21-gene Testing Research Articles

Response to neoadjuvant chemotherapy and the 21-gene breast recurrence score in young women with estrogen receptor-positive early breast cancer.

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

Prospective observational study on the impact of the 21-gene assay on treatment decisions and resources optimization in breast cancer patients in Lombardy: The BONDX study

PurposeAdjuvant treatment decisions in early breast cancer (eBC) have traditionally been driven by risk stratification based on clinical and pathological risk factors. The 21-gene Oncotype DX® assay has been validated as a predictive test for benefit from adjuvant chemotherapy (CT), hence assessing its impact in clinical decisions is of high interest. The objective of this study was to estimate the rate of adjuvant treatment decision modification impacted by the Recurrence Score® result, and the consequent budget impact. MethodsThe study was a multicentre, prospective, real-life experience in Lombardy (Italy) including consecutive patients with T1–T3, N0–N1a, and ER+/HER2-eBC with clinical-pathologic “intermediate risk” of relapse. The change in treatment recommendations was assessed before and after availability of Recurrence Score result. A budget model evaluated the implications of 21-gene testing in the study population. ResultsThe overall proportion of CT recommendations was reduced from 24.6% to 15.2% after 21-gene testing, with a major impact in patients initially considered for CT plus hormone therapy (CHT). In these patients, the total budget was reduced, leading to a net saving of -€81,017. The greater the physician propensity to prescribe CHT, the higher the potential savings for the health system from sparing CT in most tested patients. ConclusionsOur real-life experience suggests that all intermediate-risk ER+/HER2-eBC patients who are initially deemed candidates for CHT should be tested with the 21-gene test. The potential to spare CT in at least half of them offers relevant advantages for patients and national health services.

Abstract P3-08-47: Prediction of the high-risk oncotype Dx recurrence score from clinicopathologic factors: A report from a cancer reference center in Brazil

Abstract Background: Oncotype DX Recurrence Score (ODXRS) is a 21-gene test that has been validated as an assay to effectively predict recurrence and chemotherapy benefit for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) and lymph node negative (pN0) breast cancer. It has also been used in patients with 1-3 positive lymph nodes (pN1) in clinical practice. Methods: A single-institution retrospective study was conducted to include all patients who had an ODXRS test in our cancer center from 2005 to 2019. Clinical and pathology data were extracted from electronic charts. The predicted ODXRS was recorded and correlated with selected clinicopathological characteristics potentially related to a high-risk profile. A multivariate logistic regression model was performed to identify independent predictors of high-risk ODXRS (≥26) and ROC analysis was done to provide performance of the final model, found through exhaustive screening using Information Criteria (AIC). Associations with p<0.05 were considered to be statistically significant. Results: Two hundred and seventy-five patients with estrogen receptor positive, HER2 negative, pN0 or pN1 breast cancer were included. Median age was 55 years (range, 29 - 79). The ODXRS was low (<11), intermediate (11-25) and high (>25) in 58 (21.1%), 178 (64.7%) and 39 (14.2%) patients, respectively. On univariate and multivariate analyses, progesterone receptor negative status (p<0.001 for both), high histological grade (p<0.001 for both) and KI-67 proliferation rate (p<0.001 and p=0.002, respectively) were statistically significantly associated with high-risk ODXRS. In our prediction model, high-risk ODXRS could be predicted with a sensitivity of 67%, specificity of 83%, and an area under the curve of 0.82. Age, multifocal disease, tumor histological type, T-stage, N-stage, lymphovascular invasion and body mass index were not associated with ODXRS (Table 1). Conclusions: In our study, a prediction model based on progesterone receptor status, histological grade and KI-67 proliferation rate can be used to predict high-risk ODXRS. In resource-constrained healthcare systems, such model might help identify high-risk patients who would benefit from adjuvant chemotherapy without incurring the costs of the ODXRS test. Multivariable logistic regression Models for predicting High-Risk (>25) scores.Clinical and pathological variablesUnivariate OR (95%CI) pMultivariate OR (95%CI) pPatient age ≤ 50> 501.16 (0.58-2.36)0.682Multifocal tumorAbsent Present1.78 (0.81-3.70)0.1332.38 (0.86-6.34)0.085HistologyDuctalLobular1.14 (0.43 – 2.69)0.778Other0.65 (0.18 – 1.79)0.447T staging T1T2/31.25 (0.53-2.72)0.595N stagingN0N1 0.62 (0.20-1.55)0.347High-grade histologyG1/2G310.44 (3.97-28.25)<0.00110.51 (3.11-36.68)<0.001Lymphovascular invasionAbsentPresent1.18 (0.51-2.55)0.6881.15 (0.43 – 2.88)0.765PR positiveNegativePositive0.18 (0.07-0.47)<0.0010.10 (0.03-0.32)<0.001Ki-67, mean (±SD)1.06 (1.03-1.09)<0.0011.06 (1.02-1.09)0.002BMI (Kg/m2), mean (±SD)0.97 (0.88-1.05)0.479 Citation Format: Leandro JonataCarvalho Oliveira, Thais BacciliCury Megid, Marina Sahade, Andrea Kazumi Shimada, Daniele Xavier Assad, Joao Vicente Horvat, Antonildes Nascimento Assunção, Artur Katz, Max Senna Mano. Prediction of the high-risk oncotype Dx recurrence score from clinicopathologic factors: A report from a cancer reference center in Brazil [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-47.

Associations between clinical-pathological parameters and biomarkers, HER-2, TYMS, RRMI, and 21-gene recurrence score in breast cancer

BackgroundChemotherapy is the predominant treatment option for patients with breast cancer. Selection of patients according to biomarker will improve chemotherapy efficacy. In the present study, we examined the relations of the expression of candidate genes and 21-recurrence score (RS) results to patients’ demographic characteristics, histopathological factors, and outcomes. MethodsA total of 146 patients were enrolled in this study. The patients underwent 21-gene RS testing. In addition, expressions of candidate genes, TYMS, RRM1, TUBB3, TOP2A, PTEN, were detected. Information was obtained on age, tumor size, TMN stage, tumor grade, and status of Ki-67, HER2, ER and PR. The treatment information on the type of endocrine therapy was also obtained. ResultsResults clearly showed that the 21-gene RS significantly correlated with the TNM stage of breast cancer (P = 0.047). The RS also correlated with the number of sentinel lymph node (P = 0.038). The pathological type of tumors was strongly associated with the expression of RRM1 (P < 0.015), and slightly correlated with TYMS (P = 0.095) and tumor size (P = 0.061). Further analysis showed that TYMS and RRM1 were two independent factors affecting the disease progression of patients. Besides, for HER-2 stain, staining of grade 2 or above significantly increased the risk of disease progression. ConclusionOur studies showed that TNM stage and sentinel lymph node were important clinical parameters correlated with 21-gene RS results. Also, RRM1, TYMS and HER2 expressions were independent factors associated with disease progression in breast cancer patients. Future study is warranted to investigate the usefulness of these genes in treatment efficacy.

21-Gene recurrence score influences the chemotherapy decision for patients with breast cancer of different luminal subtypes.

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR+/HER2- patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58-152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90-6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42-145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39-1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR+/HER2- patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation.

Clinical relevance of 21-gene recurrence score with lymph node involvement in HR+HER2- early breast cancer: A tumor size-match paired cohort study.

e12059 Background: Axillary lymph node (LN) involvement is significantly related with high recurrent risk and influenced by tumor size, histologic grade and subtype in early breast cancer. For hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer without LN involvement, 21-gene recurrence score (RS) provides an effective method evaluating the risk of recurrence and metastasis. But the correlation between RS and LN involvement is not clear currently. To investigate the effect of RS on LN involvement, we designed a retrospective cohort study based on the data of tumor size-match LN+/- HR+HER2- breast cancer. Methods: The luminal type (ER+, PR+ and HER2-) early breast cancer (cT1-2) patients with 1~3 LN+ were enrolled and were tumor size-match paired (1:3) with those LN- during the same period. We compared the 21-gene RS between the LN+ and LN- group by univariate and multivariate analyses. Results: From April 2016 to May 2018, there were 65 LN+ cases undergoing 21-gene test included and 195 LN- cases were paired. With tumor size matched, the LN+ group had significantly younger age, more positive family history, higher histologic grade and higher RS than LN- group. All those factors, excepted histologic grade, were further confirmed in multivariate analysis (Table). Conclusions: After adjusted by tumor size, RS may have a significantly independent correlation with LN involvement in HR+HER2- early breast cancer. Total HR+HER2- cases’ tumor size-match paired (1:3) clinic pathologic and RS data. Clinical trial information: NCT03638648. [Table: see text]

Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2− early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2–47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.

Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study

PurposeThe Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole.MethodsNEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors ≥ 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS < 18 versus RS ≥ 31. Secondary endpoints included evaluation of clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result, ESR1 and PGR single-gene scores, and ER gene-group score.ResultsOf 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS < 18, 28.5% had RS18–30, and 18.3% had RS ≥ 31. Clinical response rates were 54% (RS < 18), 42% (RS18–30), and 22% (RS ≥ 31). A higher proportion of patients with RS < 18 had clinical responses (p < 0.001 vs. RS ≥ 31). In multivariable analyses, continuous Recurrence Score result (p < 0.001), ESR1 score (p = 0.049), PGR score (p < 0.001), and ER gene-group score (p < 0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS < 18 vs. RS ≥ 31, p = 0.010).ConclusionThe Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.

First person: George Sledge, Jr, MD: Former ASCO president leads breast cancer research and mentors Stanford faculty.

First person: George Sledge, Jr, MD: Former ASCO president leads breast cancer research and mentors Stanford faculty.

Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy: Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy.

Many Women With the Most Common Form of Breast Cancer Can Skip Chemotherapy: Study finds that approximately 70% of patients with this form of the disease do not need adjuvant chemotherapy.

Abstract 2971: Digital image analysis based IHC4+C assay and prognosis in hormone receptor-positive breast cancer

Abstract Background The immunohistochemical (IHC) 4 + clinical treatment score (C) i.e. IHC4+C assay combines IHC assessment of four routinely measured markers in the clinical setting, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and KI67, with other clinical parameters for aiding decision-making on adjuvant chemotherapy in hormone positive (HR+) breast cancer. It is low cost, widely available and has been shown to provide similar prognostic information to the 21-gene (Oncotype DX) test. Clinical use of IHC4+C is limited by the need for standardized scoring of the IHC markers. Here, we examine the prognostic value of a digital image analysis (DIA) based IHC4+C assay in two study populations and compare this with pathologists' visual assay in a subset of patients. We also evaluated its potential clinical relevance in relation to the Nottingham prognostic index [NPI; i.e. low (&amp;lt;3.4), intermediate (3.4-5.4) and high (&amp;gt;5.4)] and IHC defined breast cancer subtypes (i.e. luminal A-like and B-like). Methods Using DIA data on ER, PR, HER2 and KI67, in addition to clinicopathological characteristics of tumors, we computed DIA based IHC4+C (i.e. DIAIHC4+C) assay for 2,034 women from study populations in Poland (PBCS) and the United Kingdom (SEARCH). A total of 246 deaths occurred over a median follow-up period of 6.7 years. A relevant threshold was determined using quartile analysis and the relationship between dichotomous categories (&amp;gt;75th vs ≤ 75th percentile) of DIAIHC4+C and 10-year breast cancer specific survival (BCSS) was investigated using Kaplan-Meier survival curves and in Cox proportional hazard regression models, overall and stratified by study, NPI and subtype. Results DIAIHC4+C score was associated with worse 10-year BCSS overall [HR (95% CI) &amp;gt;75th vs ≤ 75th percentile = 2.92 (1.77, 4.82); p-value &amp;lt;0.0001] and in both the PBCS [3.48 (1.40, 8.65); p-value = 0.007] and SEARCH [3.87 (2.24, 6.68); p-value &amp;lt;0.0001] study populations. DIAIHC4+C was associated with significantly worse survival outcomes in women with intermediate NPI [1.94 (1.31, 2.88); p-value = 0.001] and luminal A-like subtype of HR+ tumors [5.37 (3.50, 8.26); p-value &amp;lt;0.0001]. DIA and visual IHC4+C results were highly correlated (r = 0.95) and survival associations and model fit parameters were similar for DIA [3.82 (2.08, 7.00); p-value &amp;lt; 0.0001; AIC = 472.3] and visual [4.73 (2.55, 8.76); p-value &amp;lt; 0.0001; AIC = 466.1] IHC4+C scores amongst 444 patients with data from both sources. Conclusion These findings are in support of the prognostic value of DIAIHC4+C assay in HR+ breast cancer and demonstrate its potential clinical relevance as an adjunct to the NPI. Given the advantages of being high-throughput and highly reproducible, DIA based methods could find use in the standardization of the analytical processes for the IHC4+C assay. Citation Format: Mustapha Abubakar, Paul D. Pharoah, Mark E. Sherman, Montserrat Garcia-Closas, Mitch Dowsett. Digital image analysis based IHC4+C assay and prognosis in hormone receptor-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2971.

Abstract PD7-13: Molecular characterization and mortality from breast cancer in men

Abstract Background: Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Methods: We studied men and women with hormone receptor (HR)-positive breast cancer and 21-gene test (RS) results. Patients with negative nodes, micrometastasis, and 1-3 positive nodes were included. Differences in clinical characteristics and gene expression were determined and distribution of RS results was analyzed and correlated with 5-year breast cancer specific survival (BCSS) and overall survival (OS). Results: There were 3806 men and 571115 women. Men were older than women (mean age 64.2 vs. 59.1 years, p&amp;lt;0.001). RS &amp;lt;18 predominated in both genders, but RS ≥31 was more frequent in men (12.4% vs. 7.4%, p&amp;lt;0.001) as were very low scores (RS &amp;lt;11) (33.8% vs. 22.1%, p&amp;lt;0.001). Mean gene expression was higher in men for the ER, proliferation, and invasion groups. ER was lowest and PR highest in women &amp;lt;50 years, with a progressive increase in ER with age. Men &amp;lt;50 years had slightly lower ER and PR compared to older men. Survival data was available from SEER for 322 men and 55842 women. 5-year estimates for BCSS differed significantly between RS groups for both men (p=0.003) and women (p&amp;lt;0.001). For men, the 5-year BCSS was 99.0% and 95.9% with RS &amp;lt;18 and RS 18-30, respectively, and for women it was 99.5% and 98.6%, regardless of nodal status. RS ≥31 was associated with a 5-year BCSS of 81.0% in men and 94.9% in women. The prognostic utility of RS was evident in both men and women, despite the progressive increase in adjuvant chemotherapy use with higher RS results. 5-year BCSS and OS were overall lower in men than in women. Conclusion: This large genomic study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for 21-gene testing in both men and women, regardless of nodal status. Future adjuvant trials in ER-positive breast cancer should focus on targeting endocrine-resistance in those patients with RS ≥31, and need to consider the weight of competing causes of mortality when investigating the value of any additional treatment beyond endocrine therapy. Citation Format: Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S. Molecular characterization and mortality from breast cancer in men [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-13.

Population-Based Study to Determine the Health System Costs of Using the 21-Gene Assay.

Purpose The 21-gene assay Oncotype Dx (Genomic Health, Redwood City, CA) test is used to aid the decision about chemotherapy in patients with hormone receptor-positive breast cancer who received endocrine therapy. Economic studies to support test adoption used decision-analytic models with assumptions and data derived from disparate sources. The objective was to evaluate whether the 21-gene assay test resulted in an overall cost expense or saving to the health system. Patients and Methods One thousand participants enrolled in a field evaluation study, were linked to population-level health system administrative databases, and were observed for 20 months. The cost for the cohort, which included the cost of the test, subsequent treatments received, and health care encounters, was determined. The cost in the absence of the test was compared with the pretest recommendation about chemotherapy from the field study for a base case and under scenarios that reflected different adjuvant chemotherapy use. Overall health system costs and incremental costs were calculated. Results The 21-gene assay resulted in a net decrease in chemotherapy use of 23%. For the base case incremental analysis, the actual overall health system cost of this cohort, including the cost of 21-gene assay, was $29.2 million compared with $26.2 million in the absence of the test-an increase of $3.1 million. For three of the four scenario analyses, the actual overall cost to the health system exceeded the estimated cost in the absence of the test. Results showed that, when at least half of the population received adjuvant chemotherapy, the cost increased to $30.2 million. Conclusion The use of real-world administrative data showed that, despite lower rates of chemotherapy use, the 21-gene assay test results in an overall incremental cost to the health care system in the short-term under most assumptions.

Clinical Impact of 21-Gene Recurrence Score Test Within the Veterans Health Administration: Utilization and Receipt of Guideline-Concordant Care

IntroductionEnsuring guideline-concordant cancer care is a Department of Veterans Affairs (VA) priority, especially as the number of breast cancer patients at VA medical centers (VAMCs) grows. We assessed the utilization and clinical impact of the 21-gene Recurrence Score test, which predicts 10-year risk of breast cancer recurrence and the likelihood of chemotherapy benefit, on veterans newly diagnosed with breast cancer. Patients and MethodsWe conducted a retrospective cohort study using 2011-2012 VA Central Cancer Registry, chart review, and laboratory test data. Independent variables assessed included patient and site-of-care characteristics. The outcome of interest was whether newly diagnosed, eligible (node negative, hormone-receptor positive, human epidermal growth factor receptor 2 [HER2] negative) veterans underwent the 21-gene test. We performed descriptive statistics on all patients and multivariate logistic regression to determine associations. We correlated treatments received with test results. ResultsAmong 328 eligible veterans, 82 (25%) had the 21-gene test; 100 eligible veterans (30%) sought care at a VAMC where no tests were ordered. Receiving care at a VAMC that had women's health services (odds ratio [OR], 1.84, 95% confidence interval [CI], 1.05-3.22) and having tumor characteristics meeting the National Comprehensive Cancer Network 2010 test criteria (OR, 3.06, 95% CI, 1.69-5.57) were positive predictors of testing; increasing age (OR, 0.93, 95% CI, 0.91-0.96 per year) and fee-based care (OR, 0.46, 95% CI, 0.26-0.82) were negative predictors. The majority of tested patients received guideline-concordant care. ConclusionSite of care and tumor characteristics were important predictors of test uptake. Facilitating delivery of guideline-concordant cancer care requires improved laboratory informatics and clinical decision support.

21-Gene recurrence score testing among Medicare beneficiaries with breast cancer in 2010-2013.

We evaluated national patient-level utilization of the 21-gene recurrence score (21-gene RS) test among Medicare beneficiaries with breast cancer. We analyzed clinical, demographic, and regional factors that predict testing. Using 2010-2013 Medicare claims, we conducted a retrospective study of breast cancer patients. The outcome variable was whether the patient underwent testing. Independent variables expected to predict testing were age, gender, race, Medicaid status, clinical characteristics, and hospital referral region (HRR). From 2010 to 2013, the number of test orders increased by 23.0%. Of the 256,818 patients identified in 2011-2012 claims, 25,352 (9.9%) underwent the 21-gene RS test. Estrogen receptor-positive status was the strongest positive predictor of testing (odds ratio (OR) 2.58, 95% confidence interval (CI) 2.48-2.69). White patients were more likely to be tested than minorities (OR 1.46, 95% CI 1.39-1.52). Secondary cancer was the strongest negative predictor. Medicaid recipients were less likely to be tested (OR 0.74, 95% CI 0.71-0.78). The likelihood of testing decreased with increasing age and comorbidities. Despite widespread implementation of the 21-gene RS test, minorities and Medicaid recipients had less access to testing. Many patients with serious comorbidities or advanced age were tested even though the risk algorithm may not have been applicable to them.Genet Med advance online publication 23 March 2017.

Abstract P6-07-28: The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study

Abstract BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in breast cancer (BC). The 21-gene assay test is used to estimate the risk of recurrence and to predict the benefit of adjuvant chemotherapy (ACT) at an early stage of hormone-receptor-positive (ER+) BC. This study aims to examine the implications of RecurrenceScore (RS) testing within the routine clinical practices in France. METHODS: We conducted a prospective multicentert study, with voluntary participation, involving women with ER+, HER2-, BC. Performing the assay was left at the discretionof the physicians. The final treatment decision was discussed pre and post assay among tumor board (TB). The therapeutic changes after knowledge of RS were collected. RS and classical BC prognostic markers were investigated in parallel including an estimate of the budget impact of the assay. RESULTS: 603 patients were included in this analysis (tumor size ≤ 20 mm: 70.6%; node-negative patients: 61.2%; SBR 2: 74.9%). After the first TB, ACT was recommended for 529 patients (88.0%) and hormonotherapy (HT) alone for 74 patients (12.0%). The RS was low for 59.7% of the cases, intermediate for 34.0% and high for 6.3%. Based on RS results, second TB changed treatment decision for 70.48% of patients, avoiding CT in 64 % of cases. Only 24% received ACT while 76% received HT alone. The calculated budget impact as a minimal estimate according to the French healthcare payer perspective is estimated at a savings of € 570 per patient, corresponding to a global cost-saving of € 221,730. CONCLUSION: The results of this “real life” study confirm that the 21-gene assay had a significant impact on therapeutic decision. These findings warrant further consideration for the use of this genomic assay in patients with early stage BC in France. Citation Format: Gligorov J, Dohollou N, Mouysset JL, Laplaige P, Fignon A, Lafuma A, Michaud P. The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-28.

Dissemination of 21-gene assay testing among female breast cancer patients in the US.

6553Background: The 21-gene assay has been used in clinical practice since 2004 to predict the recurrence and chemotherapy benefit of breast cancer in patients with hormone receptor positive (HR+) ...

Utilization of the 21-gene RS test among Medicare beneficiaries with breast cancer in 2011.

e18078Background: The numbers of genomic tests and indications for testing are rapidly expanding. By identifying patients’ response to treatment, genomic risk stratification tools can improve healt...

Abstract ES8-2: Prognostic indicators in treatment of DCIS

Abstract The goal of DCIS treatment is to avoid a future invasive breast cancer. Invasive breast cancer risk is heterogeneous across the population of DCIS patients. More than 40% of women with minimal, low grade DCIS will develop invasive breast cancer if left untreated and followed for more than 10 years. Risk of invasive recurrence is about 2% per year for DCIS treated by simple excision (lower for small low grade lesions and higher for larger high grade lesions). A reliable approach for risk-stratifying individual DCIS lesions could permit tailored approaches to therapy or avoidance of therapy all together in the lowest risk women. Screen-detected, grade 1 and 2 micropapillary DCIS in older women is likely the lowest risk lesion. Progression to invasive breast cancer is more likely related to focal myoepithelial cell dysfunction than molecular alterations in the bulk luminal cell populations. Nevertheless, p16, ER, COX2, HER-2/neu, and Ki67 staining patterns in the bulk luminal cell population have been linked to recurrence risk. A 12 gene recurrence score has been shown to predict the risk of recurrence for DCIS treated by excision without radiation. This assay was adapted from the 21-gene OncoTypeDx test and is weighted heavily towards proliferation markers. Accurate prediction of invasive recurrence risk will likely require detection of focal alterations in myopeithelial cells and the basement membrane. Citation Format: Euhus DM. Prognostic indicators in treatment of DCIS. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES8-2.

Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland

The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node-negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing. Between October 2011 and February 2013, a national, retrospective, cross-sectional observational study of ER+, N0 BC pts tested with the 21-gene test was conducted. Surveyed breast medical oncologists, provided the assumption for the decision impact analysis that grade (G) 1 pts would not have received CT before testing and G2/3 pts would have received CT before testing. Descriptive statistical analyses were performed. 592 pts were identified; Low, intermediate and high recurrence score were identified in 53, 36 and 10 % pts, respectively. 384 (70 %) pts had G2, 129 (22 %) G3 and 76 (13 %) G1 tumours. Post testing, 345 pts (59 %) experienced a change in CT decision; 339 changed to hormone therapy alone and 6 advised to receive CT. 172 (30 %) pts received CT, 12 (3.9 %) of pts with low scores, 108 (50.9 %) of intermediate risk and 50 (90.9 %) of pts with high risk scores. Net reduction in CT use was 58 % and net savings achieved were €793,565. Since public reimbursement, the introduction of the 21-gene test has resulted in a significant reduction in chemotherapy administration and cost savings for the Irish public healthcare system.