High Oncotype DX Recurrence Score Research Articles

Identifying High Recurrence Risk in Breast Carcinoma Patients Through Spatial Transcriptomic Analysis.

Comparing gene expression profiles according to recurrence risk using spatially resolved transcriptomic analysis has not been reported. This study aimed to identify distinct genetic features of breast carcinoma associated with a high Oncotype DX Recurrence Score (ORS). Patients were categorized into two groups, ORS-high (ORS-H; two patients) and ORS-non-high (ORS-NH; five patients). We performed digital spatial profiling and bioinformatic analyses to investigate the spatial transcriptomic profiles. Lysozyme (LYZ), complement C1q C chain (C1QC), and complement C1q B chain (C1QB) exhibited the highest fold changes in the stromal compartment of the ORS-H group. Gene ontology enrichment analysis of the ORS-H group revealed significant up-regulation of genes associated with immune response in the stromal compartment, including lymphocyte-mediated immunity, adaptive immune response related to the immunoglobulin superfamily, and leukocyte-mediated immunity. Gene set enrichment analysis showed significant positive enrichment of gene sets associated with interferon (IFN) response and complement pathways in the stromal compartment. This study highlights significant differences in gene expression profiles and spatially resolved transcriptional activities between ORS-H and ORS-NH breast carcinomas. The significant up-regulation of genes and pathways associated with cell-mediated immunity, IFN response, and complement C1q in the stromal compartment of the ORS-H group warrants further evaluation with larger population cohorts.

Factors associated with benefit of adjuvant chemotherapy in patients with T1b/T1c HR-positive/HER2-negative breast cancer and high multigene recurrence score.

e12540 Background: Patients diagnosed with early-stage HR-positive/HER2-negative Breast Cancer (BC) and high Oncotype DX Recurrence Score (RS ≥26) are offered adjuvant chemotherapy and endocrine therapy compared (CET) to endocrine therapy alone (ET). We sought to investigate if additional clinical factors that could further determine benefit from chemotherapy in patients with T1b/T1c and N0 tumors with high Oncotype DX to help deescalate treatment by avoiding chemotherapy induced toxicity. Methods: The purpose of this study is to determine the clinical factors associated with a survival difference from CET compared to ET alone in T1b/T1c and N0 BC. We analyzed the record of patients diagnosed with T1b/T1cN0M0 HR-positive/HER2-negativeBC and RS ≥26 between 2006 and 2020 from the National Cancer Database. Patients were separated into two groups based on their treatment: CET or ET and the following characteristics were assessed: age, grade, histology, and RS (26-30, 31-40, 41-100) to determine overall survival differences among the two groups. Chi-square was performed to evaluate the association between baseline categorical characteristic variable and chemotherapy treatment. Survival analysis of treatment modalities using Kaplan Meier curves and univariate Cox regression. Multivariate Cox regression with backwards elimination was performed for subgroup analyses. Results: A total of N=19,373 eligible patients were identified, n=14,422 (74.4%) received CET and the rest ET alone. The mean age at diagnosis was 59.6 years (SD=10.3); 86.6% presented with invasive ductal carcinoma and 83.3% had a Charlson-Deyo Comorbidity Score of 0. In the overall group, patients who received CET had a higher median overall survival than endocrine therapy alone (65.7 versus 52.1 months, log-rank p-value<.0001). However, further analysis noted that treatment with CET showed better outcome compared to ET alone in the following subgroups of patients: invasive ductal histology (95% OS 65.5 versus 52.7 months, log-rank p-value<.0001) and RS >30 (95% OS 63.6 versus 40.5 months, log-rank p-value<.0001). Importantly, multivariable cox regression subgroup analysis revealed no significant overall survival difference among the subgroup of patients with T1b/T1c and low grade (p=0.286) or RS 26-30 (p=0.200) with CET compared to ET alone. Conclusions: This large database confirms the heterogeneity of BC in patients with low burden disease despite high Oncotype.While patients diagnosed with T1b/T1cN0M0 and high RS (>30) could benefit from CET compared to ET alone as per standard practice, additional criteria could be considered in this group including low grade or RS 26-30 to better determine which population of patients do not benefit from the addition of chemotherapy and accordingly individualized chemotherapy decision might be made to minimize toxicity.

The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Correlation ofKi-67 proliferative index with oncotype DX recurrence score in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer with low-burden axillary nodal disease - areview of137 cases.

Theuse ofchemotherapy in breast cancer management has significantly contributed to thedecrease in its mortality. Currently, theprognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, theincreasing use ofadvanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided theability to estimate therisk ofrecurrence. Research has demonstrated that theODX-RS helps to predict recurrence risk and thepotential benefit ofchemotherapy in breast cancer. As aresult, it can assist clinicians in making decisions regarding using thechemotherapy. Thegoal ofwork is to explore thecorrelation between theODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In thehigh Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, theresults show no significant correlation between theODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).

Probability of a high recurrence score for breast cancer on the Oncotype DX test in males: a case series

Abstract Introduction: Male breast cancer (MBC) is a rare disease that accounts for 1% of breast cancers. The Oncotype DX test (a genomic signature that assesses the expression of 21 genes to estimate the recurrence score [RS]) has been widely used in MBC to select patients for adjuvant chemotherapy. Objective: To describe 5 cases of MBC in which a nomogram was used to predict the probability of having a high Oncotype DX score for breast cancer and the need to perform genomic signature. Materials and methods: Case series study in which five patients with MBC treated between 2007 and 2020 at a cancer institution in Teresina (Brazil) were included. A nomogram was performed to evaluate five clinical and pathological variables (age, body size, tumor size, grade, recurrence score status, and histologic type of carcinoma). Case series: The mean age of the patients at diagnosis was 69 years (mean tumor size: 2.6cm). All patients received hormone therapy with tamoxifen, three received chemotherapy, and one received radiation therapy after breast surgery (mastectomy). During a median follow-up period of 88 months, one case had a recurrence (bone metastasis). Based on the nomogram results, two patients had a high probability of a high RS (36% and 45%) and only one patient (case 3) underwent Oncotype DX testing (RS: 20). Conclusions: In the present series of five cases, based on the nomogram results, only two patients (cases 3 and 4) had a high probability of a high Oncotype DX recurrence score; however, due to financial constraints, this test was only performed on one of these two patients. The patient who underwent the test (case 3) did not receive adjuvant chemotherapy and remained alive with bone metastases until the end of the follow-up period. Conversely, the patient who could not undergo the examination (case 4) received adjuvant chemotherapy and was alive without any signs of disease.

252P Adjuvant chemotherapy in T1a/bN0 breast cancer patients with high oncotype DX recurrence scores (RS>25)

252P Adjuvant chemotherapy in T1a/bN0 breast cancer patients with high oncotype DX recurrence scores (RS>25)

Evaluation of multigene assays as predictors for response to neoadjuvant chemotherapy in early-stage breast cancer patients

OncotypeDX and MammaPrint assays have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in early-stage breast cancer patients. We analyzed the 2010–2019 National Cancer Database and found that high OncotypeDX recurrence scores or high MammaPrint scores were associated with greater odds of pCR. Our findings suggest that OncotypeDX and MammaPrint testing predict pCR after NACT and could facilitate clinical decision-making between clinicians and patients.

ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer

Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 ≥10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC.

The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer

An effect of non-oncology medications on cancer outcome has been proposed. In this study, we aimed to systematically examine the impact of commonly prescribed non-oncology drugs on clinical risk and on the genomic risk [based on the Oncotype DX recurrence score (RS)] in early breast cancer (BC). We collected data on clinical risk (stage and grade), genomic risk (Oncotype DX RS), and on non-oncology medications administered to 1423 patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative BC during the month of their surgery. The influence of various medications on clinical and genomic risks was evaluated by statistical analysis. Out of the multiple drugs we examined, levothyroxine was significantly associated with a high Oncotype DX RS (mean 24.78; P < 0.0001) and metformin with a low Oncotype DX RS (mean 14.87; P < 0.01) compared with patients not receiving other non-oncology drugs (mean 18.7). By contrast, there were no differences in the clinical risk between patients receiving metformin, levothyroxine, or no other non-oncology drugs. Notably, there was no association between the consumption of levothyroxine and metformin and proliferation marker (Ki67) levels, but both drugs were significantly associated with progesterone-related features, suggesting that they influence genomic risk through estrogen-dependent signaling. The results of this study indicate a significant impact of metformin and levothyroxine on clinical decisions in luminal BC, with potential impact on the clinical course of these patients.

The Oncotype DX Recurrence Score's Impact on the Management of Oestrogen-Positive/Human Epidermal Growth Factor Receptor 2-Negative, Low-Burden Axillary Status Breast Cancer (REHAB Study): Results of a Single Centre.

BackgroundThe Oncotype DX Recurrence Score (ODX-RS) is increasingly utilized in oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, low-burden axillary disease early operable breast cancer. It has been demonstrated to predict the benefits of adjuvant chemotherapy, hence supporting individualized decisions on adjuvant therapy.AimTo investigate the application of ODX-RS as an adjuvant treatment decision tool in breast cancer operated in our unit.MethodsA total of 107 eligible patients who were operated on between 2017 and 2021 in Basildon University Hospital, UK were enrolled in this study. In this retrospective study, the clinical data, including patient’s age, tumour size, ER status, HER2 status, Ki67 proliferative index (Ki67-PI), nodal status, tumour grade, and ODX-RS, were collected. In the study design, the oncologist had the opportunity to assess the need for adjuvant chemotherapy for patients with ER-positive, HER2-negative, low-burden axillary lymph node disease, early breast cancer by using tumour characteristics and the PREDICT tool without knowing the ODX-RS results. The clinician's decision was matched against the breast multidisciplinary team's recommendations after ODX-RS utilisation, and the results were explored.ResultsThe median ODX-RS of cohort tumours was 18 in the age group > 50 years, with ODX-RS ≥ 26 found in 18% of the group (n = 12). In the age group ≤ 50 years, 17% (n = 7) had ODX-RS between 21 and 25 and only 7% (n = 3) had ODX-RS ≥ 26. Without using ODX-RS, only 16% of the patients had been offered adjuvant chemotherapy in addition to the hormonal manipulation therapy; however, after using ODX-RS, up to 33% of the cohort was suitable for adjuvant chemotherapy in addition to the hormonal manipulation therapy. The changes in the recommendations after ODX-RS utilisation have been noticed in 29% of the cohort.ConclusionThis study revealed that ODX-RS supported decision-making regarding postoperative adjuvant chemotherapy, especially when other tumour biomarkers, such as tumour size, grading, or Ki-67, indicated lower risk criteria. Patients with a high ODX-RS were offered chemotherapy where appropriate and its use led to a 15% rate of initial decision change in adjuvant treatment decisions; this involved either recommending chemotherapy or its omission.

Comparison of predicted benefit using RS clin versus observed benefit in a U.S. registry of stage I ER-positive HER2-negative high oncotype DX RS breast cancer.

544 Background: The 21-gene recurrence score assesses the risk of distant breast cancer recurrence and predicts the benefit of adjuvant chemotherapy in ER positive early-stage breast cancer. However, clinicopathologic risk factors continue to impact absolute benefit of adjuvant chemotherapy. Absolute benefit of adjuvant chemotherapy in low clinicopathologic risk Stage I ER positive breast cancer with high Oncotype RS is an important clinical component of shared decision making. The RSClin clinical tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was found to be more prognostic than RS result alone. We assessed RS Clin predicted benefit and compared to absolute benefit in low clinicopathologic risk Stage I ER positive breast cancer with high Oncotype RS as observed in the NCDB. Methods: Using the National Cancer Data Base (NCDB), we identified female patients age 18-75, ER positive and Her 2 negative, 21 gene signature high risk &gt; 25 with negatives surgical margins, &lt;2cm, lymph node negative breast cancers, who had received endocrine therapy with either Tam or AI diagnosed during 2010 - 2017. Clinicopathologic factors and RS were entered into the RSClin calculator, and a predicted benefit of chemotherapy was calculated for each patient. Using NCDB data, Cox proportional hazards regression models were used to project absolute survival benefit at 10 years from diagnosis for those who did vs those who did not receive chemotherapy. NCDB-derived absolute benefit of chemotherapy was compared to estimated absolute benefit as predicted by the RSClin tool. Results: 18,226 patients were identified. Stages T1a = 670(4%), T1b = 4,289(23%), and T1c = 13,267(73%). Median age 59 years (21-75). Race white 84% (15,365), black 10% (1840), and other 1021(6%). AI use 80% (14,711) was greater than Tam use 20% (3515). Chemotherapy was administered in 75% (13,827) of patients. Most patients had high or intermediate grade disease, G3 45% (8225), G2 46% (8328), and G1 9% (1672). Median duration of follow up was 57 months (2-160). Probability of death T1b at 10yrs with chemotherapy was 8.5%, and without chemotherapy was 15.1% with an absolute benefit of 6.6%. Predicted benefit in T1b using RS Clin at 10yrs was 10.8%. Probability of death for T1c at 10yrs with chemotherapy was 15.1%, and without chemotherapy was 23.5% with an absolute benefit of 8.4%. Predicted benefit in T1c using RS Clin at 10yrs was 14%. Conclusions: Patients with stage IB and IC hormone receptor positive HER2 negative breast cancers with high RS had a lower absolute benefit than predicted by RS Clin. The RSClin tool overestimated benefit of therapy in both IB and IC stages requiring caution when using this tool in patients with the lowest clinicopathologic risks.

Clinical Utility of Multigene Profiling Assays in Early-Stage Invasive Breast Cancer: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline.

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors.

The impact of age and nodal status on variations in oncotype DX testing and adjuvant treatment

Oncotype DX (ODX) recurrence score (RS) is a validated tool to guide the use of adjuvant chemotherapy (AC) in hormone receptor+/HER2- breast cancer. In this analysis, we examine (1) characteristics associated with ODX testing and (2) the association between ODX RS and receipt of AC across age and nodal status. Women with HR+/HER2–, early-stage (T1-2, N0-1) breast cancers from 2010–2017 in the National Cancer Database were included. 530,125 met inclusion and 255,971 received ODX testing. Older women were less likely to receive testing; however, nodal positivity increased use of testing. High ODX RS was associated with increased mortality, though the association was not consistent across age and was most strongly associated with mortality among younger, node-negative women. Older women with high ODX RS, regardless of nodal status, were less likely to receive AC. Clinicians may be employing ODX RS to support treatment decisions against the receipt of AC.

Correlation of circulating or disseminated tumor cells with the Oncotype DX Recurrence Score.

New biomarkers are emerging to predict recurrence risk in women with early-stage breast cancer. High Oncotype DX Recurrence Score® (RS) is associated with worse disease-free and overall survival. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in breast cancer. We investigated the association between high RS and CTCs or DTCs. Using a prospective database, we evaluated patients with hormone receptor-positive/HER2-negative, node-negative invasive breast cancer from 1/2005 to 1/2017. RS was classified using TAILORx study cutoff points: low (< 11), intermediate (11-25), and high (> 25). CTCs were assessed using CellSearch® and DTCs using cytospin specimens of bone marrow aspirates. Positive result was defined as one or more CTCs or DTCs identified. Chi-square analyses were utilized to evaluate the relationship between RS and CTCs or DTCs. 233 patients were identified from a prospective database, of which 96 had RS results. Of these patients, 88 had CTC results and 58 had DTC results. CTCs were detected in 17/88 (19%) patients, while DTCs were detected in 20/58 (34%). Patients with high RS were not more likely to have CTCs (18%) compared to patients with low/intermediate RS (20%; p = 0.919). Similarly, high RS was not associated with DTC detection, with DTCs present in 40% of patients with high RS versus 33% with low/intermediate RS (p = 0.687). In the subgroup of patients ≤ 50years, no associations were found between high RS and CTCs (p = 0.383) or DTCs (p = 0.234). High Oncotype DX RS did not correlate with CTCs in blood or DTCs in bone marrow in our study.

Breast-Conserving Therapy Including Whole-Breast Irradiation is Associated with Better Overall Survival Compared to Mastectomy Alone in Patients with Early-Stage, Lymph Node-Negative Breast Cancer with High OncotypeDX Recurrence Score: an NCDB Analysis

Previous single-institutional retrospective studies suggest improved overall survival (OS) in women with early stage, lymph node negative breast cancer treated with breast conserving therapy including whole breast irradiation (BCT), compared to those treated with mastectomy alone. In this study, we compared OS between these two cohorts using the NCDB. Additionally, we examined OS after stratifying by OncotypeDX recurrence score. We performed a retrospective cohort analysis of NCDB patients with non-metastatic, pT1-2, pN0 breast cancer treated between 2006 and 2014. Patients were classified into two categories: those undergoing BCT (breast conserving surgery followed by whole breast irradiation), and those undergoing mastectomy without post-mastectomy irradiation. Patients were matched using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights. Patients were matched for race, age, grade, pT stage, LVI, receptor status, hormone therapy, chemotherapy, OncotypeDX recurrence score, comorbidity score, year of diagnosis, treatment facility type, insurance status, median income, US region, laterality, and tumor quadrant. The primary objective was to compare OS between BCT and mastectomy patients. After IPTW-matching, the analysis included 149,273 and 87,073 patients undergoing BCT and mastectomy, respectively. There were no differences between the matched groups in any of the included variables after matching. Median follow up for the matched cohorts were 48.5 (BCT) and 47.3 months (mastectomy). OS was better in the BCT group at 5 years (94% vs 92%, P<0.0001) and 7 years (81.1% vs 73.3%, P<0.0001). In univariate Kaplan-Meier (UV) and multivariate cox proportional hazard analyses (MVA), treatment with BCT was a positive predictor of OS with a mastectomy HR of 1.4 in MVA (95% CI 1.3-1.4, P=0.0001), when setting BCT as reference. We then stratified patients by OncotypeDX RS into low RS (≤25), 36, 571 patients with BCT and 17,785 with mastectomy, or high RS (>25), 7,018 patients with BCT and 3,811 patients with mastectomy. Median follow up for patients with available RS were 42.3 months (BCT) and 41.6 months (mastectomy). OS was not different for patients undergoing BCT or mastectomy in the low RS cohort at 5 or 7 years (P=0.339 and 0.289). For those with high RS, OS was better in the BCT group at 5 years (95% vs 93%, P=0.001) and 7 years (93% vs 88%, P=0.0001). In MVA, treatment with BCT was a positive predictor of OS with a mastectomy HR of 1.5 (95% CI 1.2-1.9, P<0.0001), when setting BCT as reference. Our analysis suggests that BCT is associated with better OS compared to mastectomy alone in patients with early stage, lymph node negative breast cancer with a high OncotypeDX recurrence score. We hypothesize that incidental irradiation to regional lymphatics, may underly the improvement in OS with BCT in this high-risk cohort. Further investigation into patterns of failure in these patient cohorts is needed.

Abstract P2-07-11: Prediction of the Oncotype Dx recurrence score (RS) from clinicopathologic factors

Abstract Background: The Oncotype Dx assay is currently used as an aid to therapeutic decisions for the adjuvant treatment of women with ER-positive, Her2-negative, lymph node-negative or -micrometastatic breast cancer. The recently reported TAILORx study showed that no or minimal benefit is derived from adjuvant chemotherapy in patients with an Oncotype Dx Recurrence Score (RS) of 25 or less. Methods: Charts of breast cancer patients that had the Oncotype Dx test in our cancer center in a nine-year period were reviewed. Data on demographic, and cancer-specific characteristics of the included patients were extracted. Predicted disease recurrence from the Oncotype Dx test was recorded and correlated with select clinicopathologic characteristics. Results: Two hundred and thirty patients with ER-positive, Her2-negative, lymph node-negative or micrometastatic breast cancer were included. Mean age was 65 years-old (SD 9.9). Two hundred and three patients (88.3%) were post-menopausal and one hundred and thirty-three patients (57.8%) were 65 years-old or older. Two hundred and nine patients (90.9%) had lymph node-negative disease. Oncotype Dx recurrence score was low (&amp;lt;11) in sixty-four patients (27.8%), intermediate (11-25) in one hundred and forty patients (60.9%) and high (&amp;gt;25) in twenty-six patients (11.3%). High tumor grade and low progesterone receptor (PR) staining by IHC were the two clinicopathologic factors most associated with a high Oncotype Dx RS (x2 test p &amp;lt;0.00001 and Fisher's exact test p &amp;lt;0.0001). A predictive index (PI) was constructed, assigning one point each for grade 3 and PR staining in 20% or less of tumor cells. A PI of 0 was observed in one hundred and thirty-eight patients (60%), a PI of 1 was observed in seventy-one patients (30.9%), and a PI of 2 was observed in twenty-one patients (9.1%). One hundred and thirty-four patients (97.1%) with a PI of 0 had a RS of 25 or less. Patients with a PI of 1 and 2 had a RS of &amp;gt;25 in 12.7% and 61.9% of cases, respectively. Conclusion: The PI based on tumor grade and PR we propose is a simple predictor of Oncotype Dx RS. 97.1% of patients with a grade 1 or 2 tumor and PR positivity in &amp;gt;20% of tumor cells had a RS of 25 or less. The Oncotype Dx test and its associated cost can therefore be avoided in these patients, especially in low-resource settings. Citation Format: Voutsadakis IA, Thibodeau S, Reed M. Prediction of the Oncotype Dx recurrence score (RS) from clinicopathologic factors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-11.

Abstract P3-01-06: Correlation of disseminated or circulating tumor cells with the OncotypeDX recurrence score

Abstract Background: New biomarkers continue to emerge to predict the risk of recurrence in women with early stage breast cancer. A high OncotypeDX Recurrence Score (RS)® has been found to be associated with worse disease-free and overall survival in patients with early stage breast cancer. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in patients with breast cancer. We sought to evaluate the association between high RS and CTCs and DTCs. Methods: We evaluated patients with hormone receptor positive, HER2 negative, node-negative invasive breast cancer from a prospective database from 1/2005 to 1/2017. RS was classified based on the new TAILORx study cutoff points as low (&amp;lt;11), intermediate (11-25), and high (&amp;gt;25). CTCs were assessed using CellSearch. For DTCs cytospin specimens of bone marrow aspirates, enriched for epithelial cells by density gradient separation, were immunostained using a pancytokeratin cocktail of antibodies, including AE1/AE3, CAM5.2, MNF116, cytokeratin 8 (CK8), and CK18. CTCs and DTCs were considered to be positive if one or more CTCs or DTCs were identified, respectively. Chi square analyses were utilized to evaluate for a relationship between OncotypeDX RS and CTCs or DTCs. Statistical analyses were performed in SPSS version 24 with p value &amp;lt;0.05 considered significant. Results: Two hundred and thirty patients meeting the above criteria were identified from a prospective database, of which 106 had OncotypeDX testing results. Of the patients with available OncotypeDX data, 93 patients had CTC results and 60 patients had DTC results. CTCs were detected in the blood of 18/93 (19.4%) patients, while DTCs were detected in the bone marrow of 20/60 (33.3%) patients. Patients with high RS were not more likely to have CTCs as compared with patients who had low or intermediate RS (16.7% vs 19.8%, p=0.801). Similarly, high RS was not associated with the detection of DTCs, with DTCs present in 44.4% of patients with high RS, compared with 31.4% of patients with low or intermediate RS (p=0.443). In the subgroup of patients ≤50 years of age no associations were found between high RS and CTCs (p=0.720) or DTCs (p=0.151). Conclusions: High OncotypeDX RS did not correlate with CTCs in the blood or DTCs in the bone marrow in our study. Citation Format: Tevis SE, Hall C, Meas S, Hwang R, Lucci A. Correlation of disseminated or circulating tumor cells with the OncotypeDX recurrence score [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-06.

Oncotype DX® Recurrence Score as a Predictor of Response to Neoadjuvant Chemotherapy.

The Oncotype DX® assay has been validated in predicting response to adjuvant chemotherapy in breast cancer. Its role in neoadjuvant chemotherapy (NCT) has not been established. The National Cancer Database was used to identify all patients with T1-T3, ER-positive, HER2-negative primary invasive breast cancer diagnosed from 2010 to 2015 who had Oncotype DX recurrence scores (RS) and received NCT. RS were classified as low, intermediate, or high. Unadjusted and adjusted regression analyses were performed to determine the association between pathologic complete response (pCR) and RS. A total of 989 patients (mean age, 54.6years) with available RS who underwent NCT were identified. RS were low in 227 (23.0%) patients, intermediate in 450 (45.5%) patients, and high in 312 (31.5%) patients. Most patients had a T1 (431 [43.6%]) or T2 tumor (451 [45.6%]). Most had N0 disease (757 [76.5%]). Tumor grades were 1 (123 [12.4%]), 2 (517 [52.3%]), or 3 (349 [35.3%]). pCR was achieved by 42 (4.3%) patients. Adjusted multivariable analysis showed a significant association between pCR and high RS (odds ratio 4.87; 95% confidence interval 2.01-11.82). High Oncotype DX RS was associated with pCR after NCT in this national cohort of ER-positive, HER2-negative patients. Oncotype DX testing could help to identify patients most suited for NCT and should be considered for incorporation into the multidisciplinary decision-making process.

Clinical Utility of Multigene Profiling Assays in Early-Stage Breast Cancer

This clinical practice guideline was developed to determine the level of evidence supporting the clinical utility of commercially available multigene profiling assays and to provide guidance about whether certain breast cancer patient populations in Ontario would benefit from alternative tests in addition to Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.). A systematic electronic Ovid search of the medline and embase databases sought out systematic reviews and primary literature. A systematic review and practice guideline was written by a working group and was then reviewed and approved by Cancer Care Ontario's Molecular Oncology Advisory Committee. Twenty-four studies assessing the clinical utility of Oncotype dx, Prosigna (NanoString Technologies, Seattle, WA, U.S.A.), EndoPredict (Myriad Genetics, Salt Lake City, U.S.A.), and MammaPrint (Agendia, Irvine, CA, U.S.A.) were included in the evidence base. The clinical utility of multigene profiling assays is currently established for an appropriate subset of patients with estrogen receptor-positive, her2-negative, node-negative breast cancer for whom a decision to give chemotherapy is difficult to make. For patients with estrogen receptor-positive tumours who receive tamoxifen alone, Oncotype dx, Prosigna, and EndoPredict validly identify a low-risk population with favourable outcomes, indicating that a low-risk assay result is actionable and the decision to withhold chemotherapy is supported. Clinical evidence indicates that a high Oncotype dx recurrence score can predict for chemotherapy benefit, but a high Prosigna or EndoPredict score, although prognostic, is not, based on clinical trial evidence, directly actionable. Prosigna and EndoPredict are statistically more likely to identify a population at risk for recurrence beyond 5 years, but that information is currently not actionable because of a lack of interventional studies.

Comparison of Oncotype DX Recurrence Score by Histologic Types of Breast Carcinoma.

Oncotype DX (ODX) is a widely used commercial assay that estimates the risk of distant recurrence and may predict the benefit of chemotherapy in a subset of breast cancers. Some studies have shown the ability to predict Oncotype DX recurrence score (ODXRS), based on routinely reported pathologic features; however, there are limited data correlating specific histologic type of breast cancer to ODXRS. To compare ODXRS to specific histologic types of breast cancer. One hundred eighty-four cases were sent for ODXRS testing and the results were compared with histologic type and grade. The highest average ODXRS was seen in invasive ductal carcinoma with micropapillary features (29) followed by invasive ductal carcinoma not otherwise specified (mean = 19.4, SD = 11.6), invasive mucinous carcinoma (mean = 17.2, SD = 5.9), invasive lobular carcinoma (mean = 15.7, SD = 7.2), mixed ductal and lobular carcinoma (mean = 14.1, SD = 7.7), tubular carcinoma (10.0), and mixed ductal and mucinous carcinoma (mean = 8.0, SD = 4.2). Most tumors that had a high ODXRS were grade 3 invasive ductal carcinoma, representing 13 of a total of 20 cases (65%). Interestingly, 3 of the 4 cases of pure invasive mucinous carcinoma had an intermediate ODXRS. Although the numbers are small, our findings raise further awareness of the significance between histologic type and grade, and RS in breast cancer. In some special histologic types of breast cancer, particularly those considered to follow either an excellent or poor clinical course by histology alone, it is unclear whether the ODXRS results are as meaningful as in carcinomas of no special type. Further investigation with higher numbers and outcome data is needed.