Intermediate Risk Recurrence Score Research Articles

The Added Prognostic Value of Oncotype Recurrence Score to AJCC Prognostic Staging System in Stage III ER+/HER2- Breast Cancer.

Prognostic prediction based on prognostic stage (PS) with the Oncotype DX recurrence score (RS) has not been validated in stage III ER+/HER2- breast cancer. This study aimed to evaluate the added prognostic significance of RS incorporated with the PS system and to compare the prognostic prediction improvement with anatomic TNM stage (AS) using nomogram construction. The SEER database was indexed to identify ER+/HER2- invasive ductal or lobular breast cancer in AS IIIA-IIIC with RS results diagnosed from 2004 to 2013. Patients with RS < 18, 18-30 and > 30 were categorized into low-, intermediate- and high-risk RS groups. Comparisons of the distribution of clinical-pathologic characteristics among RS risk groups were performed using Pearson's chi-square test. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier method and compared across RS or PS by log-rank test. Cox regression was used to evaluate the factors independently related to BCSS. A nomogram comprised of PS and RS was constructed with discrimination, calibration and clinical benefit evaluated. Altogether 629 patients who received RS were enrolled. There were 326 cases (51.8%) with low-risk RS, 237 (37.7%) with intermediate-risk RS and 66 (10.5%) with high-risk RS; 344 patients (54.7%) had PS IB, 84 (13.4%) had IIB, 150 (23.8%) had IIIA, 46 (7.3%) had IIIB, and only 5 had (0.8%) IIIC. Both PS and RS were independent prognostic factors for BCSS. There were significant or trends of differences in survival among RS within subtypes stratified by PS. There were significant differences in survival among PS only within intermediate-risk RS. A nomogram prediction 5-year BCSS was constructed with a c-index of 0.811. Lower histologic grade, positive PR and fewer positive lymph nodes were independently correlated with low-risk RS. PS incorporated with RS had improved prognostic significance for stage III ER+/HER 2- breast cancer.

Application of RSClin to guide treatment recommendations for premenopausal patients with early-stage hormone-positive breast cancer and intermediate risk oncotype recurrence scores.

e12511 Background: The RSClin model, which incorporates the Oncotype Recurrence Score (RS) and clinicopathologic features, was recently developed to further tailor prognosis and prediction of chemotherapy benefit for patients with early-stage hormone positive (HR+) breast cancer (BC) (Sparano et al, 2020). The RSClin calculator is available online to assist treatment planning for situations where chemotherapy benefit is uncertain. Covariates include Oncotype RS, tumor grade, tumor size and patient age. The risk calculator generates a 10-year distant recurrence risk and absolute chemotherapy benefit. This tool may be especially helpful to determine treatment management for premenopausal patients with early-stage HR+ BC with intermediate risk (IR) Oncotype RS (16-25). We retrospectively applied RSClin to this patient population to determine if it would have changed treatment recommendations. Methods: We identified premenopausal women with node-negative early-stage BC with IR RS (16-25) within our large Oncotype database. Using the RSClin model, we selected &gt;5% absolute chemotherapy benefit as a reasonable cutoff to recommend chemotherapy. We compared the treatment recommendation based on RSClin with the treatment previously recommended by breast oncologists at our large academic medical center in New York City. Results: There were 86 patients who met criteria with a median age of 46 years. Of these, 26 patients (30%) were recommended chemotherapy plus endocrine therapy (ET) and 60 (70%) were recommended ET alone. After applying the RSClin model (data available for 83/86 patients), 19 (23%) would have resulted in a change in treatment recommendation and 64 (77%) would have remained unchanged. Overall, 8 (10%) would have withheld chemotherapy when it was previously offered and 11 (13%) would have recommended chemotherapy when it was previously excluded. There were 8 (9%) secondary invasive breast events in this population, with 2 (2%) being ipsilateral, 3 (3%) being contralateral and 3 (3%) metastatic at a median follow up of 46.9 months. Conclusions: The RSClin model would have changed management of premenopausal patients with IR RS in 23% of patients. This model, although not yet prospectively validated, may help individualize therapy for patients with less definitive treatment plans. Using RSClin, we can aim to minimize recurrence rates and avoid unnecessary chemotherapy in selected patients. This model is easy to apply and will have important clinical utility moving forward.

Comprehensive analysis of the 21-gene recurrence score in invasive ductal breast carcinoma with or without ductal carcinoma in situ component

BackgroundInvasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear.MethodsConsecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients.ResultsA total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis.ConclusionsIDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.

Oncotype DX Breast Recurrence Score Distribution and Chemotherapy Benefit Among Women of Different Age Groups With HR-Positive, HER2-Negative, Node-Negative Breast Cancer in the SEER Database.

Objective: To explore the distribution of Oncotype DX Breast Recurrence Score (RS), the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to detailed age groups in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-negative (HR+/HER2−/N0) breast cancer.Methods: This was an extensive, comprehensive, population-based retrospective study. Data on individuals with breast cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program. The cohort was divided into five groups by age (≤ 35, 36–50, 51–65, 66–80, >80 years). RS distribution and chemotherapy proportion among different age groups were analyzed, and the overall survivals between patients receiving chemotherapy and those not/unknown were compared in each age group.Results: The study cohort comprised 49,539 patients and the largest age group was 51–65 years. The percentage of patients with low-risk RS (0–10) increased with age, whereas those with intermediate-risk RS (11–25) decreased with age (except for the group of 36–50 years, which had the highest rate of intermediate-risk RS). The age group ≤35 years has the greatest rate of high-risk RS (26–100). The proportion of receiving chemotherapy decreased with age in all RS risk categories. Overall survival was benefited by chemotherapy only in the age group of 66–80 years with intermediate- and high-risk RS, and chemotherapy seemed to do more harm than good for patients older than 80 years.Conclusions: In the present study, we identified the distribution of RS, the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to a detailed age grouping for women with HR+/HER2−/N0 breast cancer, which may help in making individualized clinical decisions.

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

Abstract Introduction: Oncotype DX (ODX) Recurrence Score (RS) is a gene-expression assay that provides prognostic and predictive information in hormonal-receptor positive (HR +), human epidermal growth factor receptor 2 negative (HER2-), axilary lymph node negative (LN-) disease. It estimates the 10 year-risk of distant recurrence and it is recommended to asses this issue and the potential benefit of adjuvant systemic therapy in early stage breast cancer (ESBC). (JCO 2016, NCCN 2019). Objective: To evaluate the impact of RS on our adjuvant treatment decision making and follow-up (FU). Materials and methods: Observational, prospective single institution study. Eligible patients (pts) were diagnosed between September 2012 and December 2018 with HR+, HER2 -, N0 and N+ (N1mic) ESBC for who underwent ODX assay. Criteria for ordered ODX assay were established by the group of experts from the Basque Country Health System. Treatment recommendations were documented before and after the conventional RS results. We reviewed clinical and pathology reports for FU and events. Descriptive statistics were used to summarize patient and tumor characteristics and changes in oncologists’ treatment recommendations. Mc Nemar’s test was used to identify how these tests impact in decisión. Results: N=337 pts. Median age was 57 years (SD 9,11); women 328 pts (97%); premenopausical 114 (34%); conservative surgery 271 pts (80%); sentinel node 318 pts (94 %); pN0: 248 pts (74%), pN1mic: 89 (26%); tumor size: pT1a-b: 41 pts (12 %), pT1c: 234 pts (69%) and pT2: 62 pts (18%); histologic type: ductal 280 pts (83%); histological grade: G1 49 pts (16%), G2 250 pts (74 %), G3 34 pts (10%); Ki 67 index &amp;gt;=13: 221 pts (66 %); progesterone receptors: positives: 304 pts (90%); presence of lymphovascular invasión:36 pts (11%). Treatment decision before assay was hormonal therapy (HT) in 242 pts (72 %) and chemotherapy (CT) in 95 pts (28 %). Conventional RS were: low risk RS&amp;lt;18 (LR): 180 pts (53%), intermediate risk RS 18-30 (IR): 135 pts (40%) and high risk RS &amp;gt;30 (HR): 22 pts (7%). TAILORx RS cutpoints were: LR RS &amp;lt;11: 78 pts (23%), IR RS 11-25: 207 pts (61%), HR RS &amp;gt;25: 52 pts (15%). Post-assay treatment: 278 pts (82.5%) received HT and 59 pts (17.5 %) CT. Treatment recomendation pre and post ODX assay changed in 17,5% of pts: in 10,5% from CT to HT and 7% from HT to CT. The McNemar's test was significant value (0.000). With a median FU of 35 months (range 1-77) there were 5 events: (1.5%): 1 local (0.3%) and 4 distant (1.2%). Conclusions: In our cohort, the 82.5% of pts received HT. The treatment decisión changed 17.5% of pts. The ODX avoided CT in 10.5% of 38 pts (28% pre and 17.5% post). At this time, insufficient median FU and number of events are available to examine long-term prognosis and CT benefit. Citation Format: Maria Purificacion Martínez del Prado, Borja López de San Vicente, Juan Fernando Arango Arteaga, Jairo Legaspi Folgueira, Ane Zumárraga Cuesta, Fernando Pikabea Diaz, Patricia Novas Vidal, María López Santillán, Laura Sande Sardina, Maitane Nuño Escolástico, María Teresa Abad Villar, Maria Ángeles Sala Gonzalez, Covadonga Figaredo Berjano, María Teresa Pérez Hoyos, Elena Galve Calvo. Oncotype DX assay’s real world data in early stage breast cancer patients. Outcomes of a cohort treated in the Basurto University Hospital, Spain [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-05.

Impact of 21-gene recurrence score testing on adjuvant chemotherapy decision making in older patients with breast cancer

PurposeTo evaluate the role of 21-gene recurrence score (RS) assay in adjuvant chemotherapy decision-making among older patients with early breast cancer. MethodsConsecutive hormonal receptor-positive, aged ≥60 patients with breast cancer were enrolled from Shanghai Ruijin Hospital between January 2014 and December 2017. Treatment decisions were made by multi-disciplinary team (MDT) before and after 21-gene RS testing, and the actual treatment for each patient was also analyzed. ResultsA total of 511 patients were enrolled, with 331 (64.8%) aged between 60 and 69, 140 (27.4%) between 70 and 79, and 40 (7.8%) over 80 years. There were 138 (27.0%), 287 (56.2%), and 86 (16.8%) patients classified as low, intermediate, and high risk RS, respectively. Multivariable analysis demonstrated that age, tumor stage, nodal status, PR expression, Ki-67, and 21-gene RS were independent impact factors for chemotherapy recommendations (P < .05). Patients with high risk RS and intermediate risk RS (both P < .001) were more often recommended to receive chemotherapy than patients with low risk RS. Treatment recommendations changed in 74 (14.5%) patients after 21-gene RS testing: 17 (3.3%) from chemotherapy to no chemotherapy and 57 (11.2%) from no chemotherapy to chemotherapy. Overall compliance rate to MDT recommendation after 21-gene RS testing was 95.7%. ConclusionAn intermediate and/or high risk 21-gene RS assay was independently associated with receiving adjuvant chemotherapy among older patients with breast cancer. However, it showed a limited impact on adjuvant chemotherapy decision-making. After 21-gene RS testing, compliance with MDT recommendation was relatively high in older patients with breast cancer.

Breast cancer-specific survival outcomes among patients based on 21-gene recurrence score.

537 Background: The 21-gene recurrence assay predicts cancer recurrence rates and benefit from adjuvant chemotherapy among patients with hormone-receptor-positive breast cancer. The National Cancer Institute and Genomic Health collaborated to provide Recurrence Score (RS) results to complement data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: Using the SEER database with linked RS results, a cohort of female breast cancer patients, age greater than 20 years, was identified by RS (low: &lt; 18, intermediate: 18-30, high: &gt; 30) diagnosed between the years 2004 and 2007. A retrospective analysis was conducted to determine eight-year breast cancer-specific survival rates based on RS and other variables. Results: 10,318 patients were identified in the cohort. 5,194 had a low risk RS; 4,282 had an intermediate risk RS; 872 had a high risk RS. Histologic subtypes were: 7,459 infiltrating ductal carcinoma, 941 mixed infiltrating and lobular carcinoma, 933 lobular carcinoma, 327 mixed infiltrating ductal and other histology, 244 mucinous adenocarcinoma, 101 tubular adenocarcinoma, 45 mixed lobular and other histology, 268 other histologies. 644 low risk RS patients received chemotherapy (12.4%); 1,608 intermediate risk RS patients received chemotherapy (37.8%); 593 high risk patients received chemotherapy (68.0%). The eight-year breast cancer-specific survival rates (with 95% confidence intervals) among low risk RS patients without known chemotherapy administration was 98.9% (98.5, 99.2), and 98.4% (97.0, 99.1) with chemotherapy; intermediate risk RS patients without known chemotherapy was 97.0% (96.2, 97.6), and 96.9% (95.9, 97.7) with chemotherapy; high risk RS patients without known chemotherapy was 89.7% (85.4, 92.8), and 92.9% (90.4, 94.7) with chemotherapy. Conclusions: Among a large cohort of patients identified in a population-based cancer registry between 2004 and 2007, there was no statistically significant difference in eight-year breast cancer-specific survival rates among those who received chemotherapy and those who did not, regardless of RS risk group.

The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.

Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p =0.029) and after (p =0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.

Abstract P1-17-09: Use of Oncotype DX ® testing in nodal positive breast cancer patients: Real-life data from a single center in Munich, Germany

Abstract Introduction: Despite a large body of prospective studies showing good prognostic and predictive value of the Oncotype DX ® testing in ER+/HER2- early breast cancer patients after breast surgery, the test is currently not reimbursed in Germany by most national health insurance companies. Nevertheless, this multigene assay has been offered to node negative (N-) and increasingly to node positive (N1) patients with 1-3 positive lymph nodes by medical- and gyneco-oncologists for several years. The aim of the present study was to analyze real life data of the test in N1 patients from a German single center with special respect to the intermediate-risk recurrence score (RS) group and event-free survival (EFS). Patients and Methods: Patients with ER+/HER2- node positive breast cancer after breast surgery, to whom Oncotype DX ® testing was consecutively recommended by the interdisciplinary local tumor board from 1/2012 through 12/2016 at the Breast Center of the Red Cross Hospital Munich, Germany, were included in the study. Data was retrospectively retrieved from medical records (e.g. stage and histology), patient interviews as well as from the Munich Cancer Registry (outcome measurements). Patients were stratified according to Oncotype DX ® RS distribution (&amp;lt;11 low-risk, 11-25 intermediate risk and &amp;gt; 25 high-risk). Proportion of patients choosing adjuvant chemotherapy (CT) within the different RS groups and outcome were analyzed. Results: Oncotype DX ® testing was recommended and performed in 500 (17%) out of 2942 patients with ER+/HER2- tumors. Nodal status was positive in 159 (31.8%) of these patients. Patients with more than 3 positive lymph nodes and with missing data on follow-up were excluded, leaving 121 patients for the main analysis. According to RS distribution, n=19 (15.7%) were low-risk, n=83 (68.6%) intermediate-risk and n=19 (15.7%) high-risk, respectively. Although CT was generally discussed with all N1 patients with RS&amp;gt;10, only 39 patients (38.2%) of the intermediate and high-risk RS-group opted for systemic chemotherapy (24.1% of RS 11-25 and 100% of RS&amp;gt;25). In 13 of the patients (11%) within a median follow-up of 40 months an event occurred (4 loco-regional and 2 contralateral relapses, 5 distant metastases (3 bone, 2 visceral) and 2 deaths of other causes). Of those patients with events, three presented with RS &amp;lt;11, six with RS 11-25 and three with RS &amp;gt;25. In the intermediate group (n=83) EFS was 90% for patients receiving CT followed by endocrine therapy (ET) and 91.9% for patients with ET alone (p= 0,583). Conclusions: Using real life data from a large single breast center, only around 25% of patients with 1-3 positive lymph nodes from the intermediate RS group decided to undergo CT after Oncotype DX ® testing. The outcome of patients receiving ET only in this group was not inferior compared to CT followed by ET. Citation Format: Kriegmair A, Szeterlak N, Schrodi S, Stoetzer O, Pölcher M, Braun M. Use of Oncotype DX ® testing in nodal positive breast cancer patients: Real-life data from a single center in Munich, Germany [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 P1-17-09.

21-Gene Recurrence Score Assay and Outcomes of Adjuvant Radiotherapy in Elderly Women With Early-Stage Breast Cancer After Breast-Conserving Surgery.

Introduction: To assess the role of the 21-gene recurrence score (RS) assay on decision-making of postoperative radiotherapy (RT) following breast-conserving surgery (BCS) in elderly women with early-stage breast cancer.Methods: The 21-gene RS for elderly (≥65 years) women with stage T1–2N0M0 estrogen receptor-positive breast cancer who underwent BCS from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results program. We estimated the association of 21-gene RS and adjuvant RT related to breast cancer-specific survival (BCSS) using propensity score matching (PSM).Results: We identified 18,456 patients, of which 15,326 (83.0%) received postoperative RT. Of identified patients, 58.9, 34.0, and 7.1% of patients had a low-, intermediate-, and high-risk RS, respectively. Receipt of postoperative RT was not related to the year of diagnosis according to the 21-gene RS groups. Multivariate analysis suggested that receipt of postoperative RT was an independent predictor of better BCSS before (hazard ratio [HR] 0.587, 95% confidence interval [CI] 0.426–0.809, P = 0.001) and after (HR 0.613, 95%CI 0.390–0.963, P = 0.034) PSM. However, subgroups analyses indicated that receipt of postoperative RT was related to better BCSS in women with intermediate-risk RS before (HR 0.467, 95%CI 0.283–0.772, P = 0.003) and after (HR 0.389, 95%CI 0.179–0.846, P = 0.017) PSM, but not in women with low- and high-risk RS groups before and after PSM.Conclusions: Although causation cannot be implied, adjuvant RT in elderly women was associated with a greater effect size in patients with an intermediate-risk RS.

Abstract P5-08-06: Comparison of risk prediction with the 21-gene recurrence score (oncotype DX) and the 70-gene signature (MammaPrint) in patients with estrogen receptor-positive early stage breast cancer

Abstract Background: Gene expression profiling assays estimate prognosis &amp; predict benefit from adjuvant chemotherapy in patients (pts) with estrogen receptor positive (ER+) early stage breast cancer (ESBC). The 21-gene recurrence score (RS) and 70-gene signature (MP) are widely used assays. Pts may have both tests performed to adjudicate discordant results. We compared RS and MP in pts with both tests and evaluated their impact on adjuvant treatment decisions. Methods: This was a retrospective clinical cohort study from 5 centers from 2007-2014. Eligibility included ER+ ESBC with RS and MP results from the same tissue sample; exclusions included carcinoma in situ, primary metastatic disease, &amp; bilateral breast cancer. Two definitions of RS risk were evaluated (Genomic Health [GH] or TAILORx [TRx]): low risk (GH:0-17) or (TRx:0-10); intermediate risk (GH:18-30) or (TRx:11-25); and high risk (GH:&amp;gt;31) or (TRx:&amp;gt;26). Demographic, clinicopathologic (CP) data, and treatment decisions were extracted from medical records. Agreement was assessed between RS and MP using weighted kappa scores. CP factors were assessed with the t-test and chi-square test. Results: 123 pts were identified from UCSF or 4 US Oncology Network practices. 60 pts had low risk RS (GH); 27 were low risk by MP (45% agreement). 15 cases had a low risk RS (TRx); 9 were low risk by MP (60%). 10 pts had high risk RS (GH); 8 were high risk by MP (80.0%). Similarly, 18 cases had high risk (TRx) RS;16 were high risk by MP (88%). Using the RS GH risk definition, there was poor agreement for low risk RS/MP and high risk RS/MP (kappa=0.169). However, using the TRx RS risk definition, there was good agreement for low risk RS/ MP and high risk RS/MP (kappa=0.509). 53 pts had intermediate risk RS by (GH); by MP 16 were low risk (30%), and 37 were high risk (70%). 90 pts had an intermediate risk RS by TRx; by MP 34 were low risk (37.8%), and 56 were high risk by MP (62.2%). Using TRx RS increased the number of pts classified as intermediate risk compared to GH RS (73.2 vs 43.1%). Complete adjuvant treatment data were available for 90 patients. Of 40 pts with low risk RS (GH), 25% received chemotherapy associated with node status but not tumor size, grade, or MP. Of 10 pts with high risk RS (GH), 70% received chemotherapy without association with CP features or MP. For the 45 pts with intermediate risk RS (GH), 53% received chemotherapy, without correlation with CP features. Receipt of chemotherapy was positively associated with MP high risk, but this was not significant (odds ratio 2.08, 95% CI 0.54-8.01); p-0.29. Conclusion: Concordance in risk prediction between RS and MP was greater using RS defined by TRx compared to GH, and RS using TRx increases those categorized as intermediate risk. There appeared to be no correlation between CP features and decisions to use chemotherapy across risk groups. Interestingly, in those with intermediate risk RS (GH or TRx), there was a non-significant trend toward use of chemotherapy in those with high risk by MP. Although gene expression tests are used frequently to aid in treatment decisions in ESBC, considerable variation exists in their application in clinical practice. Citation Format: Jiang H, Denduluri N, Majure M, Favret A, Rugo HS. Comparison of risk prediction with the 21-gene recurrence score (oncotype DX) and the 70-gene signature (MammaPrint) in patients with estrogen receptor-positive early stage breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-06.

Abstract P5-15-01: Breast cancer specific survival in 38,568 patients with node negative hormone receptor positive invasive breast cancer and oncotype DX recurrence score results in the SEER database

Abstract Introduction: The SEER Program of the National Cancer Institute (NCI) is an authoritative source of cancer incidence and survival statistics, collecting population-based data for ∼28 percent of the US. As innovations in molecular testing are validated and recommended in guidelines, new genomic research models are needed to characterize their use and impact on patient outcomes in clinical practice. To that end, Genomic Health and SEER have collaborated to electronically supplement the SEER registries with Oncotype DX results. This first report characterizes breast cancer specific survival (BCSS) in node (N)- hormone receptor (HR)+ HER2- invasive breast cancer. Methods: The prospectively-defined population-biomarker-outcomes linkage had objectives, analysis cohort, standardized biomarker, and outcome defined prior to data linkage. Patients were eligible if N-, HR+, HER2- (by RT-PCR), had no prior malignancy, were 40-85 years of age, and were diagnosed between Jan 2004 (Oncotype DX available in Jan 2004) and Dec 2011 (SEER survival analysis complete through 2012). BCSS was defined as previously described and assessed rigorously (Howlader et al, JNCI 2010). Oncotype DX Recurrence Score results were provided to SEER as mandated by their registry operations. Analysis by treatment was interpreted in the context of the lack of randomization and well known limitations of registry reporting of chemotherapy (CT) treatment (Noone et al, Medical Care 2014). Results: Among 169,158 eligible patients, 38,568 (23%) had a Recurrence Score (RS), increasing from 2% of 2004 diagnoses to 35% of 2011 diagnoses. Patients with RS had median age of 57 yr, were 99.4% female, 84% white, 29% grade 1 and 54% grade 2, 25% 1cm or less and 53% between 1 and 2cm. Median follow-up was 39 mo with 8,239 patients having &amp;gt;5 yrs follow-up. Among low risk RS &amp;lt;18 (N=21,023), intermediate risk RS 18-30 (N=14,494) and high risk RS ≥31 (N=3,051) patients, chemotherapy use was reported in 7%, 34%, and 69%, respectively. 5-year BCSS (with 95%CI) are provided in Table. Continuous RS was significantly associated with BCSS unadjusted (p&amp;lt;0.001), and after adjusting for age, grade, and tumor size (p&amp;lt;0.001), and when stratified by treatment (p&amp;lt;0.001). Conclusions: 5 yr BCSS outcomes are excellent (99.6%) in the over 21,000 patients with low RS disease. As expected, high RS disease is associated with lower 5 yr survival despite addition of chemotherapy. More rigorous ascertainment of treatment is planned to draw conclusions regarding chemotherapy treatment benefit. Analyses that examine test utilization as well as annual survival updates to obtain longer term event rates will be important to gain additional insights into patient subgroup outcomes that can be characterized by large population-based genomic studies. RS&amp;lt;18RS 18-30RS≥31 NBCSS (95%CI)NBCSS (95%CI)NBCSS (95%CI)Analysis all pts2102399.6 (99.4-99.7)1449498.6 (98.3-98.9)305195.6 (94.4-96.6)Analysis by CT reported No/Unknown CT1955499.6 (99.5-99.7)957098.6 (98.2-98.9)93694.0 (91.1-96.0)Yes CT146999.3 (98.4-99.7)492498.6 (98.0-99.0)211596.4 (95.0-97.4) Citation Format: Shak S, Petkov VI, Miller DP, Howlader N, Gliner N, Howe W, Schussler N, Cronin K, Baehner FL, Penberthy L. Breast cancer specific survival in 38,568 patients with node negative hormone receptor positive invasive breast cancer and oncotype DX recurrence score results in the SEER database. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-01.

P002. Single-institution experience with an under age 40 symptomatic breast clinic

P002. Single-institution experience with an under age 40 symptomatic breast clinic

P001. Rural-urban differences in screening mammography uptake in Australia and Scotland

P001. Rural-urban differences in screening mammography uptake in Australia and Scotland

Comparison of the intermediate risk 21-gene recurrence score (RS) with the 70-gene signature (GS) as a continuous variable, Magee equations, and Adjuvant! Online (AOL).

47 Background: Multigene assays and risk-prediction models are used to provide prognostic information in the management of patients with estrogen receptor positive (ER+) lymph node negative (LN-) breast cancer (BC). Some have predictive utility in determining the value of chemotherapy added to endocrine therapy. We previously reported a mix of high and low risk 70-GS within the intermediate risk 21-gene RS. The Magee equations provide an estimate of the 21-gene RS using standard pathological findings. AOL provides a 10-year risk of BC recurrence or death. The objective of this study is to evaluate correlations between the 70-GS as a nondichotomous continuous variable, the Magee equations, and AOL within patients (pts) with 21-gene intermediate RS. Methods: The 70-GS as a continuous variable (highest risk of -1 to lowest risk of +1) was obtained on all consecutive ER+LN- BC cases with an intermediate 21-gene RS at Loyola U Med Ctr from 1/2005 to 9/2012. AOL recurrence risk and the Magee equations were calculated from clinical-pathologic findings. Pearson pairwise correlations among all four recurrence measures were generated. Results: Results of the 70-GS as a continuous variable and the 21-gene RS were available in 89 cases. A higher risk 70-GS correlates with a higher 21-gene RS (r = -0.31; p = 0.003). A higher risk of recurrence as estimated by AOL is associated with a higher 21-gene RS (r = 0.22; p = 0.036), higher Magee equation 1 (r = 0.36; p = 0.001) and 2 (r = 0.32; p = 0.004), and a higher risk 70-GS (r = -0.40; p &lt; 0.001). Magee equations 1 and 2 are statistically correlated to the 21-gene RS (r = 0.24; p = 0.028 and r = 0.23; p = 0.036 respectively), but not to the 70-GS (p = 0.064 and p = 0.057 respectively). Magee equation 3 is not statistically correlated with 70-GS, 21-gene RS or AOL. Conclusions: There is a continuum of highest to lowest risk 70-GS among LN- ER+ BC within intermediate risk RS. The prospective PROMIS study will assess if the 70-GS adds clinical utility regarding adjuvant therapy choice for these pts.

The influence of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in stage I-II estrogen receptor-positive breast cancer: Experience at a single center with a uniform treatment policy.

660 Background: The 21-gene assay (OncotypeDx) recurrence score (RS) has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of benefit of chemotherapy in estrogen receptor (ER)-positive breast cancer. Published data on the impact of the assay on clinical practice is limited. We analyze the influence of the RS on decision making in 135 patients seen in a single practice with a unified treatment policy. Methods: Patients with stage I and II breast cancer, ER-positive, Her2-negative who had no contraindications to chemotherapy were eligible. Clinical and pathologic data were recorded, as was the recommendation on adjuvant chemotherapy both before and after obtaining the RS. The test was performed by Genomic Health (Redwood City, CA, USA) on paraffin imbedded tissue from surgical specimens or biopsies. Our treatment policy was to give adjuvant chemotherapy for high risk RS (> 30), endocrine therapy alone for low risk RS (< 18), and for intermediate risk RS (18-30) to decide based on classical clinicopathologic features. Results: From 2/2006 to 6/2009 RS was obtained on 135 patients, including 3 males. Median age 58 (range 33-75). Histologic grade: low 36 (26.7%), intermediate 82 (60.7%), high 7 (5.2%), undetermined 10 (7.4%). Node-negative: 115 (85.2%). RS results: median 19 (range 1-57). RS risk: low 70 (51.9%), intermediate 50 (37%), high 15 (11.1%). Prior to RS result, 64 (47.4%) were recommended for chemotherapy, while after RS result 50 (37.0%) were recommended for chemotherapy. Of the 34 (25.2% [95%CI 17.9-32.5]) patients for whom recommendation was changed, 10 (7.4%) were changed to chemotherapy, and 24 (17.8%) were changed to endocrine therapy. Recommendation was unchanged in 101 (74.8% [95%CI 67.4-82.1%]). RS was independent of T stage, Ki67, and ethnic group. There were insufficient cases of high grade to evaluate correlation with grade. Conclusions: The 21-gene RS, when applied in a consistent manner in early stage breast cancer, changes the treatment plans in one quarter of patients tested. No significant financial relationships to disclose.

The Effect of Oncotype Dx® Recurrence Score on Treatment Recommendations for Patients with Early Stage Estrogen Receptor Positive Breast Cancer.

Abstract Background: Current guidelines recommend administration of chemotherapy for patients with breast carcinomas &amp;gt;1 cm in size, with consideration for patient age, comorbidities and tumor grade. However, it is unknown which patients actually benefit from therapy and overtreatment of a significant proportion of patients is a major concern. We investigated the impact of the Oncotype Dx® Recurrence Score (RS) on chemotherapy recommendations in early stage estrogen receptor (ER) positive breast cancer patients.Methods: We selected 154 patients with early stage ER positive breast cancer and available RS for the study. Clinicopathologic data, including age, menopausal status, tumor size, type, grade, mitotic activity, presence of lymphatic invasion, nodal status, hormone receptor and HER2 status on all patients were provided to four surgical oncologists, four medical oncologists and three pathologists, specializing in breast cancer diagnosis and management. Assuming that all patients were in good general health and would receive endocrine therapy, participants were asked whether they would also advovate adjuvant chemotherapy based on clinicopathologic data with and without knowledge of the RS, and to provide the three salient clinicopathologic features on which their recommendations were based. Changes in recommendations of participants following inclusion of RS data were compared.Results: Based on RS results, 95 (61.7%), 45 (29.2%) and 14 (9.1%) tumors were of low (RS &amp;lt;18), intermediate (RS 18-30) and high (RS ≥31) risk, respectively. The results are summarized in Table 1. Assuming that the hypothesis previously put forward that patients with low to intermediate risk RS are not likely to benefit from chemotherapy, 82.3 ± 1.3% (75.5 - 89.0%) and 69.0 ± 6.9% (5.9 - 85.7%) of patients for whom chemotherapy was recommended by the participants would be "overtreated" without and with the use of RS results (p = 0.0322). No statistically significant difference was found among surgeons, medical oncologists and pathologists. Participants ranked patient age/menopausal status, hormone receptor status and tumor stage/nodal status to be the most important features when recommending chemotherapy.Conclusions: Although current recommendations for adjuvant chemotherapy for early stage ER positive breast cancer patients are largely in line with published guidelines, inclusion of RS alters recommendations in about 25% of cases. While medical oncologists recommended chemotherapy more frequently compared to surgeons and pathologists, they were more likely to change recommendations in light of RS results.Table 1. Summary of results SurgeonsMedical oncologistsPathologistsp* Mean ± SEMRangeMean ± SEMRangeMean ± SEMRange Chemo without RS (%)29.2 ± 1.824.0 - 31.859.0 ± 5.046.8 - 70.846.8 ± 3.741.6 - 53.90.0156Chemo with RS (%)27.0 ± 5.611.0 - 36.438.6 ± 9.517.5 - 63.644.4 ± 5.833.8 - 53.90.1794No change (%)75.3 ± 7.054.5 - 85.766.7 ± 6.851.3 - 83.885.9 ± 6.478.6 - 98.70.3682Add chemo (%)11.2 ± 4.13.2 - 22.76.5 ± 1.93.2 - 11.75.8 ± 3.20.6 - 11.70.6882Avoid chemo (%)13.5 ± 3.94.5 - 22.726.8 ± 7.94.5 - 41.68.2 ± 4.50.6 - 16.20.2186*Kruskal-Wallis test Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4058.

Complementary Value of the Ki-67 Proliferation Index to the Oncotype DX Recurrence Score

Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen receptor-positive breast cancer, which is expressed as the recurrence score (RS). Studies have shown that patients with a high-risk RS will most likely benefit from adjuvant chemotherapy, but there is no proven advantage for patients with a low-risk RS who still face an average recurrence risk of 7%. In this study, the relationship between the RS and the cell cycle-related antigen Ki-67 was assessed in 32 breast carcinomas and evaluated for a potential association. Comparison of the RS with tumor type, grade, and the Ki-67 proliferation index (PI) revealed an overall concordance. However, some tumors with a low RS revealed a surprisingly high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas that recur. Therefore, the authors propose a combined evaluation of the RS and Ki-67 PI to identify tumors with high recurrence potential from the low-risk and intermediate-risk RS groups.