Oncotype DX Assay Research Articles

How Canadian Oncologists Use Oncotype DX for Treatment of Breast Cancer Patients.

Background: The literature suggests that medical oncologists differ on how they use the Oncotype DX (ODX) genomic assay for making decisions about systemic therapy in breast cancer patients. Given the emergence of data supporting the use of genomic profiling for the prognosis and predicting benefit of chemotherapy, we surveyed medical oncologists in Canada to assess their usage and perception of the ODX assay. Methods: A 34-item survey was distributed to Canadian medical oncologists via the Canadian Association of Medical Oncologists. Data was collected on physician demographics, ODX usage patterns, and physicians’ perception of the impact clinical and pathologic characteristics make on ODX utilization. Results: Response rate was 20.6% with 47 responses received from 228 survey sent. Forty-five responses were eligible for analysis. Sixty-two percent (28/45) of respondents treated predominantly breast cancer, and 60% (27/45) have been in practice for at least 10 years. The most cited reason for using ODX was to avoid giving patients unnecessary chemotherapy (64%; 29/45). Sixty-seven percent (30/45) deferred making treatment decisions until ODX testing was completed. Factors most strongly impacting ODX utilization included: patient request, medical comorbidities and tumor grade. In clinical scenarios, ODX was more frequently selected for patients aged 40–65 (vs. <40 or >65), grade 2 tumors (vs. grade 1 or 3), and Ki-67 index of 10–20% (vs. <10% or >20%). Conclusions: This survey demonstrated that Canadian medical oncologists are preferentially using ODX to avoid giving patients unnecessary chemotherapy. The utilization of ODX is mainly in patients with intermediate clinical and pathologic features.

Association between Oncotype DX recurrence score and dynamic contrast-enhanced MRI features in patients with estrogen receptor-positive HER2-negative invasive breast cancer

BackgroundOncotype DX is a multigene assay used in breast cancer, and the result provided as a ‘recurrence score (RS)’ corresponds to the risk of a cancer recurrence and the chemotherapeutic benefit in estrogen receptor (ER)-positive human epidermal growth factor receptor (HER)2-negative invasive breast cancer. However, its accessibility is limited. PurposeTo evaluate whether magnetic resonance imaging (MRI) could be used to predict Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer. Material and methodsWe enrolled 473 patients with ER-positive HER2-negative invasive breast cancer who underwent a preoperative MRI and Oncotype DX assay between January 2015 and December 2018. The MRI was reviewed and associations between Oncotype DX RS values were evaluated. Logistic regression analysis was used to identify independent predictors of high and low RS. ResultsOf the 485 cancers, 288 (59.4%) had low (<18), 155 (31.9%) had intermediate (18–30), and 42 (8.7%) had high (≥31) RS. Multiple logistic regression analysis revealed that a round shape (odds ratio [OR] = 2.554, P = 0.089) and low proportion of washout component (OR = 1.011, P = 0.014) were associated with low RS and that heterogeneously dense (OR = 3.205, P = 0.007) or scattered fibroglandular (OR = 3.776, P = 0.005) breast tissue, a non-spiculated margin (OR = 5.435, P = 0.007), and low proportion of persistent component (OR = 1.012, P = 0.036) were associated with high RS. ConclusionMRI features showed the potential for the discrimination of Oncotype DX RS in patients with ER-positive HER2-negative invasive breast cancer.

Automated immunohistochemical assessment ability to evaluate estrogen and progesterone receptor status compared with quantitative reverse transcription-polymerase chain reaction in breast carcinoma patients.

BackgroundThis study aimed to investigate the capability of an automated immunohistochemical (IHC) evaluation of hormonal receptor status in breast cancer patients compared to a well-validated quantitative reverse transcription–polymerase chain reaction (RT-qPCR) method.MethodsThis study included 93 invasive breast carcinoma cases that had both standard IHC assay and Oncotype Dx assay results. The same paraffin blocks on which Oncotype Dx assay had been performed were selected. Estrogen receptor (ER) and progesterone receptor (PR) receptor status were evaluated through IHC stains using SP1 monoclonal antibody for ER, and 1E2 monoclonal antibody for PR. All ER and PR immunostained slides were scanned, and invasive tumor areas were marked. Using the Quant-Center image analyzer provided by 3DHISTECH, IHC staining of hormone receptors was measured and converted to histochemical scores (H scores). Pearson correlation coefficients were calculated between Oncotype Dx hormone receptor scores and H scores, and between Oncotype Dx scores and Allred scores.ResultsH scores measured by an automated imaging system showed high concordance with RT-qPCR scores. ER concordance was 98.9% (92/93), and PR concordance was 91.4% (85/93). The correlation magnitude between automated H scores and RT-qPCR scores was high and comparable to those of Allred scores (for ER, 0.51 vs. 0.37 [p = .121], for PR, 0.70 vs. 0.72 [p = .39]).ConclusionsAutomated H scores showed a high concordance with quantitative mRNA expression levels measured by RT-qPCR.

Propensity score analysis of the prognostic value of genomic assays for breast cancer in diverse populations using the National Cancer Data Base.

Genomic assays such as Oncotype Dx (ODX) and MammaPrint are used for risk-adapted treatment decisions among patients with early breast cancer. However, to the authors' knowledge, concordance between genomic assays is modest. Using real-world data, the authors performed a comparative analysis of ODX and MammaPrint. A cohort of women diagnosed with early-stage, hormone receptor-positive breast cancer who received ODX or MammaPrint was established using the National Cancer Data Base (NCDB) for 2010 through 2016. Using the propensity score matching method, 2 groups of patients with similar clinical and demographic characteristics were defined: one group received ODX and the other received MammaPrint. The authors examined the association between use of the ODX or MammaPrint assays and overall survival using Cox models. Of the 451,693 eligible patients, approximately 45.3% received ODX and 1.8% received MammaPrint testing. The use of ODX increased from 36.1% in 2010 to 49.9% in 2016, whereas use of MammaPrint increased from 0.5% in 2010 to 3.3% in 2016. The authors matched 5042 patients who received ODX with 5042 patients who received MammaPrint. The 5-year risks of death for the MammaPrint low-risk group and the ODX low-risk group were 3.4% and 4.7%, respectively. The prognostic value of MammaPrint was similar to that of ODX; the C-index was 0.614 (95% confidence interval, 0.572-0.657) for MammaPrint and 0.581 (95% confidence interval, 0.530-0.631) for ODX. There was a difference in the performance of the ODX assay observed across racial and/or ethnic groups (P<.001), with a slightly better performance noted among white compared with African American and Hispanic individuals. Both the ODX and MammaPrint tests are good at identifying low-risk individuals who could be spared chemotherapy. The suboptimal performance of ODX in ethnic minority individuals deserves further investigation.

Gene Expression Assay in the Management of Early Breast Cancer.

The addition of adjuvant chemotherapy to hormonal therapy is often considered questionable in patients with estrogen receptor-positive early breast cancer. Low risk of disease relapse after endocrine treatment alone and/or a low sensitivity to chemotherapy are reasons behind not all patients benefit from chemotherapy. Most of the patients could be exposed to unnecessary treatment- related adverse events and health care costs when treatment decision-making is based only on classical clinical histological features. Gene expression profile has been developed to refine physician's decision-making process and to tailor personalized treatment to patients. In particular, these tests are designed to spare patients the side effects of unnecessary treatment, and ensure that adjuvant chemotherapy is correctly recommended to patients with early breast cancer. In this review, we will discuss the main diagnostic tests and their potential clinical applications (Oncotype DX, MammaPrint, PAM50/Prosigna, EndoPredict, MapQuant Dx, IHC4, and Theros-Breast Cancer Gene Expression Ratio Assay).

Abstract A067: Oncotype DX assay has similar predictive accuracy for adverse pathology at radical prostatectomy in African American and European American men

Abstract Objective: To validate the 17-gene Oncotype DX Genomic Prostate Score (GPS) biopsy-based gene expression assay as a predictor of adverse pathology (AP: Pathologic Gleason score ≥4+3, presence of any Gleason 5, and/or ≥pT3) in African American (AA) men. Methods: Between February 2009 and September 2014, AA and European American (EA) men with very low, low, and intermediate risk prostate cancer (PCa) enrolled in a multi-institutional prospective study of vitamin D impacts of biopsy outcomes. The subset who proceeded to immediate radical prostatectomy (RP) after biopsy with available biopsy tumor blocks was included in a comparative effectiveness analysis of GPS on biopsy and its association with surgical AP on RP using logistic regression and receiver operating characteristic curves. Multiplicative interactions tested for differential prediction of GPS accuracy by race (AA vs. EA). Results: Overall, 102 AA and 76 EA men elected RP, out of which 51 (47.2%) had AP. GPS result was a significant predictor of AP (odds ratio per 20 GPS units [OR/20 units] in AA: 4.78; 95% CI 1.8-12.5, P =0.001; and EA: 4.41; 95% CI 1.6-11.9, P =0.003) in univariable analysis. On multivariate analysis, there was a significant interaction between GPS and race (P=0.01). On race stratified binary logistic regression, AP remained significant after adjustment for NCCN risk group in both AA and EA men (OR/20 units in AA: 3.29; 95% CI 1.2-9.1, P =0.02; and EA: 4.24; 95% CI 1.4-12.6, P =0.01). Area under the curves for AP using GPS/20 units was 0.719 for AAs vs. 0.745 for EAs (P=0.39). Conclusion: In this AA validation study, the Oncotype Dx PCa assay was confirmed as an independent predictor of AP at prostatectomy in AA and EA men with similar predictive accuracy, though there was evidence of effect modification by race. Citation Format: Samuel Carbunaru, Virgilia Marcias, Peter Gann, Roohollah Sharifi, Ximing Yang, Michael Dixon, Chase Gorbein, Borko Jovanovic, Andre Kajdacsy-Balla, Adam B. Murphy. Oncotype DX assay has similar predictive accuracy for adverse pathology at radical prostatectomy in African American and European American men [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A067.

Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18–30), or low-risk (0–17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- ( p = 0.84) and high-risk groups ( p = 0.92) with a statistically significant difference identified in the intermediate risk group ( p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

Adjuvant Chemotherapy for Patients with Breast Cancer Based on Clinical and Evolving Oncotype DX Criteria

Introduction: Oncotype DX assay recurrence score (ODX-RS) cut-off values have recently changed after the publication of the TAILOR-X trial results. We aim to explore decisions for adjuvant chemotherapy (ACT) based on physicians’ clinical assessment and the evolving ODX-RS. Methodology: Patients who underwent ODX testing after curative surgical resection of estrogen receptor positive (ER+), Her2 non-overexpressed (Her2–) and lymph node-negative (LN–) breast cancer (BC) were eligible. Management of these patients was guided by the results of the old ODX-RS-1 (<18, 18–30, and ≥31) risk grouping. For the purpose of this study, treatment decisions were also assumed according to TAILOR-X results (ODX-RS-2). Decisions of 3 medical oncologists on ACT were solicited by blinding them to the RS to investigate concordance with ODXA RS-1 and 2 recommendations. Results: Sixty-six consecutive patients were included. Median age was 50.5 (range: 21–73) years. There was 1 male patient, and 37/65 females (56.9%) were premenopausal. Among the 3 oncologists, recommendations for ACT based on clinical assessment were discrepant in 29 (43.9%) patients. Based on majority consensus (≥2 oncologists), ACT would have been recommended to 22/41 (53.7%) and 22/46 (47.82%) patients with low-risk tumors according to ODX-RS-1 and ODX-RS-2, respectively. Compared to ODX-RS-1, ODX-RS-2 identifies 12% (46 vs. 41) more low-risk patients and 66% (20 vs. 12 patients) more high-risk patients. Conclusion: Overtreatment and discrepancies in the management of patients with ER+/Her2–/LN– early BC can be minimized by the implementation of ODX genomic assay. Some differences in ACT recommendations exist between ODX-RS-1 and ODX-RS-2.

Abstract P3-14-05: Oncotype DX assay’s real world data in early stage breast cancer patients. Outcomes of a cohort treated in the Basurto University Hospital, Spain

Abstract Introduction: Oncotype DX (ODX) Recurrence Score (RS) is a gene-expression assay that provides prognostic and predictive information in hormonal-receptor positive (HR +), human epidermal growth factor receptor 2 negative (HER2-), axilary lymph node negative (LN-) disease. It estimates the 10 year-risk of distant recurrence and it is recommended to asses this issue and the potential benefit of adjuvant systemic therapy in early stage breast cancer (ESBC). (JCO 2016, NCCN 2019). Objective: To evaluate the impact of RS on our adjuvant treatment decision making and follow-up (FU). Materials and methods: Observational, prospective single institution study. Eligible patients (pts) were diagnosed between September 2012 and December 2018 with HR+, HER2 -, N0 and N+ (N1mic) ESBC for who underwent ODX assay. Criteria for ordered ODX assay were established by the group of experts from the Basque Country Health System. Treatment recommendations were documented before and after the conventional RS results. We reviewed clinical and pathology reports for FU and events. Descriptive statistics were used to summarize patient and tumor characteristics and changes in oncologists’ treatment recommendations. Mc Nemar’s test was used to identify how these tests impact in decisión. Results: N=337 pts. Median age was 57 years (SD 9,11); women 328 pts (97%); premenopausical 114 (34%); conservative surgery 271 pts (80%); sentinel node 318 pts (94 %); pN0: 248 pts (74%), pN1mic: 89 (26%); tumor size: pT1a-b: 41 pts (12 %), pT1c: 234 pts (69%) and pT2: 62 pts (18%); histologic type: ductal 280 pts (83%); histological grade: G1 49 pts (16%), G2 250 pts (74 %), G3 34 pts (10%); Ki 67 index &amp;gt;=13: 221 pts (66 %); progesterone receptors: positives: 304 pts (90%); presence of lymphovascular invasión:36 pts (11%). Treatment decision before assay was hormonal therapy (HT) in 242 pts (72 %) and chemotherapy (CT) in 95 pts (28 %). Conventional RS were: low risk RS&amp;lt;18 (LR): 180 pts (53%), intermediate risk RS 18-30 (IR): 135 pts (40%) and high risk RS &amp;gt;30 (HR): 22 pts (7%). TAILORx RS cutpoints were: LR RS &amp;lt;11: 78 pts (23%), IR RS 11-25: 207 pts (61%), HR RS &amp;gt;25: 52 pts (15%). Post-assay treatment: 278 pts (82.5%) received HT and 59 pts (17.5 %) CT. Treatment recomendation pre and post ODX assay changed in 17,5% of pts: in 10,5% from CT to HT and 7% from HT to CT. The McNemar's test was significant value (0.000). With a median FU of 35 months (range 1-77) there were 5 events: (1.5%): 1 local (0.3%) and 4 distant (1.2%). Conclusions: In our cohort, the 82.5% of pts received HT. The treatment decisión changed 17.5% of pts. The ODX avoided CT in 10.5% of 38 pts (28% pre and 17.5% post). At this time, insufficient median FU and number of events are available to examine long-term prognosis and CT benefit. Citation Format: Maria Purificacion Martínez del Prado, Borja López de San Vicente, Juan Fernando Arango Arteaga, Jairo Legaspi Folgueira, Ane Zumárraga Cuesta, Fernando Pikabea Diaz, Patricia Novas Vidal, María López Santillán, Laura Sande Sardina, Maitane Nuño Escolástico, María Teresa Abad Villar, Maria Ángeles Sala Gonzalez, Covadonga Figaredo Berjano, María Teresa Pérez Hoyos, Elena Galve Calvo. Oncotype DX assay’s real world data in early stage breast cancer patients. Outcomes of a cohort treated in the Basurto University Hospital, Spain [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 P3-14-05.

Abstract OT3-17-03: Impact of the Oncotype DX breast cancer assay on treatment decisions in a UK population of patients with oestrogen receptor positive early breast cancer with 1-3 lymph nodes positive who are candidates for chemotherapy, but for whom the benefits are uncertain - Interim results

Abstract Introduction: The addition of adjuvant chemotherapy to hormonal therapy is recommended for patients with lymph node-positive (LN+ve), estrogen receptor positive (ER+), HER2-ve early breast cancer, despite the fact that many women will remain disease-free even if they do not receive chemotherapy. Therefore, a number of patients with LN+ EBC may be unnecessarily exposed to the toxicities of chemotherapy with no treatment benefit. In the UK, the Oncotype DX® Recurrence Score (RS) is recommended by NICE for routine testing in patients with ER+ HER2-ve, lymph node negative early stage breast cancer. Approximately 32% of newly diagnosed breast cancer patients will have lymph node involvement but do not have distant metastasis at the time of diagnosis. Objectives: Primary objective is to characterize how the results on the Oncotype DX® assay impact the decision-making process of physicians in the UK for women with ER+ HER2-ve EBC with 1-3 lymph nodes involved who are potential candidates for chemotherapy, but for whom the benefits may be uncertain. Secondary objectives include; (1) Assess the impact of the Oncotype DX RS in clinical practice in patients with 1-3 lymph nodes positive EBC, (2)Analyse distribution of RS and (3)Observe the percentage of patients not receiving chemotherapy as a result of the Oncotype DX RS. Methods: Postoperative patients with lymph node positive disease: N=720. Micrometastasis = 70patients, 1 Lymph Node Positive = 400patients, 2 Lymph Node Positive = 200patients &amp; 3 Lymph Node Positive = 50patients (exploratory analysis). Study start date October 2017 to projected study end date of December 2021. INTERIM Results: To date, 194 patients have entered the Oncotype DX Node POS Study since October 2017 from 13 recruiting institutions across the UK. The nodal status is as follows; micrometastasis = 21patients (10%), 1 lymph node positive = 103 patients (53%), 2 lymph node positive = 53 patients (27%) and 3 lymph node positive =17 patients (9%). The average age of patient was 57.5years (range 27-79). Of 194 patients, 189 have received a recurrence score in the 1-3 lymph node positive setting. Average RS was 13.8 (range 0-63). Micrometastasis category received an average RS of 15, 1 LN+ve category received an average RS of 15.5, 2 LN+ve category received an average RS of 15.8 and 3 LN+ve category received an average RS of 20.8. Of 189 patients the decision to administer chemotherapy changed in 140 patients (74%) once the Oncotype DX score had been received. Decision to administer chemotherapy remained the same in 49 patients (26%). This shows that Oncotype DX greatly alters the decision-making process in patients with 1-3 LN+ve, despite the trial not setting a chemotherapy cut-off score. Those patients who received a recurrence score of 18 or below = 129 (68%). Patients who received a recurrence score of above 18 = 60 (32%). The largest nodal category (1 LN+ve) witnessed the highest rate of patients receiving a RS of below 18 (70%), followed by 2 LN+ve (66%) and 3 LN+ve (43%). One patient with 2 lymph nodes positive received a RS of zero. Weak correlation was observed between histopathological factors and recurrence score. Conclusion: Interim results show the use of the Oncotype DX assay in patients with 1-3 lymph node-positive (LN+ve), ER+ HER2-ve, EBC significantly alters the decision-making process in guiding use of chemotherapy. Result show that 74% of patients were spared chemotherapy where there was deemed to be no additional benefit over hormonal therapy alone. This resulted in 140 patients being spared the unnecessary side effects and exposure to toxicities of chemotherapy. This also prevented overtreatment of patients from a healthcare economic cost perspective. Citation Format: Daniel Thomas, William Maxwell, Caroline Archer, Anne Rigg, Tamas Hickish, Jo Dent, Laura Pettit, Marianne Dillon, Christy Goldsmith, Mark Verrill, Ludger Barthelmes, Saira Khawaja, Yousef Sharaiha, Mark Davies, Fawaz Arikat, Sahail Khan, Asma Munir, Anita Huws, Simon DavidHenry Holt. Impact of the Oncotype DX breast cancer assay on treatment decisions in a UK population of patients with oestrogen receptor positive early breast cancer with 1-3 lymph nodes positive who are candidates for chemotherapy, but for whom the benefits are uncertain - Interim results [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 OT3-17-03.

Factors That Predict Biological Aggressiveness in Estrogen Receptor-Positive / Human Epidermal Growth Factor Receptor 2-Negative / Lymph Node-Negative Breast Cancer.

Background: Traditionally, breast cancer is staged using TNM criteria: tumor size (T), nodal status (N), and metastasis (M). The Oncotype DX assay provides a recurrence score (RS) based on genomics that predicts the likelihood of distant recurrence in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2–)/lymph node–negative (LN–) tumors.Methods: We retrospectively reviewed the medical records of patients with ER+/HER2–/LN– breast cancer tumors who were evaluated between 2007 and 2017 with Oncotype DX RS. We compared the RS to tumor size, patient age, progesterone receptor (PR) status, and LN immunohistochemistry to assess for factors that may independently predict recurrence risk. We also compared tumor size to tumor grade.Results: The data set included 296 tumors: 248 ER+/PR-positive (PR+)/HER2– and 48 ER+/PR-negative (PR–)/HER2–. RS ranged from 0 to 66, patient age ranged from 33 to 77 years, and tumor size ranged from 1 to 65 mm. No significant correlation was found between age and RS (r=–0.073, P=0.208). PR– tumors had a significantly higher RS regardless of size (PR– mean RS 30.8 ± 12.7; PR+ mean RS 16.3 ± 7.3; t(53)=7.6, P<0.0001). No significant correlation was seen between tumor size and RS for all tumors (r=–0.028, P=0.635), and this finding remained true for the PR+ tumor subgroup (r=0.114, P=0.072). However, a significant negative correlation was seen between tumor size and RS in the PR– subgroup (r=–0.343, P=0.017). Further analysis to ensure that differences in tumor grade did not account for this correlation showed equal distribution of well differentiated, moderately differentiated, and poorly differentiated tumors with no significant correlation between tumor size and grade.Conclusion: Increasing tumor size may not be associated with increasing biological aggressiveness. Traditionally, smaller tumors are thought to be lower risk and larger tumors higher risk, with a tendency to use chemotherapy with large tumors. However, our data showed a negative correlation between tumor size and RS in the PR– subgroup. A tumor with PR negativity that reaches a large size without metastasizing may suggest a favorable tumor biology. These tumors may not receive as much benefit from chemotherapy as previously thought. Also, the higher RS seen in smaller PR– tumors may demonstrate PR– status as a predictor for higher risk of distant recurrence. We propose that all tumors meeting the ER+/PR–/LN– criteria, regardless of size, should be considered for genotyping, with the RS used to guide chemotherapy benefit.

Oncotype DX Breast Cancer recurrence score resists inter-assay reproducibility with RT2-Profiler Multiplex RT-PCR

The Oncotype Dx assay is frequently used to test if breast cancer patients can be spared from chemotherapy without negative effects for their future clinical course. However, due to conflicting data on the assay utility, in the recent past its reimbursement situation in Germany was revised; due to continued requests by clinicians for predictive values, our group decided to implement an Oncotype Dx like alternative assay with the objective of obtaining quality and cost optimization. Customized RT2-Profiler assays covering the 21 gene panel of the Oncotype Dx assay were applied to a pilot cohort of breast cancer patients with known Oncotype Dx Recurrence Score (RS). The Ct values obtained with RT2-Profiler-assays were used to calculate the unscaled Recurrence Score (RSu) values and the thereon based RS according to the Oncotype DX assay rules if available. Despite consistent assay performance it was impossible to establish correlations between RT2-Profiler recurrence scores with the respective Oncotype DX values not to mention exact matches. By following the Oncotype DX assay and its interpretation as close as possible we faced several obstructions such as lack of information on RNA amount used, missing units in the single gene expression report, missing references cited in the original study that should explain the determination of the recurrence score formula, and vague information on the normalization of the gene expression impeding the reproduction of Oncotype Dx results in other laboratories. Unfortunately, the Oncotype Dx assay cannot be confirmed by the customized RT2-profiler assay, not least because of the fact that the individual gene measurements are not provided in the medical report, although these are mandatory for the RS calculation. In fact, the “single gene report” only contains unscaled scores of the ER, PR, and Her2 genes without any internationally accepted unit used to describe a transcript quantity. Therefore a direct comparison with the in-house measurement to evaluate its performance is impossible. With regard to our findings and the fact that the Oncotype RS represents a likelihood of the risk of relapse it thus remains impossible to assess the clinical necessity of this assay.

209P - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals

BackgroundBenefit derived from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients (pt) with hormone-receptor–positive HER2 negative early breast cancer. The 21-gene recurrence-score (RS) assay Oncotype DX, provide prognostic and predictive information. Results of the TAYLORx study have confirmed that most of patients with negative node status and RS>25 can avoid CT without increasing their risk of relapse. However, pt<50 years (y) and RS>20 showed benefit with CT. MethodsAim: To analyse the impact of age using RS test to change the indication of adjuvant CT and the relationship between different clinical pathological factors and the RS value. We analysed 240 cases out of 251 RS test performed in the 3 ICO Centers during 2017-2018. We compared the adjuvant treatment initially planned according to institutional protocol with the treatment given after RS in the total cohort and in pt<50 y. We performed a logistical regression analysis of pathological factors and RS. ResultsCT was indicated in all pt before knowing the RS results. Only 46pt (19%) received CT after RS results. 14 out of 88pt < 50 y received adjuvant CT (15%). 15pt <50 y had a RS between 21-25, only 5 of them received CT, because in most of them, the RS was performed prior TAILORx results were published. Nowadays, all of these 15pt would had received CT: 61/240 (25%). Clinical-pathological characteristics of the series are summarized in the Table. Of the risk factors analysed, only Ki67>25 (<0.001) and PR≤20% (0.01) showed a statistically significant relationship with a higher probability of RS>25 in a multivariate analysis.Table209PTableAge median (range)53 (19-76) <50 y 35.1% ≥50 y 64.9%Tumor size median15mmHistological gradeG1 23% G2 69.7% G3 4.4%Progesterone receptor≤20% 21% >20% 78%Ki67 median (p25-75)20 (13,28) ≤14 27% 14-25 41% >25% 31%Nodal statuspN0 57%pN1mic 15%pN1a 27% Conclusions82% of pt of our series could avoid CT, however this proportion change after TAYLORx results in younger patients. Today 75% of these pt would had avoided CT. Ki67 > 25% and Progesterone Receptor ≤20% were the only pathological factors associated with an increased risk of RS>25. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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

ObjectivesThe 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. MethodsUsing 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. ResultsWe 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 between $162 million and $1.1 billion at willingness-to-pay thresholds of $150 000 to $200 000/quality-adjusted life years. ConclusionFuture research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.

Diffusion-weighted MRI of estrogen receptor-positive, HER2-negative, node-negative breast cancer: association between intratumoral heterogeneity and recurrence risk

To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay. This retrospective study was conducted on 105 women (median age, 48years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated. Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600× 10-3mm2/s vs. 0.746 × 10-3mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors. The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer. • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.

The Oncotype Dx Assay in ER-Positive, HER2-Negative Breast Cancer Patients: A Real Life Experience from a Single Cancer Center.

To determine the influence of the Oncotype Dx assay on the treatment of patients with Estrogen Receptor (ER)-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative, axillary lymph node-negative or micrometastatic carcinoma of the breast in a single cancer center. In addition, patients with intermediate Oncotype Dx recurrence scores were analyzed to assess the factors influencing therapeutic decisions for adjuvant chemotherapy. Data from medical records of women diagnosed with carcinoma of the breast and qualified for the Oncotype Dx assay were extracted (OncoDx cohort). Patient demographic and cancer characteristics, genomic report, and course of treatment data, including survival outcomes and treatment decision-making, were analyzed. A matched cohort of patients with similar tumor stage and biology (ER-positive, HER2-negative) from the era before the introduction of the Oncotype Dx assay was analyzed for comparison (pre-OncoDx cohort). Two hundred and one patients were included in the OncoDx cohort and one hundred and sixty patients were included in the pre-OncoDx cohort. Oncotype Dx recurrence score (RS) was low (<11) in fifty-six patients (28%), intermediate (11-25) in one hundred and twenty-three patients (61.5%) and high (>25) in twenty one patients (10.5%). Demographic and cancer clinicopathologic characteristics between OncoDx and pre-OncoDx cohorts were similar. Overall, 10.9% of the patients in the OncoDx cohort received adjuvant chemotherapy, versus 23.8% of the patients in the pre-OncoDx cohort (Fisher exact p=0.003). Fewer patients were recommended adjuvant chemotherapy in the OncoDx era compared to the pre-OncoDx era (17.9% vs 30.6%, respectively, Fisher exact p=0.006). The decision to recommend chemotherapy within the intermediate-risk cohort was influenced by the patient's RS. The mean RS of patients in the intermediate-risk cohort who did not receive chemotherapy was 21.5 while the score of those that received chemotherapy was 24.6 (p=0.000). The series confirmed excellent PFS and OS for both OncoDx and pre-OncoDx cohorts. This single cancer center analysis confirms the avoidance of chemotherapy in the great majority of patients with early ER-positive, HER2-negative, lymph node-negative or micrometastatic carcinoma of the breast since the introduction of the Oncotype Dx assay. A higher recurrence risk score within the intermediate group may influence the decision for chemotherapy inclusion in the adjuvant treatment plan. A lower PR percentage by IHC and higher grade may predict higher Oncotype Dx scores.

Genomic classifiers for treatment selection in newly diagnosed prostate cancer.

To review systematically the literature on genomic tests for prostate cancer (PCa) and to evaluate the current state of the evidence on their use in patients with newly diagnosed PCa. We conducted a systematic review by searching PubMed, Embase, Cochrane Central and conference abstracts from the American Urological Association, published between 2010 and 2018. Studies evaluating Prolaris, Oncotype Dx and Decipher assays were assessed for inclusion by two authors. Studies were excluded if the results were derived from surgical specimens rather than biopsy specimens. A meta-analysis was not performed owing to significant variations in methodologies, definitions and outcome measures. A total of 729 articles were retrieved in our initial search. After removing duplicates (270) and excluding articles deemed not relevant (432), 21 full-text articles were deemed suitable for inclusion in the present analysis. The full-text articles comprised eight studies on Prolaris, eight studies on Oncotype Dx and five studies on Decipher. For each genomic test we extracted data regarding the risks of adverse pathology, biochemical recurrence, metastasis and PCa-specific mortality. The results of genomic tests that use biomarkers derived from prostate biopsy can be used in conjunction with clinicopathological variables to improve our ability to risk-stratify patients with newly diagnosed PCa. Additional data are needed on the impact of using these tests on long-term patient outcomes and their cost-effectiveness.

Radiomics signature on 3T dynamic contrast-enhanced magnetic resonance imaging for estrogen receptor-positive invasive breast cancers: Preliminary results for correlation with Oncotype DX recurrence scores.

To evaluate the ability of a radiomics signature based on 3T dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to distinguish between low and non-low Oncotype DX (OD) risk groups in estrogen receptor (ER)-positive invasive breast cancers.Between May 2011 and March 2016, 67 women with ER-positive invasive breast cancer who performed preoperative 3T MRI and OD assay were included. We divided the patients into low (OD recurrence score [RS] <18) and non-low risk (RS ≥18) groups. Extracted radiomics features included 8 morphological, 76 histogram-based, and 72 higher-order texture features. A radiomics signature (Rad-score) was generated using the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate logistic regression analyses were performed to investigate the association between clinicopathologic factors, MRI findings, and the Rad-score with OD risk groups, and the areas under the receiver operating characteristic curves (AUC) were used to assess classification performance of the Rad-score.The Rad-score was constructed for each tumor by extracting 10 (6.3%) from 158 radiomics features. A higher Rad-score (odds ratio [OR], 65.209; P <.001), Ki-67 expression (OR, 17.462; P = .007), and high p53 (OR = 8.449; P = .077) were associated with non-low OD risk. The Rad-score classified low and non-low OD risk with an AUC of 0.759.The Rad-score showed the potential for discrimination between low and non-low OD risk groups in patients with ER-positive invasive breast cancers.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx

This focused update addresses the use of Oncotype DX in guiding decisions on the use of adjuvant systemic therapy. ASCO uses a signals approach to facilitate guideline updating. For this focused update, the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease-free survival in women with Oncotype DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Oncotype DX assay to assess for evidence of clinical utility. For patients with hormone receptor-positive, axillary node-negative breast cancer whose tumors have Oncotype DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Predictors of adjuvant chemotherapy for breast cancer patients with an intermediate Oncotype-DX score: A SEER-based population study.

e12014 Background: Oncotype-DX Assay is a 21-gene based recurrence score (RS) that helps stratify breast cancer patients based on their risk of recurrence. It is often used to help identify patients that may benefit from adjuvant chemotherapy (AC). Prior to the TAILORx Trial results, there were no guidelines for AC in patients with an intermediate score (18-30). Management of these patients was often at the clinical judgement of the provider. We sought to determine predictors of AC among these patients, and measure treatment effect on survival. Methods: We queried the Surveillance, Epidemiology, and End-Results database for breast cancer patients newly diagnosed between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative breast cancer with an intermediate RS. Male patients, those younger than 40 years, tumors 5 mm or less, and incomplete records were excluded. Univariate and multivariate analysis was performed to derive independent predictors of AC. Cox Proportional-Hazards Model was done to examine the effect of AC on survival. Results: We included 14,710 patients of whom 4,508 (30.6%) received AC. Patients that received AC were younger (55.4 years [8.8] vs 60.0 [9.7], p &lt; 0.001), grade III or higher (29.8% vs 16.4%, p &lt; 0.001), and had a higher RS (23.9 [3.6] vs 21.5 [3.1], p &lt; 0.001). Higher T stage was associated with a higher rate of patients receiving AC (p &lt; 0.001). Marital status was also associated with AC; a higher proportion of patients who received AC were married (67.9% vs 64.4%, p &lt; 0.001). There was no significant association between race/ethnicity or insurance type with AC. Multivariate analysis showed that RS (OR: 1.24 [1.23-1.26], p &lt; 0.001), T stage (OR: 1.67 [1.21-2.30], p &lt; 0.001), and a grade III tumor (OR: 1.85 [1.64-2.09], p &lt; 0.001) were the strongest predictors of AC. The age decile 80-89 years (OR: 0.05 [0.02-0.10], p &lt; 0.001) was the most negative predictor of AC. AC did not have an effect on 5 year overall survival (97.6% vs 96.0%, p = 0.28). Conclusions: Between 2010-2015, our study shows 30.6% of breast cancers patients with an intermediate Oncotype-DX score were given AC. The decision to treat was largely based on tumor size, grade and age. AC had no effect on overall survival.