21-gene Recurrence Score Testing Research Articles

Abstract OT3-04-03: The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland

Abstract BACKGROUND For Estrogen Receptor (ER) positive, early stage breast cancer, the 21 gene Recurrence Score (RS) has clinical use both as a prognostic tool and to predict chemotherapy benefit. The availability of this tool in Ireland has led to a reduction in the use of adjuvant chemotherapy for women with lymph node (LN) negative disease. However, the RS is not routinely funded for patients with LN positive (LN+) breast cancer in Ireland. In addition, there are limited international data on the use of this tool in the preoperative setting. In this prospective observational study, we are investigating whether access to the 21 gene RS leads to a reduction in the receipt of chemotherapy for patients with ER+, LN+ breast cancer, and to correlate the 21 gene RS with response to preoperative systemic therapy. TRIAL DESIGN This is a national, multi-site, prospective, observational study that will examine the impact of the 21 gene RS on chemotherapy recommendations in both the neoadjuvant and adjuvant setting. Prior to and following tumor testing with the 21 gene RS, Physicians will complete a questionnaire which details type and strength of systemic therapy recommendations. ELIGIBILITY Cohort 1 (postoperative) will include patients with ER+ tumors of any size with involvement of 1-3 lymph nodes (N1 including micrometastases). Cohort 2 (preoperative) will include patients with ER+, T2-T4 tumors with biopsy proven nodal metastases. Both cohorts will have ECOG PS 0 or 1 and be fit for consideration of chemotherapy as determined by the Investigator. SPECIFIC AIMS The primary endpoint is the percentage reduction in the number of patients for whom treating physicians recommend chemotherapy after testing with 21 gene RS. Secondary endpoints include the correlation between the 21 gene RS and residual cancer burden score, as well as pathological, clinical and radiological response rates. The economic impact of the 21 gene RS in ER+, LN+ will also be assessed. STATISTICAL METHODS The sample size is based on similar decision impact studies conducted in other countries. Physician recommendations for chemotherapy pre 21-gene RS and recommendations post 21-gene RS testing will be compared and percentage change estimated with 95% confidence intervals. For secondary endpoints, the Pearson correlation coefficient (rho) will be used to examine the strength of the correlation between the 21 gene RS category and response. A budget impact model will be used to estimate the cost reduction in adjuvant chemotherapy as a result of 21-gene RS testing. PRESENT ACCRUAL AND TARGET ACCRUAL Target accrual is 75 in each of the neoadjuvant and adjuvant cohorts to total 150 patients. Supported by Genomic Health. Citation Format: Keegan NM, Milewski M, Kelly CM, Murphy V, Chao C, Walsh J, Kennedy MJ, O'Connor M, Murphy C, O'Reilly S, Keane M, Duffy K, Hennessy B, Morris PG. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland [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 OT3-04-03.

Abstract P5-08-07: Appropriate use of the 21-gene recurrence score (RS) assay across Michigan

Abstract Background: The 21-gene RS assay is used to assess prognosis and to predict response to adjuvant chemotherapy in patients with early stage hormone receptor positive, Her2 negative invasive breast cancer. The National Comprehensive Cancer Network (NCCN) first recommended consideration of testing of appropriate patients with the RS assay in 2008. We examined trends in the use of testing with the RS assay in hospitals across Michigan from 2006 through 2013 using data from the Michigan Breast Oncology Quality Initiative (MiBOQI), a Blue Cross Blue Shield of Michigan/Blue Care Network-sponsored quality initiative. Methods: Demographic, pathologic, and treatment data for women with breast cancer treated at all 25 hospitals participating in MiBOQI were abstracted from the medical record. Patients were excluded if they had stage 0 or IV disease at diagnosis, received neoadjuvant therapy, had bilateral breast cancer, or had a prior history of breast cancer. The primary outcome was the percentage of patients eligible for testing according to NCCN criteria (version 2010) who underwent testing with the RS assay. Analyses were performed using the statistical software R, Version 3.0.1. Results: Of the 18,046 patients in the MiBOQI Registry from 2006-2013 who met inclusion and exclusion criteria, 7133 (39.5%) met the NCCN criteria for testing (eligible). The rate of testing increased from 2006 to 2013 in both the eligible and ineligible cohorts, and varied by site. 21-Gene Recurrence Score (RS) Testing in MiBOQI, 2006-2013FactorEligible (n=7133)Ineligible (n=10913)Tested with RS assay3920 (55.5%)1424 (13.0%)Testing rate in 200643.8%7.3%Testing rate in 201362.3%19.6%Testing by site, 2006-2013 (range)35.8% - 73.3%6.8% - 26.2% Testing of the eligible cohort was statistically significantly associated with younger age, lower tumor grade, and lack of nodal involvement. Overall, 73.4% of patients whose tumors were tested with the RS assay met the NCCN criteria for testing and were deemed appropriately tested. This rate of appropriate testing ranged from 60.8% to 85.4% across sites. Of all patients who underwent testing, 498 (9.3%) had 1 or more positive lymph nodes (>0.2 cm). Receipt of chemotherapy was lower in eligible patients who were tested compared to those not tested (25.5% vs 29.9%, p<0.001). Of the 2387 eligible patients with RS < 18, 117 (5.5%) received chemotherapy, which ranged from 0% - 13.6% across the 25 sites. Of the 341 patients with RS > 30, 56 (9.8%) did not receive treatment with chemotherapy, which ranged from 0% - 50% across the sites. Of the 1192 patients with RS 18-30, 502 (45.7%) received chemotherapy, ranging from 14.5% for RS 18 to 72.5% for RS 30. Conclusions: In sites across Michigan the majority of patients whose tumors were tested with the RS assay were in accordance with the NCCN guidelines, although there was considerable variability across sites. The rate of testing for patients who do not meet the NCCN criteria is increasing. There is very low inappropriate use of the recurrence score for making chemotherapy treatment decisions. Citation Format: Ali HY, Munir K, Braun T, Griggs JJ, Silver SM, Gorski DH, Breslin TM, Henry NL. Appropriate use of the 21-gene recurrence score (RS) assay across Michigan. [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 P5-08-07.

Implementation of the 21-gene recurrence score test in the United States in 2011.

We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing. Genomic Health provided test orders for calendar year 2011.We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital's institutional and regional characteristics. In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96-4.70), advanced imaging (OR, 2.19; CI, 1.78-2.68), high-complexity laboratory (OR, 2.15; CI, 1.24-3.70), affiliation with a medical school (OR, 1.57; CI, 1.31-1.88), and reconstructive surgery (OR, 1.23; CI, 1.01-1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83-5.03), above-mean income (OR, 1.37; CI, 1.11-1.69), and education (OR, 1.26; CI, 1.03-1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07-0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997-0.999), with a 15% decrease in likelihood for every 100 miles. Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states.Genet Med 18 10, 982-990.

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.

P253 Economic impact of 21-gene recurrence score testing on early stage breast cancer in Ireland

P253 Economic impact of 21-gene recurrence score testing on early stage breast cancer in Ireland

21-gene Recurrence Score testing and subsequent treatment decisions in patients (pts) with estrogen-receptor-positive (ER+) early-stage breast cancer (ESBC).

30 Background: The utilization of the 21-gene Recurrence Score (Oncotype DX) in community settings is now well established for ER+, node negative (N-) pts with ESBC. The utility of the Recurrence Score result is to guide treatment decisions and spare exposure to chemotherapy (CT) in pts that have little likelihood of benefitting. To better understand physician behavior as it relates to OncotypeDX testing, we examined the characteristics of pts tested versus not tested, the Recurrence Score distribution and treatment patterns in approximately 160 pts with ESBC seen in 2010. In addition, provider utilization and treatment patterns were also assessed. Methods: Using data from 2010, the number of pts who were eligible to undergo OncotypeDX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, ER+, HER2-negative ESBC. We determined the number of pts with a Recurrence Score value in the low (RS <18), intermediate (int; RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of the 233 pts identified with ESBC, 158 were eligible for OncotypeDX testing and 107 (67.7%) underwent testing. Fifty-five percent of pts were low, 37% int, and 7.7% high-risk, respectively. Nineteen percent of low, 56% of int, and 100% of high-risk pts received CT. In the 11 pts with a low Recurrence Score result that received CT, the reason cited was pt decision in 4 and young age in 3. Conclusions: Oncotype DX use in the community is well established. Recurrence Score-guided use of CT in the low- and int-risk groups was as expected based on adjuvant chemotherapy guidelines; however, there were still some physicians treating low Recurrence Score pts with CT-mostly based on younger age or larger tumors. Data from 2011 and 2012 will be included in the final presentation allowing greater insight into pt groups less represented in the single year experience.

Decline in the Use of Anthracyclines for Breast Cancer

To determine the patterns of use of anthracycline- and taxane-based chemotherapy for breast cancer treatment. Claims from a 5% national Medicare sample and from a nationally representative claims database (Marketscan) from 1998 to 2009 were used. Patients with International Classification of Diseases (ICD), ninth revision, codes indicating breast cancer, ICD and Common Procedural Terminology codes indicating breast surgery, and claims for chemotherapy between 3 months before and 12 months after surgery comprised the study cohort. Chemotherapy was classified as anthracycline-based or taxane-based, and the percentages of use were calculated. Piecewise regression models were used to identify the inflection points in the rates of chemotherapy use. The effect of patient characteristics on receiving different types of chemotherapy was estimated by multivariable logistic regression models. A total of 4,458 patients were included in the Medicare cohort and 30,422 in the private insurance cohort. After 2005, a sharp increase in the use of taxane-based chemotherapy and a decline in anthracycline-based chemotherapy was seen. By 2008 in the Medicare cohort, 51% of patients received taxane-based and 32% received anthracycline-based chemotherapy. By the end of 2008, the majority of patients younger than 65 years were also receiving taxane-based chemotherapy. Patients younger than 35 years were less likely to be treated with a taxane-based regimen, whereas patients who underwent 21-gene recurrence score testing and those treated with trastuzumab were more likely to receive taxane-based chemotherapy. The use of anthracycline-based chemotherapy has declined, and the majority of patients with breast cancer are instead receiving taxane-based chemotherapy. The potential impact on patient outcomes is unknown.

21‐Gene recurrence scores

African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role.