Oncotype DX Testing Research Articles

Evaluation of the role of pharmacy technicians in reviewing the eligibility for Oncotype DX genomic test and the impact of the test on treatment plans in breast cancer patients.

The Oncotype DX genomic test is a treatment decision-making tool. Test results are presented as recurrence scores which are used to help decide between adjuvant hormonal therapy (low recurrence score) or chemotherapy (high recurrence score). Since 2014, the Oncotype DX test has been funded at the cancer treatment centres in our province for patients with early breast cancer. Eligibility criteria for funding include patient and tumour characteristics. Pharmacy technicians were assigned to review and approve requests based on the eligibility criteria and with access to consultation to an oncology pharmacist and a medical oncologist. We assessed the clinical role of pharmacy technicians in this review process and the impact of recurrence score on treatment decisions. This was a retrospective, multi-centre study to evaluate the Oncotype DX test eligibility review process from June 2014 to May 2015. The main objectives were to assess (1) the discrepancy rate of approval by the pharmacy technicians in this review process and (2) the concordance rate between the recurrence score from the Oncotype DX test and the adjuvant treatment given. Four hundred and forty requests for Oncotype DX test were received during the study period. A total of 90.8% of requests were approved and 9.2% were denied. The discrepancy rate of approval by pharmacy technicians was 1.1%. The average review time was 13.8 min, with the reviewing pharmacist and oncologist consulted in 5.5 and 15.2% of the requests, respectively. The concordance rate between the recurrence score and given treatment was 96%. The discrepancy rate of our pharmacy technicians appears to be similar to that reported with other expanded technician roles in literature, suggesting that the current task and other similar clinical tasks can be reliably delegated to technicians. The concordance rate of the recurrence score and given treatment in our study was higher than what has been reported in literature, suggesting that most of our patients were treated in accordance to recurrence score-based recommendations. Pharmacy technicians were able to expand their clinical role by accurately reviewing the Oncotype DX test requests with a low discrepancy rate. The Oncotype DX test results appeared to successfully guide the adjuvant treatment given to patients in accordance to recurrence score-based recommendations.

Are Pathological Parameters in Breast Carcinoma Underestimated? Results Correlation in Comparison With Oncotype Dx Testing in Breast Carcinoma Patients in Saudi Arabia

Are Pathological Parameters in Breast Carcinoma Underestimated? Results Correlation in Comparison With Oncotype Dx Testing in Breast Carcinoma Patients in Saudi Arabia

Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence score.

Oncotype Dx is a genetic test that has been incorporated into the 2017 AJCC breast cancer staging system for ER positive, HER2-negative, lymph node-negative patients to predict the risk of recurrence. Recent data suggest that immunohistochemistry (ER, PR, HER2, and Ki-67) and histologic subtype may identify patients that will not benefit from Oncotype Dx testing. A total of 371 patients underwent Oncotype Dx testing at our institution from 2012 to 2016. Oncotype recurrence score was categorized as low- (ORS=0-10), intermediate- (11-25), or high risk (26-100). Invasive carcinomas were categorized based on histologic subtype as "favorable" (mucinous, tubular, cribriform, tubulolobular, and lobular) and "unfavorable" (ductal, mixed ductal and lobular, and micropapillary carcinoma). All cases were estrogen receptor positive and HER2-negative. Clinical and histologic predictors of low-risk ORS were assessed in univariate and multivariate logistic regression. A total of 371 patients were categorized by ORS as low risk (n=85, 22.9%), intermediate risk (n=244, 65.8%), and high risk (n=42, 11.3%). The histologic subtypes with the highest percentage of high-risk ORS were invasive micropapillary (n=4/17, 23.5%), pleomorphic lobular (n=2/10, 20%), and ductal carcinoma (n=28/235, 11.9%). Low-grade invasive carcinomas with favorable histology rarely had a high-risk ORS (n=1/97, 1%). In a simple multivariable model, favorable histologic subtype (OR=2.39, 95% CI: 1.10 to 5.15, P=0.026), and histologic grade (OR=1.76, 95% CI: 1.07 to 2.90, P=0.025) were the only significant predictors of an ORS less than 11 in estrogen receptor positive, HER2-negative, and lymph node-negative patients. We question the utility of performing Oncotype Dx in subtypes of invasive carcinoma that are associated with excellent prognosis. We propose that immunohistochemistry for ER, PR, and HER2 is sufficient for patients with low-grade invasive carcinomas and can be used as a surrogate for Oncotype Dx.

Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.

For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention. We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing. The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt. Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation. This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.

Oncotype DX testing of ≥2 tumours not cost effective

Oncotype DX testing of ≥2 tumours not cost effective

Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer

BackgroundGene-expression companion diagnostic tests, such as the Oncotype DX test, assess the risk of early stage Estrogen receptor (ER) positive (+) breast cancers, and guide clinicians in the decision of whether or not to use chemotherapy. However, these tests are typically expensive, time consuming, and tissue-destructive.MethodsIn this paper, we evaluate the ability of computer-extracted nuclear morphology features from routine hematoxylin and eosin (H&E) stained images of 178 early stage ER+ breast cancer patients to predict corresponding risk categories derived using the Oncotype DX test. A total of 216 features corresponding to the nuclear shape and architecture categories from each of the pathologic images were extracted and four feature selection schemes: Ranksum, Principal Component Analysis with Variable Importance on Projection (PCA-VIP), Maximum-Relevance, Minimum Redundancy Mutual Information Difference (MRMR MID), and Maximum-Relevance, Minimum Redundancy - Mutual Information Quotient (MRMR MIQ), were employed to identify the most discriminating features. These features were employed to train 4 machine learning classifiers: Random Forest, Neural Network, Support Vector Machine, and Linear Discriminant Analysis, via 3-fold cross validation.ResultsThe four sets of risk categories, and the top Area Under the receiver operating characteristic Curve (AUC) machine classifier performances were: 1) Low ODx and Low mBR grade vs. High ODx and High mBR grade (Low-Low vs. High-High) (AUC = 0.83), 2) Low ODx vs. High ODx (AUC = 0.72), 3) Low ODx vs. Intermediate and High ODx (AUC = 0.58), and 4) Low and Intermediate ODx vs. High ODx (AUC = 0.65). Trained models were tested independent validation set of 53 cases which comprised of Low and High ODx risk, and demonstrated per-patient accuracies ranging from 75 to 86%.ConclusionOur results suggest that computerized image analysis of digitized H&E pathology images of early stage ER+ breast cancer might be able predict the corresponding Oncotype DX risk categories.

Regional audit: Oncotype DX testing in intermediate recurrence risk, early breast cancer patients

Regional audit: Oncotype DX testing in intermediate recurrence risk, early breast cancer patients

Is Oncotype DX test necessary for T1b grade 1, hormone receptor positive HER-2 negative breast cancer? A single institution retrospective analysis.

e12598Background: NCCN (National comprehensive cancer network) recommends to consider Oncotype DX testing for patients diagnosed with stage IA breast cancers between 0.5- 1 cm that are hormone receptor positive and HER-2 negative. This study is a retrospective review of patients diagnosed with T1b stage IA breast cancers diagnosed at Cone Health Cancer Center between 2012 and 2017 who had Oncotype DX testing. Methods: Patients with T1b hormone receptor positive and HER-2 negative breast cancer, who had Oncotype DX testing performed were queried from tumor registry from 2012 to 2017. The registry also provided information regarding the grade and whether these patients received chemotherapy. Results: A total of 73 patients with T1b N0 (stage IA ) invasive breast cancers that were ER and PR positive and HER-2 negative between 2012 and 2017, had Oncotype DX test performed. Along these, 12 patients received adjuvant chemotherapy. Among those patients receiving adjuvant chemotherapy, 9 patients had Oncotype DX ...

Long-term outcomes in women with low-risk hormone-sensitive early-stage breast cancer.

e12583Background: Oncotype DX test is useful in the identification of women who have a low risk of recurrence and can safely avoid chemotherapy. However, there are persistent gaps in knowledge on t...

Cost effectiveness analysis of Oncotype DX testing in patients with synchronous unilateral primary breast cancer.

e12555Background: Oncotype DX is a commercial diagnostic test used to predict the likely benefit from chemotherapy in ER+ HER2- node- breast cancer. Patients with multiple, synchronous ipsilateral ...

Selection for Oncotype Dx testing among young women with early-stage ER+/HER2- breast cancer.

533Background: The Oncotype Dx Recurrence Score (RS) predicts distant recurrence risk and benefit from chemotherapy for women with early-stage estrogen receptor (ER) positive (+)/human epidermal gr...

Uptake of BRCA 1/2 and oncotype DX testing by medical and surgical oncologists.

The diffusion of genomic testing is critical to the success of precision medicine, but there is limited information on oncologists' uptake of genetic technology. We aimed to assess the frequency with which medical oncologists and surgeons order BRCA 1/2 and Oncotype DX testing for breast cancer patients. We surveyed 732 oncologists and surgeons treating breast cancer patients. Physicians were from Florida, New York, New Jersey, and Pennsylvania, and were listed in the 2010 AMA Masterfile or identified by patients. 80.6% of providers ordered BRCA 1/2 testing at least sometimes and 85.4% ordered Oncotype DX (p = 0.01). More frequent ordering of BRCA 1/2 was associated with more positive attitudes toward genetic innovation (OR 1.14, p = 0.001), a belief that testing was likely to be covered by patients' insurance (OR 2.84, p < 0.001), and more frequent ordering of Oncotype DX testing (OR 8.69, p < 0.001). More frequent use of Oncotype DX was associated with a belief that testing was likely to be covered by insurance (OR 7.33, p < 0.001), as well as with more frequent ordering of BRCA 1/2 testing (OR 9.48, p < 0.001). Nearly one in five providers never or rarely ever ordered BRCA 1/2 testing for their breast cancer patients, and nearly 15% never or rarely ever ordered Oncotype DX. Less frequent ordering of BRCA 1/2 is associated with less frequent use of Oncotype DX testing, and vice versa. Those who do not order BRCA 1/2 testing report less positive attitudes toward genetic innovation. Further education of this subset of providers regarding the benefits of precision medicine may enable more rapid diffusion of genetic technology.

Abstract P6-09-10: Provider characteristics and receipt of oncotype Dx testing in women diagnosed with early stage breast cancer using SEER-Medicare data

Abstract Background: Oncotype DX (ODX) genomic testing to evaluate recurrence risk and benefit of adjuvant chemotherapy in patients with ER-positive, node-negative breast cancers was approved for Medicare reimbursement in 2006. We previously examined patient-level factors associated with utilization of ODX testing from 2005-2009 in the SEER-Medicare population; ODX testing occurred most frequently in patients with ER+, node negative disease, with 80% of all tests occurring in patients aged 66-75. In our current study, we examined potential provider factors associated with patient-level ODX testing from 2008 to 2012. Methods: Using a retrospective cohort design, we identified all individuals who had a SEER diagnosis of breast cancer from 2008-2011 and were enrolled in fee-for-service Medicare parts A and B for one year before and one year after diagnosis. We limited our analysis to individuals who had surgical resection of their breast tumor within 4 months of diagnosis and had a breast tumor which was ER+, invasive, and non-metastatic to capture the eligible patient population. Using Medicare claims data linked with the AMA physician dataset (which includes AMA members and non-members), we identified physician characteristics of the primary breast surgeon and medical oncologist including specialty, gender, years in practice, case volume, utilization of chemotherapy, and whether they serve rural populations. For patients with an ODX test, we used the identification on the claim to link to the performing provider. We examined the associations between provider characteristics and patient receipt of ODX testing using unadjusted and adjusted logistic regression models. Adjusted models included patient demographic and clinical characteristics. Results: We identified 24,463 eligible breast cancer patients who received their care from 3172 primary surgeons and 2475 medical oncologists. Of 4124 ODX tests ordered for patients in the study, 70% were ordered by the assigned medical oncologist and 16% were ordered by the breast surgeon. In multivariable regression models, multiple physician characteristics were associated with receipt of ODX testing including having an assigned medical oncologist (OR 2.77, 95% CI 2.00-3.82), having a surgeon with a specialty of surgical oncology (OR 1.20, 95% CI 1.09-1.31), having a female medical oncologist (OR 1.10 95% CI 1.02-1.20). Having a medical oncologist with ≥5 years in practice was associated with lower odds of testing (OR 0.83 95% CI 0.76-0.92). Breast surgery performed at an academic hospital was associated with higher odds of ODX testing (OR 1.11 95% CI 1.02-1.20). Conclusion: The majority of ODX testing for indicated breast cancer patients is ordered by medical oncologists, though surgeons and physicians of other specialties also order the tests in practice. Physician characteristics including gender and time in practice appear to affect a patient's likelihood of receiving ODX testing, creating opportunities for targeting interventions to help women with breast cancer receive optimal care. Citation Format: Dinan MA, Wilson LE, Greiner M, Pollack CE. Provider characteristics and receipt of oncotype Dx testing in women diagnosed with early stage breast cancer using SEER-Medicare data [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 P6-09-10.

Abstract P2-10-10: Oncotype Dx testing in patients with synchronous unilateral primary breast cancer

Abstract Introduction: Oncotype DX, is a commercial diagnostic test that is used to predict the likely benefit from chemotherapy in ER+, HER2-negative, node-negative breast cancer. Patients with multiple, synchronous ipsilateral primary breast cancers often have &amp;gt;1 tumor tested if results from the first tumor show low or intermediate recurrence scores. Whether this approach is cost effective is unknown. Methods: We reviewed Oncotype Dx results for 907 ER+/HER2- breast cancer patients seen at Rush University Medical Center from 2/2006 to 10/2016. Thirty-nine patients (35 with the same histology) had multiple, synchronous unilateral tumor samples tested. Results were reported both on the numeric risk score associated with the test and the categorized result (low/intermediate/high) recurrence risk. For patients undergoing more than 2 tests, the first two were arbitrarily chosen for the paired analysis. Descriptive statistics were used to examine the risk score distributions and assess potential correlation between paired samples. Statistical inference methods included estimating the correlation coefficient, regression models predicting one score with another, and evaluating the paired score differences with respect to mean deviation from zero. For categorized risk score, analysis evaluating category concordance between tumors was used to assess the degree of agreement. Analyses were conducted on all patients, and a subset consisting of patients whose two tumors had the same histology, where scores may be expected to exhibit greater concordance. Results:Categorical risk score (RS): The concordance rate for risk category was 77% (30/39 patients) and Kendall's tau measure of association = 0.57, and was further increased to 80% (28/35 patients) and tau 0.63 for tumors with the same histology. Only one patient had tumor samples with low and high RS. A second patient had tumor samples with intermediate and high RS. Continuous RS: The correlation was 0.81 (p &amp;lt; 0.0001). For tumors with the same histology, correlation increased to 0.83, with regression r2 (predicting second tumor RS value with first) = 0.69, indicating that the majority of variation in second score can be explained by variation in first score. Conclusion: Oncotype Dx testing in patients with synchronous, unilateral primary breast cancers generally results in concordant results, even more so when the tumor samples are of the same histology. In our study, only 1 of the 39 patients had discordant low/high tumor pairs. Continuous scale tumor RS scores were highly correlated (&amp;gt; 0.8). Therefore the benefit of testing additional samples appears marginal and, with the $4,620 cost per test, may not be cost-effective. Citation Format: Clark M, Coggan J, Dignam J, Rao R, Usha L, Kabaker K, Cobleigh M. Oncotype Dx testing in patients with synchronous unilateral primary breast cancer [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 P2-10-10.

Abstract P1-07-21: Relationship between hereditary cancer syndromes and oncotype DX recurrence score

Abstract Background Oncotype DX Recurrence Score (RS) is used to stratify breast tumors into those likely to respond to cytotoxic chemotherapy. Women and men with hereditary cancers tend to have tumors that are chemosensitive. We hypothesize that a high RS may harbor a signal of potential hereditary risk. This analysis aims to identify whether breast cancer patients with hereditary cancer syndromes have a disproportionate amount of high RS compared to sporadic cases. Methods Individuals with a personal history of breast cancer who received treatment at participating research facilities and had hormone receptor positive breast cancer, Oncotype DX testing and hereditary cancer mutation testing were included. Oncotype DX RS was recorded along with the type of genetic testing and the genetic testing results. RS was categorized as low (0-17), intermediate (18-30), and high (31+). Those with deleterious mutations in any known hereditary cancer gene were considered positive. Individuals with a variant of uncertain significance (VUS) or negative genetic testing result were considered negative. Difference in distribution of tumors with low, intermediate, and high Oncotype DX results in those with hereditary breast cancers compared to those with sporadic breast cancers was determined with Chi-square. Results 419 patients with Oncotype DX testing from two clinical sites were collected from 2013. Of those, 123 underwent genetic risk assessment. Mutations identified included the following genes: BRCA1 (1), BRCA2 (5); CHEK2 (3); BRIP1 (3); NBN (2); MSH6 (1). Of those testing positive for a deleterious mutation, the number of patients with RS results in each category were 5, 4 and 6 for low, intermediate and high, respectively. For those considered negative on hereditary cancer panel testing, the RS results were 76, 52 and 8, respectively. Of those with high RS, 43% had deleterious mutations. Chi square test was statistically significant for a difference between the RS of those with deleterious hereditary mutations versus those with sporadic cancers (p = 0.000086). Conclusions High RS may indicate a higher likelihood of harboring a hereditary cancer syndrome. Further investigation with larger numbers and multivariate analysis is needed to validate if a high RS serves as an independent predictor of benefit from genetic counseling and testing. Citation Format: Toltzis S, Casasanta N, Lipinski S, Marino A, McHenry A, Denduluri N, Rodriguez P, Kaltman R. Relationship between hereditary cancer syndromes and oncotype DX recurrence score [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 P1-07-21.

Abstract P4-12-11: Cost effectiveness of oncotype Dx for early stage breast cancer under National health insurance

Abstract Background : Oncotype Dx is being used increasingly for risk stratification to identify for patients with estrogen receptor-positive (ER+), node negative early-stage breast cancer who are most likely to benefit from adjuvant chemotherapy. In Korea, all citizens are covered by national health insurance (NHI), besides patients just pay 5% of hospital bill, if who diagnosed with cancer. NHI can help solve the financial burden for cancer patients. So the acquisition costs of the Oncotype DX test are sometimes a barrier to its widespread use. This study was conducted for existing cost-effectiveness analyses of Oncotype DX in Korea. Methods : We analyzed the hospital expenses of patients who diagnosis with LN-negative ER-positive early-stage breast cancer from October 2010 to October 2016 in Seoul National University Hospital. All patients are possible candidates for adjuvant chemotherapy. Among them 273 patients were tested Oncotype Dx. A cost-utility analysis (CUA) was performed. We analyzed the hospital expenses of chemotherapy by regimens who underwent adjuvant chemotherapy patients, and costs of accompanying adverse event. Each costs of therapy were derived from the hospital administration and expressed by USD. (KRW convert into USD) We also analyzed every patient charges and real expense. Result : Of 273 patients, 39(14.3%) were underwent adjuvant chemotherapy. The patients proportion by regimens are FAC(56.4%), AC(10.3%), AC followed by weekly paclitaxel (5.1%), TC(10.3%), AC followed by docetaxel (5.1%), TC and CMF etc. Each patient's hospital expense are roughly 3,000 USD (2,200 – 4,000 USD), it including all costs of laboratory test, computer tomography, chest x-ray, chemoagents and other medications. Of these costs, patients should pay only 5% so it could be around 150 USD (110-200USD). Disccusion ; The economic benefits of Oncotype DX are modelled by an overall reduction in chemotherapy usage, thus avoiding associated costs and disutility, and an increase in chemotherapy usage in the high RS group, reducing the risk of recurrence and improving health outcomes. Several studies shows Oncotype DX has been proposed to better estimate baseline risk and response to chemotherapy, to appropriately target chemotherapy to higher risk patients. In the costeffectiveness model, decision making with Oncotype DX in addition to standard decision-making tools is compared with standard decision making without Oncotype DX. From this study, most patient (234 of 273, 85.7%) who are possible candidates for adjuvant chemotherapy avoiding the treatment. A number of studies have looked at the impact of Oncotype DX on clinical decision making. But under the special environment of Korea that most costs who diagnosed with cancer covered by National Insurance health, it relatively expensive than other conturies. So it deserve much consideration that necessity of further studies and reaserches to develop new tools that could be more reasonable in cost in Korea. Citation Format: Kim Y, Han W. Cost effectiveness of oncotype Dx for early stage breast cancer under National health insurance [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 P4-12-11.

Abstract P1-06-05: Clinical practice and mortality in patients with oncotype DX intermediate score: What do we know about the gray zone?

Abstract BACKGROUND: The 21 gene expression signature Oncotype DX (ODX) is a powerful predictor of disease outcome in early stage hormone receptor positive breast cancer. ODX can be used for better risk stratification of patients who may benefit from chemotherapy. ODX testing increases confidence in treatment decisions especially when ODX recurrence score (RS) is low or high. However, for the intermediate RS, decisions on receiving chemotherapy or not is a joint decision made by the physician and patient, in part because results from the TAILORx and RxPONDER randomized clinical trials addressing this very important clinical question has yet to be published. OBJECTIVE: To examine “real world” oncology practice and survival outcome for breast cancer patients with ODX RS score in the intermediate range. METHODS: A retrospective cohort of women diagnosed with early stage, hormone receptor positive breast cancer whose ODX score was in the intermediate range was established using the National Cancer Data Base (NCDB), 2009-2013. We assessed the relationship of overall survival with chemotherapy receipt and RS score using Cox proportional hazards models adjusted for patient characteristics, including age, race/ethnicity, grade, year of diagnosis, Charlson Co-morbidity Index, lymphovascular invasion, nodal involvement, tumor size, and histology. Intermediate RS score was analyzed as both continuous variable and categorical variables (18-20, 21-23, 24-26, and 27-30). RESULTS: Of 24,945 females reported to have intermediate ODX score, 10,179 (41.4%) received chemotherapy. Receipt of chemotherapy depended on ODX score monotonically, ranging from 19.1% in patients with RS = 19 to 76.1% in patients with RS = 30. In total, 426 patients have died from all causes. Overall, chemotherapy receipt was associated with a statistically significant reduction in the risk of death (hazard ratio=0.77; 95% confidence interval [CI]: 0.62-0.96, p=0.02) in multivariable Cox model. RS score was statistically positively associated with increased risk of death, with one unit increment in RS corresponding to 6.2% increased mortality risk (95% CI 3.2%- 9.2%, p&amp;lt;0.0001). Using a categorical scale, we found patients with intermediate ODX scores in RS 27-30 range had 1.64-fold increased risk of death (95% CI: 1.13-2.37) compared to patients with ODX scores in RS 18-20 range.. The association between ODX score and overall survival was more pronounced in women younger than 50 (hazard ratio per 1 unit increment = 1.28, 95% CI: 1.17-1.40) than in women 50 years or older (hazard ratio per 1 unit increment = 1.04, 95% CI: 1.01-1.07). CONCLUSION: Our analysis revealed the ODX score in the intermediate range still has prognostic value for overall survival especially for young-onset breast cancer patients, which is independent of other clinopathologic factors. As we eagerly await results from randomized clinical trials, young women with intermediate RS should be counseled to consider more aggressive treatment including chemotherapy, ovarian function suppression or participation in ongoing clinical trials of CDK inhibitors to improve overall survival outcomes. Citation Format: Ibraheem AF, Press D, Dezheng H, Olopade F. Clinical practice and mortality in patients with oncotype DX intermediate score: What do we know about the gray zone? [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 P1-06-05.

A study of association of Oncotype DX recurrence score with DCE-MRI characteristics using multivariate machine learning models.

To determine whether multivariate machine learning models of algorithmically assessed magnetic resonance imaging (MRI) features from breast cancer patients are associated with Oncotype DX (ODX) test recurrence scores. A set of 261 female patients with invasive breast cancer, pre-operative dynamic contrast enhanced magnetic resonance (DCE-MR) images and available ODX score at our institution was identified. A computer algorithm extracted a comprehensive set of 529 features from the DCE-MR images of these patients. The set of patients was divided into a training set and a test set. Using the training set we developed two machine learning-based models to discriminate (1) high ODX scores from intermediate and low ODX scores, and (2) high and intermediate ODX scores from low ODX scores. The performance of these models was evaluated on the independent test set. High against low and intermediate ODX scores were predicted by the multivariate model with AUC 0.77 (95% CI 0.56-0.98, p < 0.003). Low against intermediate and high ODX score was predicted with AUC 0.51 (95% CI 0.41-0.61, p = 0.75). A moderate association between imaging and ODX score was identified. The evaluated models currently do not warrant replacement of ODX with imaging alone.

Cost Effectiveness of Gene Expression Profile Testing in Community Practice.

Purpose Gene expression profile (GEP) testing can support chemotherapy decision making for patients with early-stage, estrogen receptor-positive, human epidermal growth factor 2-negative breast cancers. This study evaluated the cost effectiveness of one GEP test, Onco type DX (Genomic Health, Redwood City, CA), in community practice with test-eligible patients age 40 to 79 years. Methods A simulation model compared 25-year societal incremental costs and quality-adjusted life-years (QALYs) of community Onco type DX use from 2005 to 2012 versus usual care in the pretesting era (2000 to 2004). Inputs included Onco type DX and chemotherapy data from an integrated health care system and national and published data on Onco type DX accuracy, chemotherapy effectiveness, utilities, survival and recurrence, and Medicare and patient costs. Sensitivity analyses varied individual parameters; results were also estimated for ideal conditions (ie, 100% testing and adherence to test-suggested treatment, perfect test accuracy, considering test effects on reassurance or worry, and lowest costs). Results Twenty-four percent of test-eligible patients had Onco type DX testing. Testing was higher in younger patients and patients with stage I disease ( v stage IIA), and 75.3% and 10.2% of patients with high and low recurrence risk scores received chemotherapy, respectively. The cost-effectiveness ratio for testing ( v usual care) was $188,125 per QALY. Considering test effects on worry versus reassurance decreased the cost-effectiveness ratio to $58,431 per QALY. With perfect test accuracy, the cost-effectiveness ratio was $28,947 per QALY, and under ideal conditions, it was $39,496 per QALY. Conclusion GEP testing is likely to have a high cost-effectiveness ratio on the basis of community practice patterns. However, realistic variations in assumptions about key variables could result in GEP testing having cost-effectiveness ratios in the range of other accepted interventions. The differences in cost-effectiveness ratios on the basis of community versus ideal conditions underscore the importance of considering real-world implementation when assessing the new technology.

The use of automated Ki67 analysis to predict Oncotype DX risk-of-recurrence categories in early-stage breast cancer.

Ki67 is a commonly used marker of cancer cell proliferation, and has significant prognostic value in breast cancer. In spite of its clinical importance, assessment of Ki67 remains a challenge, as current manual scoring methods have high inter- and intra-user variability. A major reason for this variability is selection bias, in that different observers will score different regions of the same tumor. Here, we developed an automated Ki67 scoring method that eliminates selection bias, by using whole-slide analysis to identify and score the tumor regions with the highest proliferative rates. The Ki67 indices calculated using this method were highly concordant with manual scoring by a pathologist (Pearson’s r = 0.909) and between users (Pearson’s r = 0.984). We assessed the clinical validity of this method by scoring Ki67 from 328 whole-slide sections of resected early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. All patients had Oncotype DX testing performed (Genomic Health) and available Recurrence Scores. High Ki67 indices correlated significantly with several clinico-pathological correlates, including higher tumor grade (1 versus 3, P<0.001), higher mitotic score (1 versus 3, P<0.001), and lower Allred scores for estrogen and progesterone receptors (P = 0.002, 0.008). High Ki67 indices were also significantly correlated with higher Oncotype DX risk-of-recurrence group (low versus high, P<0.001). Ki67 index was the major contributor to a machine learning model which, when trained solely on clinico-pathological data and Ki67 scores, identified Oncotype DX high- and low-risk patients with 97% accuracy, 98% sensitivity and 80% specificity. Automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy, in a manner that integrates readily into the workflow of a pathology laboratory. Furthermore, automated Ki67 scores contribute significantly to models that predict risk of recurrence in breast cancer.