High Oncotype DX Research Articles

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.

Abstract P1-13-06: The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer

Abstract Intro: The Oncotype DX breast recurrence score provides newly diagnosed patients with low-risk ER/PR+ invasive breast cancer with an estimation of their 10-year risk of distant recurrence if compliant with five years of endocrine therapy. Despite the well-established benefits of endocrine therapy, to include a decrease in local and distant disease recurrence, many patients will discontinue endocrine therapy prior to five years, defined as non-persistence. We hypothesized that the individual perception of risk of recurrence conveyed by the Oncotype DX breast recurrence score directly influences persistence with endocrine therapy and patients with higher Oncotype DX breast recurrence scores may have higher rates of persistence when compared to a similar cohort with lower recurrence scores. Further, we hypothesized that disease recurrence in women with low-risk (defined as less than 26) ER/PR+ breast cancer is due primarily to non-persistence with endocrine therapy. Methods: Our study included 198 patients with low-risk ER/PR+ breast cancer treated at a comprehensive cancer center between April 2011 and April 2014 with sufficient-follow-up data of at least 5 years. Persistence was determined by chart review and defined as a minimum duration of 55 months on endocrine therapy. Multivariable ANOVA and Fisher Chi Square Exact test were used to compare the recurrence score, 10-year risk of distant recurrence, and rates of recurrence between persistent vs non-persistent patients. Results: The average recurrence score of our cohort was 14.74 with an average 10-year risk of distant recurrence of 9.8 percent with five years of endocrine therapy. The average recurrence score was 15.24 in the persistent group vs. 13.18 for the non-persistent group (p=0.029). The average 10-year risk of distance recurrence was 10.1% in persistent patients vs 9% in non-persistent patients (p=0.019). The recurrence rate (both local and distant) was 4% in persistent patients vs 16% in non-persistent patients at 5- year follow (P=<0.01). Discussion: Non-persistence to endocrine therapy represents a major unmet need in breast cancer care. The Oncotype DX breast recurrence score significantly influences persistence to endocrine therapy as our retrospective review demonstrated that patients with low-risk ER/PR+ locally invasive breast cancer with higher Oncotype DX scores are more likely to complete the recommended 5-years of endocrine therapy. Further, despite having a lower average Oncotype DX score overall, the non-persistent group had a higher rate of recurrence when compared to the persistent group. This finding further substantiates the overall effectiveness of endocrine therapy in reducing the risk of future recurrence in patients with low-risk ER/PR+ breast cancer. Mindful framing of Oncotype DX test results by providers represents a potential avenue to increase persistence through the modulation of individual risk perception and may ultimately lead to decreased rates of disease recurrence in patients with low-risk ER/PR+ invasive breast cancer. Citation Format: Jonathan Pirruccello, Elaine Kuhn, Mary Chamberlin. The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-06.

Abstract P1-02-12: Genomic testing on breast cancer core biopsy material is feasible and provides useful treatment information

Abstract Background: Genomic profiling assays for invasive breast cancer provide useful predictive and prognostic information and are performed most commonly on surgical resection specimens. Obtaining the molecular profile at the time of initial core needle biopsy is ideal because it could provide information that could significantly alter preoperative decision-making and avoid unnecessary treatments. In January 2020, the breast center began a 3 month pilot program that would reflexively send core biopsy material on all newly diagnosed patients for genomic testing using the MammaPrint (MPT) and BluePrint (BPT) assays regardless of receptor status. The goals were to determine feasibility and examine the impact to patient care. Methods: Breast core biopsy tissue was triaged by an attending pathologist as soon as slides were available. If invasive carcinoma with at least 3 mm in linear extent of tumor with 20% cellularity was identified, materials were immediately sent to Agendia for MPT/BPT testing even before ER/PR/HER2 testing was available to the pathologist. Clinicopathologic information, turn-around time (TAT) and adequacy data were tracked. The impact was discussed regularly at breast tumor board to determine if the results led to altered decision-making that could reduce unnecessary interventions and time to initial treatment. Results: 445 core biopsy specimens were sent for genomic testing. Of those 442, (97%) yielded genomic results with an average TAT from biopsy to genomic result of 11 calendar days. MPT identified 233 (53%) cases that were low risk and 209 (47%) cases that were high risk. BPT showed that 60 (14%) cases were Basal, 18 (4%) cases were HER2, and 364 (82%) cases were Luminal. Further analysis of the Luminal subgroup demonstrated that 154 (42%) were Luminal A low risk, 78 (21%) were Luminal A Ultralow risk and 132 (36%) were Luminal B High Risk. Analysis by race demonstrated a significantly higher percentage of high risk tumors in African-American women including a higher percentage of basal cancers (26%) as compared to Caucasian women (10%). Of note, 51 patients in the pilot study had additional OncotypeDX (ODX) testing on subsequent surgical resection. There was fair correlation between the assays with the majority of the low risk MPT having low risk ODX scores (<=25) and the high risk MPT having high risk ODX scores (>25), though MPT identified more patients as being high risk. The COVID-19 pandemic altered plans to assess time to treat and treatment interventions as initially intended. However, the knowledge of genomic result enhanced the ability to triage patients, allowing those patients with low risk tumors to begin endocrine therapy and delay surgery. Use of preoperative hormone therapy was considered more often in place of neoadjuvant chemotherapy in patients with low genomic risk ER+/HER2- patients. Because of the continued feedback indicating positive impact, the pilot ultimately was extended to 11 months to allow time for formal implementation. Conclusions: Genomic testing using the MPT/BPT assay on core biopsy samples with at least 3 mm yields results 97% of the time with an average TAT of 11 days from biopsy date to result. The genomic information at the time of initial diagnosis impacted patient care most notably in the ER+ setting. The results led to the immediate implementation of direct reflex testing of all newly diagnosed ER+ and HER2- or IHC 2+ cancers by pathology after the initial pilot phase. Citation Format: Hannah Gilmore, Philip Bomeisl, Alberto Montero. Genomic testing on breast cancer core biopsy material is feasible and provides useful treatment information [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-12.

Impact of oncotype Dx score on treatment and long-term outcomes.

e12518 Background: Oncotype dx is a 21 gene breast cancer assay that helps predict benefit of chemotherapy in early-stage hormone receptor positive (HR+), HER2 negative, 0 to 3 node positive breast cancer as reported by TAILORx and RxPonder trials. Both trials found no benefit of adjuvant therapy in mid-range scores of 11-25 with the exception of some benefit in age under 50 or premenopausal status, no benefit if score was 0-10, and benefit of chemotherapy if >25. Methods: All breast cancer patients between 2019-2020 were chart checked to evaluate oncotype dx scores. Patient characteristics were analyzed between oncotype dx scores of 0-10, 11-25, and >25 using X square tests. 2000-2020 institutional cancer registry data was analyzed to understand recurrence and mortality in patients with oncotype dx testing. Results: 173 patients had oncotype dx testing between 2019-2020, and most were HR+, HER2-, and had 0-3 lymph nodes. There was no difference in race or ethnicity between the groups of oncotype dx scores (Table), and average age at diagnosis for all three groups was 58 years. More patients with lower oncotype dx score had hormone therapy, but this was not significant (0-10 at 93.6%, 11-25 at 90.8%, and >25 at 82.1%, p=0.26). Patients with a higher oncotype score were significantly more likely to have chemotherapy (0-10 at 0%, 11-25 at 17.3%, and >25 at 82.1%, p<0.01). When looking at long term outcomes, the mortality rate was highest in the 11-25 score group at 9.5%, but was not significantly higher than 0-10 at 4.7% and >25 at 2.1% (p=0.15). The recurrence was highest in the 0-10 group at 5.4%, but not significant compared to the 11-25 group at 4.1% and >25 group at 4.2% (p=0.09). Conclusions: Race, ethnicity, and age does not impact predisposition to high oncotype dx score, which is interesting since literature shows minority women have higher mortality rates. This could be because oncotype dx looks at early-stage breast cancers and many minority women have later stages at diagnosis. There was no difference in which group received hormone therapy and there was significantly higher rate of chemotherapy administration in patients with scores >25, which is consistent with prospective trial recommendations. When evaluating long term outcomes between oncotype dx groups over 20 years, there was no significant difference in recurrence of disease or mortality indicating that oncotype dx scoring accurately predicted overall benefit of chemotherapy.[Table: see text]

Disparities in breast cancer by race and ethnicity.

e18526 Background: Breast cancer is the most common female malignancy. While there have been significant advances in diagnosis and treatment of breast cancer, there are gaps in care leading to high mortality rates in low socio-economic populations and ethnic minorities. This inequality is attributed to poor access to care and later stages at diagnosis. Methods: All female breast cancer patients between 2000-2020 (N=8,444) were included. Statistical analysis was done with X2 testing for categorical variables and T-tests for continuous variables. A univariate logistic regression was used to understand impact of each characteristic. Results: Black women were more likely to have poor prognostic factors for breast cancer compared to white women: distant metastatic disease at diagnosis (4.6% vs 3.2%, p=0.02), triple negative disease (25% vs 13.6%, p<0.01), high oncotype dx score >25 (37.2% vs 26.1%, p=0.04), recurrence (14.9% vs 12.1%, p=0.04), and mortality rate (24.2% vs 15.6%, p<0.01). Despite these high-risk factors, white women were more likely to have a mastectomy than black women (43.8% vs 35.4%, p<0.01), and the average age at diagnosis was higher in black women at 59.2±13.5 years compared to white women at 57.5±12.8 years (p<0.01). The most prominent poor prognostic factor in black women was having triple negative breast cancer with OR 2.13 (95% CI 1.7- 2.6) compared to others in Table. Hispanic women were more likely to have higher stage at diagnosis (OR 1.21), lymph node involvement (OR 1.03), metastatic disease (OR 1.43), and tumor size >1cm (OR 1.06) than nonHispanic women, but only lymph node involvement at diagnosis was statistically significant (29.1% vs 24.5%, p=0.02). Conclusions: There is a high prevalence of racial and ethnic disparities in women with breast cancer. Black women are more likely to have poor prognostic factors including metastatic disease at diagnosis and triple negative breast cancer, leading to higher recurrence and mortality rates. Hispanic women are also more likely to have poor prognostic factors, but this data was not statistically significant due to small sample size. Efforts to improve access to health care leading to earlier diagnosis may decrease the gap in mortality rate for minority women with predisposition to high-risk malignancies.[Table: see text]

Exploring the effects of genomic testing on fear of cancer recurrence among breast cancer survivors.

Fear of cancer recurrence (FCR) is the greatest unmet psychosocial need among breast cancer survivors (BCS). The Oncotype Dx® test predicts the 10-year risk of distant recurrence and benefit of adjuvant chemotherapy among women with early stage hormone receptor-positive breast cancer. Despite the test's clinical utility, psychosocial responses are poorly understood. A descriptive cross-sectional study was conducted to explore associations between Oncotype Dx® test results (Recurrence Score [RS]) and FCR, health-related quality of life (HRQOL), distress, anxiety, depression, illness representation and perceived risk. Bivariate analyses were used to examine the associations between variables followed by multiple linear regression to examine predictors of FCR. Greater FCR was associated with higher distress, anxiety, depression, illness representation and poorer HRQOL. BCS's with a high Oncotype Dx® RS reported higher overall fear (p=0.013) and greater perceived consequences of their cancer (p=0.034) compared to BCS's with a low RS. Using multiple linear regression, anxiety ( =0.21, p=0.016), greater emotional response =0.45, p<0.001) and perceived consequences ( =0.18, p=0.039) of illness explained 58% of the variance (p<0.001) in FCR. BCS's with higher risk of recurrence may experience higher FCR. However, for FCR, modifiable factors such as anxiety and illness representation (greater emotional response and perceived consequences of illness) may be more important than non-modifiable factors such as Oncotype Dx® test results and age. Further research is needed to develop personalized interventions to improve BCS's outcomes.

Can Oncotype DX testing be omitted in invasive breast cancer patients with clinicopathologic factors predicting very high pretest probability of a concordant result?

To determine if clinicopathologic (CP) factors could identify patients at "very low" and/or "very high" pretest probability of a high Oncotype DX (ODX) score. A retrospective analysis of all patients that had ODX testing 2008-2018 at a single institution. Of 215 patients, all 16 (7.4%) with "all high" risk CP factors had high ODX scores, and all 45 (20.9%) over age 50 with "all low" risk CP factors had ODX recommendations for no chemotherapy. Oncotype DX results did not change chemotherapy recommendations in those with "very low" or "very high" pretest probability of high ODX scores.

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 3298: Oncotype DX recurrence score: Implications for disparities in receipt of chemotherapy and breast cancer-specific mortality in Georgia

Abstract Background: Among women diagnosed with stage I-IIIa, node negative or positive (1-3), hormone receptor positive (HR+) and HER2 negative breast cancer (BC), the Oncotype DX recurrence score is used to guide chemotherapy treatment decisions. There is limited evidence on differences in the distribution of recurrence scores among non-Hispanic Black women (NHB), and whether this could contribute to the well-documented racial disparities in BC-specific mortality. The objective of this study was to evaluate the role of Oncotype DX recurrence score on racial disparities in BC-specific mortality between black and white women in Georgia. Methods: In this study, patients were identified from the Georgia Cancer Registry. We included 4562 non-Hispanic White (NHW) and 1353 NHB women with an initial diagnosis of stage I-III HR+ breast cancer in Georgia (2010-2014), with a corresponding Oncotype DX recurrence score from Genomic Health, Inc. Logistic regression was used to estimate the odds of chemotherapy receipt between NHB and NHW women by Oncotype DX recurrence score (low [&amp;lt;18], medium [18-30], and high [≥31]). Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing BC-specific mortality rates by both race and recurrence score. Results: Compared with NHW breast cancer patients, NHB women were more likely to be classified with a high recurrence score (11% vs. 7%), and less likely to be classified with a low risk of recurrence (53% vs. 59%). In the age-adjusted models, NHB women with a high recurrence score were less likely to receive chemotherapy (OR=0.60, 95%CI 0.35, 1.04), however there was no difference in receipt of chemotherapy between NHB and NHW women with low or medium recurrence risk scores. After adjusting for age, we observed that NHB women with a low recurrence score had 3.05 times the hazard of BC-specifc mortality (95%CI 1.29, 7.04) compared to NHW women. Among women with a medium or high recurrence score we did not observe a racial disparity in BC mortality (HRhigh vs. low=1.49, 95%CI 0.51, 4.37). Conclusion: Our results indicate variation in receipt of chemotherapy by race, particularly among NHB women with a high Oncotype DX score. However, we observed the most pronounced racial disparity in BC-specific mortality among women with low Oncotype Dx recurrence scores. These findings should be replicated in larger studies with robust numbers of NHB women. Additional research is needed to understand differences in chemotherapy treatment decisions and validation of the Oncotype DX recurrence score cut points in diverse populations. Citation Format: Lindsay J. Collin, Brittany Crawford, Ming Yan, Renjian Jiang, Kevin Ward, Mylin Torres, Keerthi Gogineni, Preeti Subhedar, Lauren E. McCullough. Oncotype DX recurrence score: Implications for disparities in receipt of chemotherapy and breast cancer-specific mortality in Georgia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3298.

Clinical value of Ki67 in risk-stratifying HR-positive breast cancer.

e12540 Background: Oncotype DX (ODX) is a validated clinical tool requiring efficient utilization. Ki67 protein immunohistochemistry (IHC) may represent a screening approach correlating with the Recurrence score (RS) in resource limited setting. Methods: We retrospectively studied 242 patients (Jan. 1989 – Oct. 2017) across rural practices in NM. Median time to follow-up was 8.9 (0.03, 26.8) yrs. ODX candidates evaluated included node positive (NP), negative (NN), hormone receptor (HR) positive and HER2 negative cohort. Ki67 &lt;20% (LKi-n=196) vs &gt;20% (HKi-n=46) was compared to Low/Intermediate (LODX-n=202) vs High risk ODX (HODX-n=40). Descriptive statistics, Chi-square, Kaplan Meier survival and Cox proportional hazard models were used. Results: Median age was 64 ± 13.2. Stage I (54.1%), II (42.6 %), and III (3.3%); Grade 1 (24.2%), 2 (46.7%), 3 (24.9%). LKi in (196/242) 81%, HKi in (46/242) 19%. LODX in (202/242) 83.4%, HODX in 40/242 (16.5%). LKi was associated with stage I (87%), II (78%) vs. Stage III (25%) (p=0.015). LKi was associated with lower grades 1 (100%), 2 (92%) vs grade 3 (40%) (p=&lt;0.001). LKi was associated with LODX (190/242) 94% and HKi with HODX (34/40) 85% (p &lt;0.001). ODX recategorized 3% (6/196) LKi into HODX and 26% (12/46) HKi to LODX. LKi vs HKi 10-year FFP was 0.97 + 0.01 vs 0.73 + 0.08 HR 8.31 (3.12, 22.14)(p=&lt;0.01) and 10-year OS was 0.87 + 0.03 vs 0.78 + 0.08 HR 1.77 (0.84, 3.78) (p=0.13), respectively. Ten-year OS in LKi was 0.98 + 0.02 vs 0.97 + 0.02 HR 0.42 (0.04, 3.62) (p= 0.43) with (n=46) or without (n=121) adjuvant chemotherapy respectively. Conclusions: LKi is predictive of excellent outcomes. It may have a role in risk stratification when access to ODX is limited. Lack of standardization of Ki67 reiterates the value of ODX. Prospective data are needed to confirm these findings.

Clinical practice patterns on the use of adjuvant bisphosphonate for early breast cancer: A Canadian perspective.

e12002 Background: Adjuvant bisphosphonates (ABPs) in menopausal women with early breast cancer (EBC) decrease the risk of BC relapse and modestly improve overall survival (OS). In the era of personalized medicine, a one size fits all approach is not ideal–it is important to identify the subgroup of patients who may not derive a clinically meaningful benefit to avoid over treatment, unnecessary toxicity, and optimize resource utilization. Objectives: To better characterize how Canadian medical oncologists (MOs) use ABPs and whether practice patterns are concordant with the CCO/ASCO guideline. Methods: A brief survey was circulated by e-mail to 618 Canadian MOs between Nov 2017 - May 2018. Questions were designed to gather data on demographics, patient selection, choice of bisphosphonate, schedule/duration of treatment and barriers to use. No incentive was provided. Results: Sixty-eight MOs from 8 Canadian provinces completed the survey (response rate 11.0%). Most practiced in Ontario (65.7%) and just over half (51.5%) were community oncologists. MOs offered ABPs to 52.2% of menopausal women with EBC. Use was higher in the community compared to the academic setting (p=0.049). Most used zoledronic acid (85.3%) every 6 months (95.6%) for 3 years (69.1%) and started treatment within 3 months of completing adjuvant chemotherapy/radiation (67.7%). Factors associated with use of ABPs were: high Oncotype Dx score (89.1%), high tumor grade (72.1%), triple negative disease (63.6%), osteoporosis (87.7%)/osteopenia (83.9%) and use of aromatase Inhibitor (75.0%). The most common factor precluding use of ABPs was presence of comorbidities (89.7%). About 1/3rd indicated they would offer ABPs to women with stage I HR positive/Her2 negative EBC. Conclusions: Canadian MOs have added intravenous ABPs to their armamentarium of therapies in keeping with the spirit of the recent guideline. High-risk disease features and low bone density appear to be influencing the decision-making process. Further work aimed at identifying those patients who are unlikely to benefit from treatment is needed.

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.

Abstract P3-11-04: A model to predict high-risk Oncotype DX scores as defined by the TailorX trial: A report from the National Cancer Data Base

Abstract Background: Results from the TailorX clinical trial demonstrated a survival benefit of chemotherapy in those with high-risk (&amp;gt;25) Oncotype DX scores as well as in some patients ≤50yo with intermediate (16-25) scores. The objective of this study was to develop a model that could predict a high-risk Oncotype DX score based on tumor features alone. Methods: From 2010-2015, 84,549 breast cancer patients with Oncotype DX scores were selected from the National Cancer Data Base. Seven pathologic variables including age, estrogen and progesterone receptor status, histologic subtype, lymphovascular invasion (LVI), grade, and tumor size were used to predict high-risk (&amp;gt;25) Oncotype DX scores using logistic regression. A similar analysis was performed on women ≤50yo to predict low (&amp;lt;15) and intermediate (16-25) scores. Nomograms were created for models using bootstrap estimation method of the model coefficients. Cutoffs with at least 80% positive predictive value (PPV) were chosen to classify patients into high or low-risk Oncotype DX score groups. Accuracy of these predictions were developed in a training set and validated in a testing set. Results: For patients &amp;gt;50yo, 6,658 (15.1%) of patients had high-risk Oncotype DX scores. The model yielded a moderately strong C-index of 0.80 for Oncotype DX score of &amp;gt;25. For women ≤50yo, 2,044 (13.5%) were high-risk, 5,760 (38.1%) were intermediate-risk and 7,316 (48.4%) were low-risk. The C-index for women ≤50yo was 0.81 for prediction of Oncotype DX score of &amp;gt;25. C-indexes for intermediate and low risk scores were not strong enough to use for prediction (0.54 and 0.67). Estrogen receptor status, progesterone receptor status and grade were the strongest independent predictors of high-risk Oncotype DX scores in women &amp;gt;50yo and ≤50yo. Age was not a good predictor of high-risk scores in women &amp;gt;50yo. When our nomogram was used in the training set, the PPV of a high-risk Oncotype score was 80% with a negative predictive value (NPV) of 87%, sensitivity of 19% and specificity of 99%. In the testing set, PPV was 81%, with a NPV of 87%, sensitivity of 19% and specificity of 99%. Conclusion: A model incorporating tumor factors can predict a high-risk Oncotype DX score as defined by the recent TailorX trial in all age groups. The model is of limited value in predicting intermediate-risk Oncotype DX scores in women of age ≤50. In resource-constrained healthcare systems, such a model can help identify high risk patients who would benefit from adjuvant chemotherapy without incurring the cost of an Oncotype DX test. Citation Format: Pesce C, Kuchta K, Wang E, Yao K, El-Tamer M. A model to predict high-risk Oncotype DX scores as defined by the TailorX trial: A report from the National Cancer Data Base [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 P3-11-04.

Abstract P4-08-12: Comparative analyses of the prognostic value of oncotype and mammaprint using the National Cancer Database

Abstract INTRODUCTION: Majority of the approximately 40,610 deaths from metastatic breast cancer in the US each year occur in women with hormone receptor positive breast cancer who recur after treatment for early stage disease. Genomic analysis is increasingly used to personalize breast cancer treatment for women with early breast cancer resulting in AJCC 8 modification of TNM staging. The 70-gene Mammaprint was developed using both ER- and ER+ breast tissue samples, while the 21-gene Oncotype DX (ODX) assay was developed using only ER+ breast tissue. Previous studies found that the two genomic assays gave discordant testing results. OBJECTIVE: To compare the performance of Mammaprint and Oncotype DX in assigning prognosis in early stage hormone receptor positive breast cancer. METHOD: A retrospective 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), 2010-2014. Using the propensity score matching method, we defined two groups of patients with similar clinical and demographic characteristics; one group received ODX and another received Mammaprint. The groups were matched by clinicopathologic and demographic factors. We examined the association between ODX or Mammaprint and overall survival using Log-rank test and Cox models in the two groups separately. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated as strength of association. The prognostic values were evaluated using c-index (i.e. area under ROC curve). RESULTS: Of 320,276 eligible patients with breast cancer, 41.5% received ODX and 1.3% received Mammaprint testing. The use of ODX increased from 34.3% in 2010 to 45.2% in 2014, while the use of Mammaprint increased from 0.5% in 2010 to 2.0% in 2014. After propensity score matching, we identified 3319 patients who received ODX and matched to 3319 patients who received Mammaprint. Compared to patients with a low risk Mammaprint score (n=1915), patients with a high risk Mammaprint score (n=1404) had 4.53-fold increased risk of dying (95% CI 2.79-7.36). The c-index for Mammaprint was 0.683. Relative to patients with a low ODX recurrence score (n=1927), the HR for intermediate ODX score was 1.23 (95% CI 0.76-1.98) and the HR for high ODX score was 3.62 (95% CI 2.21-5.94). The c-index for ODX was 0.601. In patients with ODX testing, 28.2% received chemotherapy. In patients with Mammaprint testing, 42.4% received chemotherapy. Based on MINDACT's modification of Adjuvant!Online, 49.2% patients were assigned to the clinical high risk group, including 22.3% to the clinical high risk/genomic low risk (C-high/G-low) subgroup and 26.9% to the C-high/G-high subgroup. The percentage of patients receiving chemotherapy with C-low/G-low, C-low/G-high, C-high/G-low, and C-high/G-high were 4.3%, 70.4%, 32.2%, and 84.9%, respectively. CONCLUSION: The findings from our preliminary study suggest that Mammaprint may achieve better separation of high risk from low risk patients. However, it is possible that having more genes in multigene assays would better capture the heterogeneity of hormone receptor positive breast cancer and guide choice of optimal systemic therapy to reduce risk of metastases. Citation Format: Ibraheem AF, Olopade O, Huo D. Comparative analyses of the prognostic value of oncotype and mammaprint using the National Cancer Database [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 P4-08-12.

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.

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.

Abstract P4-09-12: Quantitative image features of nuclear and tubule architecture distinguish high and low oncotype DX risk categories of ductal carcinoma in situ from H&amp;E tissue images

Abstract Background: Ductal Carcinoma in Situ (DCIS) is a pre-invasive stage of breast cancer, where malignant cells line the duct but have not spread into other parts of the breast. Oncotype DX (ODX) is a genomic test, which divide patients into three risk of recurrence categories (Low, Intermediate, and High) to help physicians determine if patients require adjuvant therapy. However, ODX is expensive, tissue destructive, and has a turnaround time of 7-10 days. There has been an interest in the use of image analysis of routine H&amp;E histopathology slides to predict the course of the disease; the rationale being that the analytics are able to unearth subtle sub-visual cues regarding disease morphology that may escape visual examination. In this work, we evaluate the role of computer extracted features of nuclear morphology and the necrotic regions from surgically resected specimens to predict ODX categories in patients with DCIS. Methods: H&amp;E slides from breast tissue of 37 patients who were diagnosed with DCIS and underwent a lumpectomy were acquired. Nine of the 37 had high ODX score (higher than 54), while the rest had a low score (lower than 39). All the slides were digitized on a Philips slide scanner. For each image, a watershed algorithm segmented the individual nuclei, which were used to generate 230 nuclei features including nuclear architecture, nuclear shape and nuclear texture features within each candidate breast duct. In addition, we captured the area of necrosis and empty lumen region inside breast ducts to generate features pertaining to tubule packing. The average feature values for each patient were calculated across all the breast ducts in each slide. A 3-fold cross validation scheme with 50 repetitions was used with the Support Vector Machine (SVM) classifier to predict the ODX risk category for each patient. We used a covariance algorithm to select the top 4 features that were independent of each other but relevant to the ODX class label. Results: The top ranked features included features from three categories: nuclei architectural features (standard deviation of triangle area in Delaunay graph, skewness of edge length in Cell Cluster Graph), nuclear texture (standard deviation of Haralick matrix intensity) possibly reflecting chromatin patterns in the cell, and the Tubule Packing Ratio, a measure of the ratio of necrosis area and empty lumen area inside the breast ducts compared to the whole breast duct area. The SVM in conjunction with these 4 features yielded a mean area under receive operator characteristic curve (AUC) of 0.95 in correctly predicting high and low ODX risk categories. Conclusion: We found that our histomorphometry features pertaining to nuclear arrangement, nuclear texture and necrosis could differentiate between DCIS patients with high and low ODX risk categories. Additional independent validation of the approach is needed to confirm the preliminary findings presented here. Citation Format: Li H, Whitney J, Thawani R, Gilmore H, Badve S, Madabhushi A. Quantitative image features of nuclear and tubule architecture distinguish high and low oncotype DX risk categories of ductal carcinoma in situ from H&amp;E tissue images [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 P4-09-12.

Abstract P1-07-28: Retrospective analysis of clinicopathologic features predictive of oncotype DX discordance in estrogen receptor positive, node negative breast cancer patients

Abstract BACKGROUND: Oncotype DX (ODX) is a validated recurrence score (RS) used to predict the risk of recurrence and benefit of chemotherapy in ER positive, node negative breast cancer patients. Prior to ODX, treatment recommendations regarding adjuvant chemotherapy and mortality approximation have taken into account clinical and pathologic risk factors. A discordance rate of 7-19% between risk allocating pathologic factors and ODX RS has been previously reported with progesterone receptor (PR) negativity noted as a defining clinical feature in numerous cases. The association between other clinicopathologic features and discordance is less certain. METHODS: ODX data and clinicopathologic features were retrospectively reviewed for 724 breast cancer tumors belonging to 704 patients between 2006 and 2016. ODX discordance was defined as either 1-step discordance or 2-step discordance between ODX risk group (low, intermediate, high) and tumor grade (TG) (well differentiated, moderately differentiated, poorly differentiated). Tumors with 1-step discordance received a discordance score (DS) of 1 while those with 2-step discordance received a DS of 2. The database was subsequently analyzed using Paik's RS cutoffs as well as those outlined in the TAILORx trial. An odds ratio (OR) of &amp;gt;1 was consistent with discordance. RESULTS: Among 724 tumor samples, ODX ER score (p=0.000), ODX PR score (p=0.000), ODX HER2 score (p=0.000), TG (p=0.000), mitotic count (MC) (p=0.0012), DCIS grade (p=0.0046), DCIS type (comedo necrosis vs. non-comedo necrosis) (p=0.0335) and micropapillary features (p=0.0044) were significantly associated with RS. Median age of cohort was 59 years and median tumor size was 1.2 cm. Of 724 tumors, 619 from 604 subjects were eligible for assessment of discordance. Median RS was 16. Using Paik's RS cutoffs, 64.3% discordance was observed: 52.5% 1-step discordance (DS 1) and 11.8% 2-step discordance (DS 2). The TAILORx categorization yielded a discordance rate of 44.3%: 40.1% 1-step discordance and 4.2% 2-step discordance. On univariate analysis and using Paik's RS cutoffs, young age (p= 0.0240), high MC (p=0.0006), large tumor size (&amp;gt;20 mm) (p=0.0209), the presence of DCIS (p=0.0480), high DCIS grade (p= 0.0033), and high ODX PR and ER scores (p= 0.0000) were significant clinicopathologic features predictive of discordance. On multivariate analysis, high MC (p= 0.0000), high ODX PR and ER scores (p=0.0000) remained significant as well as premenopausal status (p=0.026). Per TAILORx cutoffs, univariate analysis revealed younger age (p= 0.0060), high MC (p= 0.0270), premenopausal status (p= 0.0124), and high ODX PR and ER scores (p= 0.0000) as significant for discordance. On multivariate analysis, high ODX PR and ER scores (p= 0.0000) remained significant. CONCLUSION: In this retrospective ODX database, premenopausal status, high MC, high ODX PR and ER scores as per Paik's RS cutoffs were significant predictors for ODX discordance while high ODX PR and ER scores were significant predictors per the RS's outlined in the TAILORx trial. RS cutoffs per the TAILORX trial appear to create less discordance between RS and TG than the original cutoffs outlined by Paik and colleagues. Citation Format: Cascetta KP, Zimmerman BS, Eggert L, Molot MC, Ru M, Nayak A, Bleiweiss I, Tiersten A. Retrospective analysis of clinicopathologic features predictive of oncotype DX discordance in estrogen receptor positive, node negative breast cancer patients [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 P1-07-28.