratified by PREDICT risk, and estimated costs and quality-adjusted life years (QALYs) associated with the 2 strategies over a lifetime horizon. 28 We employed a US-payer perspective and discounted costs and QALYs by 3%. 29 Costs were expressed in 2015 US dollars ($), and the health-related quality-of-life adjustments (ie, the "utility weights") used to estimate QALYs were taken from the literature (see Appendix Table 1 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2019.05.…”

Section: Decision-analytic Modelmentioning

confidence: 99%

“…The AML and CHF health states represent long-term toxicities from chemotherapy. In line with the model used by the National Institute for Health and Care Excellence in the UK, 28,30 this Markov model assumes that a proportion of patients with distant recurrence have previously developed a local recurrence. The model also includes absorbing health states for death from different causes, including breast cancer (BC), AML, CHF, and other causes.…”

Section: Decision-analytic Modelmentioning

confidence: 99%

“…To address the influence these assumptions might exert on cost-effectiveness findings, we first estimated the risk classification distributions by 21-GA for each PREDICT risk group using data on the 2245 patients diagnosed from 2011 to 2013 from the Connecticut Tumor Registry (see Appendix in Supplemental Materials found at https://doi.org/10.1 016/j.jval.2019.05.004). 28,39 Second, we estimated the prevalence of chemotherapy use in the clinical low-, intermediate-, and highrisk groups with and without the use of 21-GA from multiple sources (see Appendix in Supplemental Materials found at https:// doi.org/10.1016/j.jval.2019.05.004). 13,21,39,40 As mentioned earlier, we included a scenario analysis assuming no effect of the 21-GA on chemotherapy prevalence in patients with both low clinical risk and low 21-GA recurrence score.…”

Section: Model Parameters and Assumptionsmentioning

confidence: 99%

See 1 more Smart Citation

A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management

Kunst

Alarid‐Escudero

Paltiel³

et al. 2019

Value in Health

Self Cite

View full text Add to dashboard Cite

The 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor-positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA. Methods: Using value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value. Results: We found that current evidence strongly supports the use of the 21-GA in intermediate-and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value

show abstract

Incorporating Tumor Characteristics to Maximize 21-Gene Assay Utility: A Cost-Effectiveness Analysis

Cited by 27 publications

References 49 publications

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

Integration of Ki-67 index into AJCC 2018 staging provides additional prognostic information in breast tumours candidate for genomic profiling

A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management

Contact Info

Product

Resources

About